MT Host + Genomics Flashcards

Question

# Intro to Genome Evolution advantages of alternative splicing

Answer 1

* major role in evolution of new gene functions/new proteins * existence of introns and genes being in 'pieces' of exons and introns allow alternative splicing of same gene into different proteins depending on mRNA splicing * doesn't require completely new synthesis of an exon, one copy is sufficient * hence saves energy to copy exon

Answer 2

2 rounds of whole genome duplication in animals, specifically in vertebrate ancestry * hypothesis that vertebrates originated after 2 rounds of WGD

Answer 3

* Evolution by gene duplication = major source of new genes and evolutionary novelty * Involves duplication of individual denes and sometimes entire genomes (like the fungi example) * WGD - whole genome duplication in animals thought to have driven originated of vertebrates * WGD much more common in plants and fungi

Answer 4

*** Once a gene is duplicated, some functional redundancy is created, reduces purifying selection and allows the two copies to accumulate mutations and diverge in function.** * Often duplicated copies perform very similar roles, but in a slightly different way * as was the case for Adh and jingwei genes in Drosophila The two copies of a gene can specialise (and be optimised) to work in different tissues or in slightly different ways.

Answer 5

1. sub-functionalisation 2. neo-functionalisation 3. specialise and optimsed to work in different tissues or via different mechanisms 4. can also be selected against and be removed

Answer 6

* evolution of trichromatic color vision in primates * ancestral state is dichromatic, because ancestors were nocturnal and color vision wasn't necessary for that * primates are diurnal (work in day) and rely on cokor vision to find ripe fruits, hence this trait is more useful *** Evolution of trichromatic colour vision in primates occurred as a result of gene duplication: the L- gene (for Long wave length) was duplicated and the resulting genes diverged little bit, resulting in L- and M-genes (for Medium wave length).** * after gene duplication which created L and M opsin genes, the duplication copies diverged to acquire different spectral sensitivities * In humans spectral sensitivity is relatively poor, in comparison to bees and birds which civer nearly equally the entire visible ligjt wavelength * in birds with better vision, they have evolved to have high spectral sensitivity across all wavelengths, and evolved a new VS opsin gene ## Footnote 2010 paper

Answer 7

1. gene duplication 2. genome duplication 3. spread of transposable elements ONLY DELETION causes downsize in genome, frequency and size of deletion determine eficiency of genome downsizing

Answer 8

* genome expansion cause genome sizes vary over several orders of magnitude. * Does not mean that the bigger genomes contain more genes and could encode for more complex organisms: *** Larger genome IS NOT EUQAL to more genes DOES NOT EQUAL TO more complexed organisms** * Proof: the genomes of various flowering plants (that have relatively similar ‘design/function’ and complexity) vary over three orders of magnitude, suggesting that the size of the genome has little to do with organism complexity.

Answer 9

Proof: the genomes of various flowering plants (that have relatively similar ‘design/function’ and complexity) vary over three orders of magnitude, suggesting that the size of the genome has little to do with organism complexity. * also the C paradox shows this as well, eukaryotic genome size is not linearly correlated to its number of genes, this is because the existence of junk DNA

Answer 10

* The number of genes and the genome size show good correlation in viruses and prokaryotes, correlation is much weaker for eukaryotes – the so called “C-value paradox”.

Answer 11

* The reason for this is the abundance of non-coding DNA in eukaryotic genomes. * More DNA doesn’t mean more genes in eukaryotes due to existence of introns

Answer 12

range very quickly across multiple species from 200mya. shows the variavility of the genome even in closely related species. Also showing genome size change = changes in function hugely ## Footnote Organ et al., 2007

Answer 13

Genome sizes for extinct animals was measured from the size of cells inside the bones – the larger the genome, the larger the cell. For dinosaurs the size of the cells was measured from the size of pores in the bones. This revealed that genomes of dinosaurs and mammals are relatively large, while bird genomes appear to have been downsized, possibly as an adaptation to faster lifecycle and flight. ## Footnote organ et al., 2007

Answer 14

the size of genome had structural roles to maintail cell size and cell shape in animals large cell size and genome for dinosaurs and mammals which are physically larger and have bigger cells, and cell size and genome are smalle for birds (which are smaller)

Answer 15

* Transposable elements are a major component of most genomes: * >50% of humans and > 70% of wheat genome is comprised of various TE, * Activation of jumping gene transposable elements can quickly cause the double the genome size and cause increase of genome sizes very quickly * Activation of a single family of TE can lead to rapid increase of genome size, as was reported for S.latifolia and cotton * Example 1: Silene latifolia: the spread of a TE (SIOgr1) family ~5mya increased it’s genome size from 2Gb to 3.5Gb (comparing S.latifolia and its most recent relative S.vulgaris) * Example 2: Gossypium (cotton) family: The four fold difference in genome size between closely related species: from 880Mb in G.raimondii to G.exiguum (2460Mb) * because of the spread of the TE family Gorge 3 (which increased from 61Mb in G.raimondii to 831Mb in G.exiguum) ## Footnote Filatov et a;., 2008 ; Hawkins et al 2009

Answer 16

activation of TE leads to rapid increase in genome size in: 1. Example 1: Silene latifolia: the spread of a TE (SIOgr1) family ~5mya increased it’s genome size from 2Gb to 3.5Gb (comparing S.latifolia and its most recent relative S.vulgaris) 2. Example 2: Gossypium (cotton) family: The four fold difference in genome size between closely related species: from 880Mb in G.raimondii to G.exiguum (2460Mb); because of the spread of the TE family Gorge 3 (which increased from 61Mb in G.raimondii to 831Mb in G.exiguum)

Answer 17

* **The frequency and size of deletions occurring in the genome determines how efficient is genome downsizing. ** * A study analysed and compared the frequency and size of deletions occurring in a small genome of Drosophila and a very large genome of cricket Laupala. * This showed that Drosophila has frequent deletions and many of them are relatively long (>16 nucleotides). * On the other hand, the cricket had fewer deletions and most of them very short. * This study demonstrated that half-life of a piece of junk DNA in Drosophila is only 14 million years, while in the cricket it is over half a billion years * effectively junk DNA is never removed from Laupala genome. * This is likely to be the reason why these species have so different genome sizes. * In constant process of adding and removing genes, and rate and size of removing and adding is all varable * From large genome junk DNA is almost never removed

Answer 18

Maybe bcuz of their large genome, the junk DNA doesn’t have enough negative selection pressure to remove it. Too much DNA to process, so not worth removing it from evo perspective?? UNSURE THO!!

Answer 19

**Buchnera** * Buchnera is a mutualistic intracellular symbiont of aphids. * Their association began about 200 million years ago, with host and symbiont lineages co-evolving in parallel since that time. * During this coevolutionary process, Buchnera has experienced a dramatic decrease of genome size (from ~4Mb to ~0.5Mb genome), retaining only essential genes for its specialized lifestyle – essentially majority of all biochemical pathways are removed * for better adaptation as an intracellular symbiont, and doesnt require processes which it can rely on host for * Lost because selection is not keeping them intact * Strong selection for non-essential genes due to symbiotic lifestyle (intracellular) ***Miochondria** * similarly, mitochondria as a symbiont in endosymbiosis theory, also became a symbiont * mitochondria has a super reduced genome of only 16kb long, having essential mitochondria specific genes

Answer 20

* The comparison of genomes of two buchnera species that diverged 50 million years ago revealed very similar gene content, * Buchnera has undergone genome reduction a long time ago and little has changed since then * it is effectively in genomic static, with no signs of further genome reduction. * genome unlikely to be reduced further * Maybe due to the remaining ones are VERY ESSENTIAL to life and further reduction won’t have any more evolutionary benefits for its current lifestyle and environment

Answer 21

homologous recombinantions between autosomes and original sex chromosomes, this causes multiple sex chromosomes,

Answer 22

a pair of autosomal chromosomes acquired sex determining genes, and becomes non-recombining through increasing mutations which prevent them from recombining

Answer 23

alternatie splicing exon shuffling

Answer 24

divergence in functionality and results in sub functionalisation or neofunctionalisation

Answer 25

IT DOESNT MEAN MORE COMPLEXED ORGANISM OR MORE PROTEINS but it can be related to cell sizes and life-strategy of organisms

Answer 26

when activated, they can increase genome size very rapidly by creating lost of junk DNA

Answer 27

increases: duplication, TE, ...etc Deletion rate depends on frequency, size of genome, and selection pressure. Larger genomes often is harder to remove junk DNA

Answer 28

- Genome reduction in mitochondria and symbionts like Buchnera are extreme examples, as their genomes have been reduced too an extreme amount due to their intracellular and symbiotic lifestyle

Answer 29

* Addresses questions about recent evolution * Where did humans originate? * When have humans spread across the world? * While spreading, have humans been adapting to a diverse set of environmental conditions? * Have humans interbred with other closely related species, such as Neanderthals?

Answer 30

MtDNA more useful than nuclear DNA because it is non-recombining in humans mtDNA: High copy number per cell, small genome (16kb), High mutation rate, No recombination easy and cheap to research/sequence *** mtDNA is not recombining and hence can build phylogenies within species, consistent trees**

Answer 31

MtDNA more useful than nuclear DNA because it is non-recombining in humans shows the 'maternal' side pof the story mtDNA: High copy number per cell, small genome (16kb), High mutation rate, No recombination easy and cheap to research/sequence *** mtDNA is not recombining and hence can build phylogenies within species, consistent trees**

Answer 32

* African genetic diversity significantly higher than others * Conclusion of this study (building phylogenetic tree from different races) resulted in that the root of the mtDNA phylogeny is in Africa * Consistent with the fact Africa has the biggest genetic diversity * Whole genome mtDNA comparisons gave same conclusion (using molecular clock) LIMITATION: selective sweep of a single strongly advantageous mutation would produce same appearance, might not neccessarily be migration from africa

Answer 33

* non-recombining * independent evidence about the human history as it is unlinked to mtDNA. * paternally inherited and allows us to look at the ‘male history’, * Y- based phylogeny is consistent with mtDNA. It also has a root in Africa and African lineages are most diverse * Supports previous hypothesis

Answer 34

* However using austosomes (nuclear genes) is a problem as they do recombine * Difficult to form the phylogenetic tree * But Principle Component Analysis (PCA) can be used to analyse polymorphisms in autosomal DNA sequences. * Recombination leads to independence of evolutionary histories of different genes hence more unique data * provided further support to the idea that Africa is the source of all modern humans

Answer 35

- Timescale: * Nuclear genes – deeper phylogenies explore human ancestry * mtDNA would only give us the most recent common ancestor for humans, but nothing further due to the single mitochondrial lineage

Answer 36

* lower recombination rate, means stronger hitchhiker effect, neighbouring genes of the selected gene is more likely to stay * hence The spread and fixation of an adaptive allele results in loss of genetic variation around the loci of the target allele (the allele around it will also be preserved along w the advantageous allele) * Size of the region affected by selection sweep depends on recombination rate * i.e in Y chromosome where no recombination occurs: entir chromosome will lose genetic variation after an advantageous (adaptive) allele is fixed in the chromosome * i.e If frequence recombination: only a short region around the adv allele will be fixed after the adv allele is fixed

Answer 37

The fixation index (FST) is a measure of population differentiation due to genetic structure FST is the proportion of the total genetic variance contained in a subpopulation relative to the total genetic variance, ranges from 0-1 low Fst means a lot of gene flow and breeding and connectivity between subpopulations, keeping it similar to the overall genetic variance high Fst above 15% means that this sub-division is differentiated

Answer 38

After 1st selective sweep, it leads to surrounding genes of the adv allele to decrease in genetic variation as new mutations accumulate, genetic variation in that area will recover due to new mutations arising causing more genetic diversity/variation.

Answer 39

using a statistics called Tajima's D, this is because ALL new mutations are at very low frequencies, this bias allows them to be detected by the stats

Answer 40

Adaptation to contrasting conditions (e.g. high/low altitude) leads to spread and fixation of different locally adaptive alleles in the populations. this is a typical footprint of local adaptation to identify genetic variants which are evolving under this type of selection pressure

Answer 41

Fst statistic = (Ht - Hs)/Ht Ht = total heterozygosity across all populations, and Hs is heterozygosity within populations

Answer 42

Identifying local adaptation can be done through population differentiation to different environments which leaves a ‘signature’ as their genetics between the 2 diff environments would be different,

Answer 43

In a study of Han chinese and Tibetan population differentiation, the EPAS1: has the strongest and most obvious differentiation to other genes: it has a very high Fst. This means that this gene has the strongest signal for population differentiation and locally adapted gene EPAS1. this gene EPAS1 in tibetans are ery divergent from other hapotypes in other human populations, and was revealed to have been inherited from Denisovan genome, during early interbreeding. Even if early interbreeding was rare, the provided genetic diversity can be very beneficial and advantageous and can spread through natural selection

Answer 44

It suggests that most evolutionary changes at the molecular level (such as changes in DNA or protein sequences) and genetic variation/diversity are not caused by natural selection acting on advantageous traits. Instead, these changes are the result of random genetic drift of mutant alleles that are neutral. rare beneficial mutations occur and selective sweep the occurs rapidly to fix these beneficial mutations.

Answer 45

a type of natural selection where genetic diversity is maintained within a population. Unlike directional selection, which favors a single allele and can lead to a decrease in genetic diversity over time, balancing selection ensures that multiple alleles are preserved at a particular gene locus.

Answer 46

1. Heterozygote Advantage (Overdominance): when being a heterozygote (hence having 2 diff allele copies) give you adv. For example, in africa, adv to have heterozygote sickle cell anemia (Hbs/HbA), as it protects you from malaria, and is not completely fatal 2. Frequency-Dependent Selection: fitness of a phenotype depends on its frequency relative to other phenotypes in the population. There are two types: positive frequency-dependent selection, where the fitness of a phenotype increases with its frequency, and negative frequency-dependent selection, where the fitness of a phenotype decreases as it becomes more common. Example: coloration to avoid predation. If one coloration becomes popular, predator will recognise and predate more of the same color. Hence in this case fitness of phenotype decreased as phenotype becomes common. Hence allows multiple alleles for colors to be present in population 3. Disruptive selection: Not neccessarily balancing selection., but can contribute to maintaining multiple alleles

Answer 47

1. all mutations are rare to start with 2. if adv mutation occured which was dominant, then selective sweep may occur quicker 3. if adv mutation was recessive, it would take much longer as it would have to meet another recessive first. 4. if they were linked to another dominant beneficial allele, it can spread quicker through hitch-hiking 5. or spread wuicker through migration, genetic drift, funder's effect...etc

Answer 48

Reconstructing patterns of shared ancestry among organisms (within or between species), really about ancestry

Answer 49

Taxonomy: describing, naming, identifying and classifying species, grouping organisms into groups

Answer 50

the evolutionary history, ancestry and relationships between groups of organisms

Answer 51

we combine phylogenetics and taxonomy together to create phylogenies. * modern taxonomy classification use phylogenetics techniques too * phylogenetic trees: evolution of phylogenies

Answer 52

DNA sequence date, useing DNA sequence of cytochrome c phylogeny to build phylogeny trees by looking and comparing mutations

Answer 53

similarity essentially. the state of having the same or similar relation, relative position, or structure: many proteins show homology across their whole length | a region of homology with another gene.

Answer 54

because when comparing organisms in terms of evolution, their characteristics can either be homologous or analogous. Characteristics of organisms are homologous if they are similar and have descended from a common ancestor. Characteristics are analogous if they are similar but have descended from different ancestors. i.e Bird and bat wings are homologous when considered as forelimbs, but analogous as wings.

Answer 55

homology, by comparing similarities and differences

Answer 56

Using molecular sequences which contain information about evolutionary history to build phylogenetic trees. Information is often hidden, or fragmented in DNA hence modern phylogenetics use stats, and technology to try recover and interpret information from DNA about phylogeny and evolutionary history

Answer 57

1. Homologous sequences: sequences have a shared common ancestry, and are related. Very broad term. umbrella term for sequences that are related by descent from a common ancestral sequence. 2. Orthologous Sequences: In different species, occurs ater a speciation event. They are sequences which were inherited from same ancestor, but then they speciated and diverged. Ortholog genes in different species have not undergone gene duplication, and remain tio have similar function 3. Paralogous sequences: sequences of genes of 2 diff species which are related through gene duplication events in the same genome. Evolved new function, new gene from old gene.

Answer 58

**Homologous** is the broad category indicating genetic relatedness due to common ancestry. **Orthologous** genes diverge after a speciation event, leading to similar genes in different species. **Paralogous** genes result from gene duplication within the same organism, potentially leading to genes with new or specialized functions.

Answer 59

* Molecular characters have many advantages over morphological ones: * Very common * Objective, easy to quantify * Available when morphology is uninformative (micro-organisms) * Cheap, fast * Can be obtained without specialist training However phylogenetics has many cases where morphological and molecular data initially disagreed, andthis led to progress of phylogenetics

Answer 60

unavailable in extinct species or fossils

Answer 61

bacteria, archaea and eukarya phylogenetics tree was constructed using rRNA sequences. 163 rRNA and 18srRNA

Answer 62

1. The Placement of Whales: morphology like marine, but molecular data = mammals 2. funghi classification: morphology = plant like, molecular = more related to animals 3. protists = grouped together due to morphological characteristics of being 'animal-like' and 'plant- like', but molecular data revealed = paraphyletic lineages were included. Hence still very much a 'dump' classification

Answer 63

1. transition mutation: purine to purine, pyramidine to pyramidine, A-G, C-T, quite common 2. transverse mutations: purine to pyramidine, rare (less freq than transitions) 3. silent/synonymous mutations: encoded amino acid is unchanges, 70% in 3rd position of codon dont change amino acid sequence at all (redundancy) 4. replacement/non-synonymous mutations: encoded amino acid is changed (can cause selection pressure) 5. insertion: addition of one or more nucleotides to a sequence 6. deletion: removal of one or more nucleotides form a sequence 7. indels cause nonsense mutations, replacemnt can cause missense

Answer 64

1. First obtain molecular sequences 2. using alignment methods, align the sequences correctly 3. then using sequence evolution models, to work out the genetic distance between the sequences 4. then using phylogenetic methods, ypu can build a evolutionary tree where time scale - genetic distance 5. then using molecular clock models to build an evolutionayr tree, timescale = years 6. then either using coalescent thoery: to get population level process, or macroevolution models to get species level processes

Answer 65

**population level processes** changes to population of single species over time * natural selection * genetic drift * gene flow * mutation * sexual selection **species level processes**changes that affect the emergence, evolution, and extinction of species. * speciation * extinction * adaptive radiation * coevolution * hybridization

Answer 66

1. BLAST can be used for MSA and general matches 2. but other algorithms such as clustal and muscle may be better 3. Global alignment

Answer 67

Because there are multiple ways to align and compare sequences. Depending on the way of alignment, the interpretation of the sequences will be different, giving potential incorrect evolutionary histories

Answer 68

* molecular sequence alignment is based on the concept of positional homology. * nucleotides or aa have positional homology if they exist at equivalent positions in their compared sequences * A set of nucleotide or amino acid sequences is converted into an alignment by proposing positional homologies for each site. * There are many possible ways to align and compare a sequence

Answer 69

1. multiple sequence alignment (MSA): alignment of three or more sequences of similar length. 2. Global alignment: a method used to align two sequences from beginning to end, maximizing the number of matches and minimizing the number of mismatches and gaps across the entire length of the sequences. It's a type of pairwise sequence alignment.

Answer 70

1. for multiple sequence comparisons 2. helps iidentify conserved sequences across multiple organisms, which may be indicative of functional or structural importance. 3. understanding phylogenetic relationships, predicting the function of unknown proteins, and identifying conserved motifs. Challenge: as number of sequences increase, more computationally challenging to align Example: CLUSTAL and MUSCLE

Answer 71

* The goal is to find the best possible alignment that includes all characters from both sequences, which is particularly useful for comparing sequences of similar length and identifying overall similarities and differences. * Needleman-Wunsch algorithm, systematically compare all possible alignments and select the one with the highest score based on a scoring matrix.

Answer 72

1. MSA is used to align three or more sequences and is essential for analyzing conserved regions across multiple sequences, while global alignment is designed for comprehensively aligning two sequences from start to finish. 2. MSA is widely used in evolutionary studies, functional annotation, and identification of conserved motifs across multiple sequences. Global alignment is more suited for comparing two sequences in their entirety, such as when determining the overall similarity between two genes or proteins from different species. MSA pros: * useful in evolution study of multiple organisma and phylogenetic relationships * identify conserved regions MSA cons: * Gap Penalty Ambiguity: length of indels may affect how valid it is, especially in low similarity regions * highly divergent and varied lengths can be difficult to align * computational limitations: if too many sequences GA pros: * Needleman-Wunsch, which systematically explore all possible alignments to find the optimal one. * Complete Alignment: It aligns two sequences from beginning to end, useful for closely related sequences of similar length. * Scoring System: The use of a scoring system (for matches, mismatches, and gaps) allows for quantifiable comparison of alignments, making it easier to assess the quality of the alignment. GA cons: * only pairwise, so less suited for evolutionary and phylogeny studies * varying lengths with large indels are difficult to compare and align

Answer 73

by assigning a different “cost” to each type of sequence difference (transitions, transversions, insertions, deletions etc). Using algorithms calculate costs, each possible alignment therefore has a total cost. Then identify the algorithm with the lowest cost

Answer 74

**clustal** * clustal is algorithm for MSA * first use scoring system for pairwise comparison between sequences, then creating a guide tree from these sequences and making adjustments with pairwise and MSA considerations * can align varying lengths and divergence (as long as not too diverged sequences **MUSCLE** * good for large datasets for high speed and accuracy * 3 step model

Answer 75

1. if too diverged and low similarity, less accurate 2. varying lengths can be dificult 3. large dataset/too many sequences = computational complexity 4. too large/too many indels can be difficult and lead to low accuracy

Answer 76

* to identify if they have undergone convergent or divergent evolution, and how many substitutions and mutations occured at each nucleotide/amino acid position * to measure the evolutionary process of sequences, not simply compare their differences and number of mismatch * also need to consider and calculate if they have gone through multiple substitutions and convergent evolution from A-C-A instead of A-A (p-distance)

Answer 77

**When divergence is low, the observed number of changes is similar to the true genetics distance** **When divergence is high, the observed number underestimates the true genetic distance.**

Answer 78

same position of genome having multiple mutations over time, showing convergent evolution

Answer 79

p-distance= Number of differing positions/ Total number of positions compared proportion of differences, measure of genetic distance in evolutionary biology. It quantifies the genetic difference between two sequences (DNA or protein sequences) by calculating the proportion of sites (nucleotide or amino acid positions) at which the sequences differ. Limitations: The p-distance can underestimate the true evolutionary distance between sequences because it does not account for multiple substitutions at the same site (back mutations or parallel mutations). For sequences that are highly divergent, use algorithms that account for multiple hits

Answer 80

* it is a mathematical model which aims to represent the processes of mutation and natural selection at the molecular level. It considers the probabilities of changes from one nucleotide (A, T, C, or G) to another across a phylogenetic tree. * describes the rate of nucleotide change from one to another over time

Answer 81

* Estimating Divergence Times: By calculating the rates of nucleotide substitutions, we can estimate how long ago two species or sequences diverged from a common ancestor. * Understanding Evolutionary Forces: These models can provide insights into the forces shaping genetic evolution, such as mutation rates, selection pressures, and genetic drift. * Evolutionary Inference: By understanding genetic distances, we can construct evolutionary histories to.

Answer 82

*assign relative rates of different types of mutations * Jukes-Cantor (JC) Model: The simplest model, assuming that all substitutions occur at the same rate and each nucleotide has an equal chance of changing into any other nucleotide. Assumes all mutations occur at same rate * K2P model: Also quite simple, introduces 2 different rates for transition and transversion mutations * HKY model: more advanced. More realistic model. takes into account of unequal base frequencies. Also it distinguishes different rates between pyramidine to pyra, and puri to puri. as well as if its pyuri to pyri, or pyri to puri. * The geneal Time reverisble (GTR) model: The most general and complex model, allowing for different rates for all possible changes between nucleotides and different equilibrium nucleotide frequencies. GTR can encompass the simpler models as special cases. Supposes 6 different mutation rates for each case.

Answer 83

Realistic models include the relative frequency of each nucleotide, i.e if lots of As, more likely to see A mutate than T mutate (looks at percentage mutation rather than abundance) so far GTR is most flexible and most complex, as it supposes 6 diff mutation rates, and takes into account of frequencies of bases.

Answer 84

**JC models: ** * Pros: easy to use, good if the dataset of sequences are limited and when the frequency of bases are largely similar and supposed similar substitution rates are also somewhat the same. * Cons: over-simplification of the reality of mutations, in large datasets not very realistic and doesn't reflect evolutionary history if the rates are different **GTR model** * Pros: reflects the evolutionary histories more realistically, more flexible and complex. More adaptabiloty for different substitution rates * cons: overfitting: may over-interpret on noise data or small datasets. Requires mor computational complexity

Answer 85

* nucleotide models for DNA/RNA seqs, aa models for protein seq * These models are used to study the evolution of protein-coding genes by describing how amino acids change over evolutionary time. * calculating the probabilities of one amino acid being replaced by another in a protein sequence over time. * These models account for the fact that some amino acid changes occur more frequently than others due to factors like the physicochemical properties of the amino acids and the functional constraints of the protein. The models define rates of substitution for all possible pairs of the 20 amino acids.

Answer 86

Understanding these changes helps scientists infer protein function, evolutionary relationships, and the dynamics of molecular evolution.

Answer 87

* These models account for the fact that some amino acid changes occur more frequently than others due to factors like the physicochemical properties of the amino acids and the functional constraints of the protein. The models define rates of substitution for all possible pairs of the 20 amino acids. * hence it is a 20x20 matrix, for all 400 possibilities * These rates are obtained from large surveys of protein variation (not from your particular data set). * Equilibrium Frequencies: Most models also consider the equilibrium frequencies of the amino acids, which represent the expected frequencies of each amino acid during evolution

Answer 88

* JTT Model: model uses a large database of known protein sequences to deduce rates. It adjusts the substitution rates and amino acid frequencies based on empirical data, making it useful for a wide range of evolutionary distances. * These rates are obtained from large surveys of protein variation (not from your particular data set).

Answer 89

**amino acid models** * Pros: functional evolution of proteins, more suitable to study highly diverged protein sequences - can cpature more info when nucleotide saturation (multiple hits) occurs. More simple analysis looking at a larger scale rather than small synonymous changes in nucleotide.Directly understand selection pressures at a phenotypic/protein level * Cons: Loss of Information: losing information about synonymous changes (which don't alter the amino acid sequence) and potentially informative patterns in codon usage or RNA secondary structure. **Nucleotide models** * Pros: Detailed Evolutionary Insights, including synonymous mutations, which can be crucial for understanding selective pressures at the molecular level. Can construct higher resolution phylogenetic tree, when the protein models don't produce detailed enough evolutionary differences * Cons: Saturation Issues: For highly divergent sequences, saturation—where multiple hits occur—can make nucleotide models less effective over long evolutionary timescales. Only for short time scale

Answer 90

**amino acid model**: * when focus is on protein-coding genes/phenotype selections that have experienced significant evolutionary divergence, * when interested in functional aspects of protein evolution, * or when nucleotide sequences are so divergent that saturation obscures their evolutionary history. **nucleotide models** * when analyzing closely related sequences, (identifying phylogenetic relationships between closely related species) * where synonymous changes are informative, or when studying non-coding DNA regions. **ultimately depends on whether interested in coding/non-coding, and how specific the researched evolutionary distance is, and how long/large the divergence/evolutionary history may be**

Answer 91

* assumptions lead to errors when assumptions aren't true * Evolution homogeneity: These models often assume that substitution rates are homogeneous/same across the entire sequence being studied. However, different regions of a gene or protein may evolve at different rates due to functional constraints or varying levels of selective pressure. * Independence: Another assumption is that substitutions at different sites occur independently of one another. In reality, the evolutionary process can be influenced by interactions between sites (epistasis), where the effect of a mutation at one site depends on the sequence at another site. Especially this assumption doesn't consider 3D shapes and structures of proteins * Saturation in nucleotide: multiple hits problem, can't infer long evolutionary history or hugely divergent sequences

Answer 92

Use models of among-site rate heterogeneity (usually the gamma model) where it models not every site evolves at same rate It incorporates the realistic scenario that not all parts of a sequence evolve at the same rate. Some regions might be highly conserved due to functional constraints, while others might evolve more rapidly.

Answer 93

provides a distribution of sites having different evolutionary rates. This is done by adding an extra alpha parameter, to indicate if this site has a faster or slower variation rate.

Answer 94

helps understand relationships among different species or genes and also when their divergences occurred in terms of genetic distance construct new branches and nodes on phylogenetic tree based on genetic distances/genetic changes

Answer 95

1. rooted tree: has evolutionary direction, and horizontal lines represent genetic distance 2. unrooted tree: all lines represent genetic distance, and there is no evolutionary direction

Answer 96

techniques used in evolutionary biology to infer the evolutionary relationships and history among groups of organisms, genes, or other units of biological interest. These methods aim to reconstruct the "phylogeny" or evolutionary tree that represents hypotheses about the ancestral relationships and divergence events that have led to the current diversity of life. They require other molecular information (like genetic distances) as a basis

Answer 97

1. UPGMA 2. Neighbour Joining 3. Maximum Parsimony 4. Maximum Likelihood 5. Bayesian Inference

Answer 98

* Different for different models. * UPGMA and Neighbour-Joining rely on genetic distance for algorithm to work, and hence require sequence alignment to make genetic distance and then use a matrix of genetic distances as a basis for the algorithm * others like Maximum likelihood, maximum parsimony and bayesian inference only require aligned sequences, but lther parameters have to be altered when running the algorithm * some programs can run multiples steps all together, from alignment to genetic distance to generating a tree. But choosing the best and most suitable model prior to constructing the tree is important

Answer 99

1. choosing right model based on sequences/dataset. i.e how divergent sequence is, how large data set is 2. changing the parameters when using the models 3. adding additional time estimates 4. making sure prior alignment + genetic distance estimates are accurate 5. adding in bootstrap value

Answer 100

1. being able to look at divergences and homology of species 2. evolutionary history and relatedness of species

Answer 101

* classified by different ways **Algorithmic/ distance based methods** * These methods begin with a genetic distance for each pair of sequences. A ‘clustering algorithm’ then transforms the genetic distances into a tree. * e.g .UPGMA, Neighbour-Joining (NJ) **Optimality methods** * These methods define some kind of score for each possible tree. An optimisation algorithm to find the tree with the highest score., most optimal tree * e.g. Maximum Parsimony (MP), Maximum Likelihood (ML) , Bayesian Inference **Statistical method** * These methods calculate a probability for each possible tree. They frame phylogeny estimation as a formal statistical problem * e.g. Maximum Likelihood, Bayesian Inference

Answer 102

* molecular clock is not a separate method for constructing phylogenetic trees by itself, but rather a concept or parameter that can be integrated into various phylogenetic methods. * hypothesis: genetic mutations accumulate at a roughly constant rate over time in a given genomic region. In other words, the amount of genetic change (mutations) that occurs is proportional to the time that has passed.

Answer 103

*** Strict Molecular Clock**: Assumes the same rate of mutation accumulation for all lineages being studied. This is a simpler but often less realistic assumption. *** Relaxed Molecular Clock**: Allows for different rates of mutation accumulation in different lineages. This is more complex but often more accurate, as it accounts for the fact that different species or genes might evolve at different rates. **Local Clock**: Rate varies, but is inherited, so adjacent branches have more similar rates

Answer 104

* used to estimate the time of divergence between different species or lineages based on their genetic differences, hence constructing tree * a parameter that can change genetic distances to time estimates in tree * Because of this constant rate, the molecular clock can be used to estimate the time of divergence between different species or lineages. * By comparing the genetic differences between two species and knowing the rate at which mutations accumulate, scientists can estimate how long ago their common ancestor lived.

Answer 105

* Rate Measurement: if a certain gene accumulates one mutation every million years on average, and two species differ by ten mutations in that gene, they likely diverged about ten million years ago. This can be done through measuring genetic distances * Calibration: To use a molecular clock effectively, it often needs to be calibrated with independent data, such as fossil records, geological events, or known evolutionary events. These calibrations provide reference points to determine the mutation rate. For example using a knwon divergence time of species

Answer 106

* Rate Variation: Not all genes or regions of DNA evolve at the same constant rate. Some may evolve more quickly or slowly, affecting the accuracy of the clock. * Calibration Accuracy: The accuracy of a molecular clock depends heavily on the accuracy of the calibration points used. * Evolutionary Pressures: Natural selection and other evolutionary forces can affect mutation rates, complicating the assumption of constant rates.

Answer 107

**Distance-Based Methods** (e.g., UPGMA, Neighbor Joining): * molecular clock can be an underlying assumption. * For instance, UPGMA assumes a strict molecular clock (constant rate of evolution across all lineages), which can be a limitation. * Neighbor Joining does not assume a strict molecular clock, making it more flexible and broadly applicable. **Maximum Likelihood (ML) and Bayesian Inference (BI):** * incorporate the molecular clock as an optional parameter in their models. *use "relaxed" molecular clock models, which allow for variation in the rate of mutation accumulation among different lineages. This is more realistic for many datasets. In Bayesian analysis, particularly, the molecular clock can be integrated with prior information to estimate divergence times along with the phylogenetic relationships.

Answer 108

* comparative methods involve comparing various biological traits (like anatomical, physiological, or molecular traits) across different species or groups. * These methods are used to understand the evolutionary relationships and processes that have shaped these traits. * Comparative methods can be used to test hypotheses about evolutionary processes, like adaptation, co-evolution, or the impact of environmental factors on evolution. * used to investigate evolutionary processes after tree is constructed: for example determining divergent or convergent evolution by analysing tree

Answer 109

* distance based/algorithmic methods * hence requires genetic distance in matrix and accurate alignment in advance * The distances measure how different the sequences are, which is assumed to reflect evolutionary time. * strict molecular clock is assumed, where assumes constant rate of evolution across all lineages (same rate of mutation) * constructs a phylogenetic tree by clustering taxa based on their pairwise distance. It begins with the closest pairwise distant pair of taxa and builds up the tree by sequentially adding branches. Limitations: *cannot compare for 'best' tree as this method only forms one tree. * Assumes a constant rate of evolution, which is often unrealistic. * Not as accurate for datasets where evolutionary rates vary. * not accurate for highly divergent sequences Pros: * useful for quick analysis * useful if the dataset fits assumption of molecular clock (where not much selection pressure is present, constant rate of mutation..which is unlikely)

Answer 110

* distance based/algorithmic method * hence requires genetic distance + accurate alignment * NJ builds a tree by iteratively grouping the closest pair of taxa, but without assuming a constant rate of evolution * very similar to UPGMA but without assuming a strict molecular clock Limitations: * only produces one tree so cannot ocme up with a 'more ideal' tree to compare with * Accuracy can diminish with highly divergent sequences

Answer 111

* Optimality based method * doesn't require genetic distances (so no substitution model needed), only requires alignment * MP constructs a tree by minimizing the total number of evolutionary changes (like mutations) required to explain the observed data. * It compares all possible tree topologies and selects the one with the least changes. * uses a parsimony score: the minimum number of evolutionary changes/mutations required to explain the observed changes in sequences Pros: * fast * doesnt require substitution models * Most useful when applied to morphological character data. Limitations: * Can be misled by convergent evolution (independent evolution of similar traits) * but inapplicable to fast-evolving or highly-divergent sequences. * does not specifically account for different evolutionary rates/models

Answer 112

* optimality + statistical model * most commonly used * ML evaluates different tree topologies based on the probability of observing the given data under different evolutionary models. * evolutionary models = substitution models lol * Chooses the tree that maximizes the likelihood of the observed data given a particular model of sequence evolution/substitution models * the highest probability = the best tree * the probability is calculates based on the tree topolopgy, the branch lengths of the tree (which represents genetic distance calculated by the substituion/evolutionary models), and the rate parameters of substitution models * uses relaxed clock * Tree seaching is used to dins the topology with the highest likelihood Pros: * Statistically robust; uses explicit models of sequence evolution. * Handles variable rates of evolution across lineages and sites well. * High accuracy in tree estimation. * sophisticated Limitations: * slow * Computationally demanding, especially with large datasets. * The choice of model can greatly influence the results.

Answer 113

* A tree search is used to find the tree top with the highest likelihood. **Tree Searching** 1. Exhaustive Search: * Tries every possible tree. Only feasible with small numbers of taxa. 2. Hill Climbing: * Searches through trees by iterative trial and error. * Start with one tree and try, if incorrect, try another tree * Doesn’t check all possible trees and isn’t guaranteed to find the optimal one.

Answer 114

* optimality and statistical model * Similar to ML in using probability models for evolutionary change, * BI incorporates prior knowledge and calculates the probability of a tree given the data. It provides a statistical framework for estimating the uncertainty in phylogenetic inferences. * Suitable for complex datasets where incorporating prior knowledge or hypothesis testing is important. * Ideal when you need to estimate the uncertainty in your phylogenetic inferences. Pros: * Incorporates prior knowledge and uncertainty into the analysis. * Statistically rigorous, using explicit models like ML. * Provides estimates of the probability of different phylogenetic trees. Limitations: * slow * Even more computationally intensive than ML. * The choice of priors and models can significantly affect the results. * Requires careful interpretation

Answer 115

* UPGMA: where the molecular clock assumption is valid. for quick, preliminary analyses. * NJ: Ideal for large datasets where computational speed is a concern. Useful when the molecular clock assumption is questionable. * MP: dealing with well-sampled data where convergent evolution is not a significant issue. Good for analyzing morphological data, not just molecular. * ML: for all types, Ideal for analyses where accuracy is more important than computational speed. * BI: for complex datasets where incorporating prior knowledge or hypothesis testing is important. Ideal when you need to estimate the uncertainty in your phylogenetic inferences. Good for testing evolutionary hypothesis

Answer 116

* Most phylogenetic methods (UPGMA, NJ, ML, except BI) provide a single estimate of the 'true' tree * Does not measure uncertainty of these methods * Different parts of a tree (clusters) can be assessed individually for their reliability. * "Bootstrapping" is the most common technique. It involves permutation of the original data to create a large number of pseudoreplicate data sets.

Answer 117

* method in statistical analysis, especially used to measure uncertainty and confidence for branches in phylogenetics tree * uses resampling technique: repeatedly resampling the dataset with replacement. This means creating many new datasets (called bootstrap samples) by randomly selecting data points from the original dataset, allowing for the same point to be picked more than once. 1. generating many 100s-1000s of bootstrap samples by sampling with replacement 2. then generate a phylogenetics tree with each bootstrap sample. This process results in many trees, each slightly different depending on the particular sequences included in the bootstrap sample. 3. The bootstrap value for a particular branch in the original tree is calculated by determining how often that branch appears in the bootstrap trees. It's usually expressed as a percentage. For example, if a certain branch of the original tree appears in 75 out of 100 bootstrap trees, it would have a bootstrap value of 75%. 4. Interpretation: 75% is good, 95% is very robust, and any thing below 50% is rejected

Answer 118

The neutral theory holds that most variation at the molecular level does not affect fitness and, therefore, the evolutionary fate of genetic variation is best explained by stochastic processes.

Answer 119

* this is because morphology/phenotype changes is not equal to molecular changes * according to neutralist approach: MOST mutations are neutral and hence won;t be affected by mutations. Therefore, the molecular clock fits for majority of the genome, as most of the mutations are pretty constant over time Limitations * however not all parts of the genome mutate at same rate (constant rate yes, but not same, for example mitochondrial genes tend to mutate much slower) * therefore can use relaxed clock to model this

Answer 120

* Molecules can estimate the date of common ancestors for which no fossils are known (filling in gaps in the fossil record). * Molecules can estimate divergence dates when there is no obvious morphological change (particularly important for micro-organisms).

Answer 121

* use both! * seemingly contradicting to say molecular clock is constant whereas morphological data changes so rapidly in evolution * this is because of the integrated explanation of neutralist and selectionist approach * neutralist: mutations are mostly neutral and molecular changes are mostly due to random genetic drift * selectionist: genetic variations such as mutations become prevalent and fixed in the population due to selection * both approaches integrated explain why morphological data changes so rapidly in evolution, whilst molecular mutations are more constant * selectionsit explains morphological data, in stating that advantageous mutations impact the morphology very quickly, whereas deleterious ones are eliminated * neutralist explains most mutations are neutral, and those that are advantageous will spread out, but these mutations are rarer than average mutation rates

Answer 122

1. To understand why some genes/gene regions/species evolve faster than others 2. To estimate a timescale for phylogenies and evolutionary history

Answer 123

* Species genome also evolve at different rates. Depending on size of genome and C-value paradox * different parts of genes and different protein have different rates * maybe they are constant, but they are dfinetly not the SAME rate

Answer 124

* The substitution/fixation rate is the rate at which sequences in different populations diverge through time. * The mutation rate is the rate at which individuals incorporate errors during replication. **Mutation rate can affect substitution rate** * The probability of fixation determines the difference between individuals **k = Nμp = substitution rate (per generation)** * μ = mutation rate (per individual per generation) * p = probability of fixation * N = population size (2N for diploids)

Answer 125

**affecting probability of fixation (p)** 1. differences in population size 2. differences in selective pressure **affecting mutation rate per individual per generation (u)** 1. differences in generation time 2. differences in metabolic rate 3. differences in efficiency of DNA repair

Answer 126

* variation in constraints for genes: different genes have different fixation rates, some more essential genes have lower fixation rates * Sites not under selection (pseudogenes – non-fucntioning genes due to gene duplication etc have higher substitution rate ) evolve fastest

Answer 127

**For neutral mutations** * (Ns=0) p = 1/N , *** k = Nμp = μ** **For strongly advantageous mutations ** * (Ns>1) p ≈ 2s , * **k = Nμp ≈ 2Nμs** **For strongly disadvantageous mutations ** * (Ns<-1) p ≈ 0 , *** k = Nμp ≈ 0** s: The selection coefficient, which measures the effect of selection on a particular mutation. It represents the relative fitness advantage (or disadvantage) of a particular genotype compared to the standard genotype. A positive value of s indicates an advantageous mutation, Ns: The product of the effective population size and the selection coefficient, an indication of the strength of selection relative to the size of the population. It is used to assess the importance of genetic drift versus selection.

Answer 128

* Fixation of mutations depends on the product Ns (size of population and selection coefficient) * Mutations are controlled by drift when -1 < Ns < 1. * When N is small, slightly deleterious mutations (which are very common) are controlled by drift and can occasionally become fixed. * When N is large, these deleterious mutations are controlled by negative selection and never get fixed. * Hence substitution rates can increase in smaller populations. * But organisms in small populations tend to have long generation times, which may cancel out this effect.

Answer 129

* μ = mutation rate (per individual per generation) * generation time (g) = time between germ line replications, (time between generation1 reproduce and generation 2 reproduce) * substitution rates are proportional to generation times. i.e shorter generation times = faster fixation rates * generation time is a particularly important factor for selectively neutral polymorphisms (e.g. silent sites, pseudogenes) where no effect of fixation pribability (p) * example: substitution rates at silent sites for orangutan, gorilla and chimpanzee are 1.3x, 2.2x and 1.2x than that in humans, which correspond to their proportionally shorter generation times. * Not all generations are equal: variation in number of cell divisions (hence more opportunities for mutations per organismal generation). * In some species there may be more cell division events in the male germ line than the female, leading to faster Y chromosome evolution than in the X chromosome (e.g. in plants and animals).

Answer 130

* neutral: dependent on mutation rate * + selection: increases fixation probability * - selection: close to 0 fixation probability *small population: higher chance of deleterious fixation * large population: no chance of deleterious fixation due to negative selectionoutweighs genetic drift * However small population w long generation times can cancel out effect of drift to fix deleterious mutations

Answer 131

μ = mutation rate (per individual per generation) * Smaller bodied vertebrates tend to have higher substitution rates than larger bodied one * Could be due to higher basal metabolic rates (BMR) in smaller species) * Because the increased oxygen free radicals produced by aerobic respiration which can generate mutations * Higher conc of oxygen radicals could also explain why mtDNA genomes tend to evolve faster than nuclear genome * Not certain of this yet because too many factors in this, * i.e body size and BMR also correlated with generation time, could just be correlation not causation

Answer 132

μ = mutation rate (per individual per generation) * RNA viruses and retroviruses have mutation rates many times higher than those of eukaryotes because they replicate using different polymerases. * Highly transcribed genes more efficiently repaired. * Sometimes mutation is deliberate and can be adaptive * i.e bacterial hypermutator strains or hypermutation during antibody maturation

Answer 133

* generation time short = more opportunity for mutation/faster mutation rate = faster fixation * metabolic rate faster = more mutations = faster fixation * depending on how good and efficient DNA repair is.

Answer 134

Genetic distance = evolutionary rate x (2 x divergence time)

Answer 135

evolutionary rate essentially represents how many mutations per unit time. This allows us to be able to work out evolutionary history in terms of years, and give a timescale.

Answer 136

Genetic distance = evolutionary rate x (2 x divergence time) We know how to obtain genetic distances. If we know at least one divergence time (T) then we can “calibrate” the timescale of the phylogeny using that time.

Answer 137

1. Fossils 2. Biogeography 3. Co-evolution 4. Measurable evolving populations

Answer 138

* Maximum likelihood methods are used to estimate the phylogeny, with the addition that calibrated nodes are fixed to a timepoint. * Branch lengths are then in units of time, not genetic distance.

Answer 139

* Point calibration: fix a node in time (due to fossil record) and use this to calibrate * Range calibration: when unsure about certain time, and give a range of time

Answer 140

* i.e The volcanic origin of the Hawaiian islands has produced a chain of islands of increasing geological age. * Hence for example, fruit flies (Drosophila spp.) from the oldest islands form the deepest branch of the tree, and those from the younger islands are phylogenetically more derived. * For different genera, the same linear relationship is found between genetic distance and island age

Answer 141

* If coevolution between 2 species occurred, then timescale for the phylogeny of one can calibrate a phylogeny of the other.

Answer 142

* Phylogenies can be calibrated using tips (rather than internal nodes) if sequences are from evolutionarily different points in time. * **i.e: 1. Ancient DNA ** * Long periods of time (up to 750K years) between samples. * Samples are radiocarbon-dated *** i.e 2. Rapidly evolving pathogens** * RNA viruses, small DNA viruses, and some bacteria * Evolve very quickly: e.g. 10-3 - 10-5 substitutions per site per year for RNA viruses * Allow the generation of ‘distance trees’ and create a phylogenetic tree calibrated by time, using samples sequences from a species/individual at different times

Answer 143

- Substitution rate = population size * mutation rate * probability of fixation (PER GENERATION PER INDIVIDUAL)

Answer 144

- Substitution rate is different to mutation rate, substitution rate is the rate a gene is FIXED in the population/not removed

Answer 145

- Molecular clocks used to understand why some genes/gene regions/species evolve/fixed faster than others; - and form a timescale for phylogenetic trees

Answer 146

Genetic diversity, Evolutionary forces, Population structure

Answer 147

Population genetics is the study of the distributions and changes of allele frequency in a population, as the population is subject to the four main evolutionary processes: natural selection, genetic drift, mutation, and gene flow. It also takes into account factors like recombination and population structure. - seeks to understand diversity or variation, including both genotypic and phenotypic diversity - models diversity using mathematical models along with empirical data (molecular markers, phenotype, environmental)

Answer 148

* Population genetics ultimately underpin all phenomena in evolutionary biology and * essential tool in diverse areas of investigation and application * (e.g. conservation, breeding, ecology, phylogeny, evolutionary history, interactions)

Answer 149

* The study of genetic diversity in biological populations (mostly within species) and of the processes that cause genetic diversity to change * Genetic diversity is synonymous with intra-specific diversity * Inter-specific diversity refers to differences between species, mostly involves other processes and models NOT IN POP GEN

Answer 150

* the total number of genetic characteristics in the genetic makeup of a species. * It is the variability in the genes among individuals within a population, among populations within a specie. * This diversity is what enables populations to adapt to changing environments and is a fundamental component of biodiversity. * High genetic diversity usually indicates a healthy and resilient population, capable of surviving changes and challenges in their environment. * genetic diversity of a species = intra-specific diversity

Answer 151

* evolutionary forces like: natural selection, genetic drift, mutations, gene flow is used to explain some types of pop gen * explains shifts in equillibriums and some appearances of certain population structures

Answer 152

* integration of Mendelian genetics and Darwinian natural selection. * Key figures were RA Fisher, JBS Haldane, and Sewell Wright * RA Fisher: The Genetical Theory of Natural Selection,. Fisher's work helped to reconcile Mendelian genetics with Darwinian evolution, particularly through his explanation of how genetic variation is maintained in a population through balancing selections, overdominance (heterozygosity) ..etc * JBS Haldane: explored the rate at which favorable mutations can spread through a population, and providing insights into other evolutionary processes such as genetic drift * Wright: explored inbreeding and genetic drift and how genotypes are linked to reproductive success

Answer 153

* Discovery of DNA has helped to provide better understanding/quantitative understanding of pop gen * more investigations on many more species * Can sequence genomes to bring new understandings to pop gen * More species to research, research across species quickly * giving quatitative methods and models to test and verify hypothesis. * can sequence DNA and label DNA to test certain hypothesis * do more quantitative research and have more quantitative empirical data

Answer 154

- lecture focus on the effect on pop gene and variation from a single gene - **yet take in mind that many traits are controlled by multiple genes (multigenic)**

Answer 155

* Single Nucleotide Polymorphisms (SNPs): * Insertions and Deletions (Indels): * Proteins: blood groups (1900), * allozymes (electrophoretically-distinct proteins; 1966) * Structural variations (gene duplications/losses, chromosomal arrangements) * Variable Number Tandem Repeats (VNTRs):

Answer 156

* genetic markers are a subset of genetic variations * genetic markers: they are specific sequences that have been identified as useful for a particular purpose, like mapping the genome, studying population genetics, or forensic analysis. * genetic variation: diversity of gene frequencies in a population

Answer 157

1. Proteins: blood groups (1900), 2. allozymes (electrophoretically-distinct proteins; 1966) 3. VNTRs 4. SNPs (VERY USEFUL)

Answer 158

* the most common types of genetic variation among people. A SNP is a variation at a single position in a DNA sequence among individuals. they are useful because: * High Abundance: * Tracking Inheritance and Evolution * Population Structure and Diversity * Adaptation and Selection **SNPs and variation within species is important, hence also why DNA sequencing of one individual may not tell you everything about that species **

Answer 159

1. The genotype is the allelic make up on an individual 2. the genetic makeup of an individual 3. whether they are homozygous or heterozygous for certain gene(s)

Answer 160

Diploid organisms are heterozygous if they carry different alleles at a genetic locus

Answer 161

1. At population level: polymorphic, more than one allele in a population (typically > 1- 5%) a) polymorphic site - when 2 alleles are detected at a locus

Answer 162

1. There are n=6 sequences, each L=500 nucleotides long 2. Number of nucleotide sites with genetic differences (S) = 4 3. Number of distinct sequences = 5 a) Proportion of variable (segregating) sites = S/L = 4/500 = 0.008 b) Average pairwise difference (PD) = 2.0 c) Average PD per site = PD/L = 0.004

Answer 163

The average pairwise difference (PD) is the average number of nucleotide differences per comparison between two sequences. It is obtained by comparing each sequence with every other sequence and then averaging the number of differences. * Compare each sequence to every other sequence. * Count the number of differences for each comparison. * Sum all the differences. * Divide by the number of comparisons made.

Answer 164

* Measuring Genetic Diversity: Pairwise distances can be used to measure the genetic diversity within a population. High average pairwise distances indicate high genetic variation, while low pairwise distances suggest genetic homogeneity. * Phylogenetic Analysis: When constructing phylogenetic trees, pairwise distances between sequences can be used to infer evolutionary relationships. * Population Structure: For example, if certain groups within a population have smaller pairwise distances amongst themselves than with other groups, this suggests a structured population with potential subpopulations. * Identifying subpopulations and gene flow: If the genetic distance is significantly larger between populations than within them, it might indicate limited interbreeding or historical separation. * Epidemiology: tracking evolution and outbreak of disease. Observing when huge genetic diversity occured. When the pathogen evolved fastest

Answer 165

* Heterozygosity (h) is the fraction of individuals in a population that are expected to be heterozygous (normally for one gene/locus, but can be used to calculate average heterozygosity, which involves averaging across multiple genes/loci) * useful measure of genetic variation, even when there are many alleles * Individual allele frequencies is less convenient, especially when there are multiple alleles - heterozygosity presented in a fraction can be more easily compared and gives more information about the genetic diversity of a population rather than knowing specific allele frequencies for each allele * the ratio/fraction: better comparison and better picture of genetic variation in population

Answer 166

1. Average heterozygosity (H), is obtained by averaging h across many loci/many genes; it represents the proportion of loci observed to be heterozygous in an average individual.

Answer 167

* h is probability that any two alleles randomly sampled from the population are different. * It is greatest when there are many alleles, all at equal frequency * m = number of alleles for this gene * i = allele i * This formula subtracts the sum of the squared allele frequencies (which represents the probability of homozygosity) from 1 to give the probability of heterozygosity.

Answer 168

* first find each of the average heterozygosity (h) for n numbers of genes/loci (from locus 1 to locus n) * then sum them all up, and divided by the number of loci n * this gives the the average heterozygosity (fraction of heterozygotes) for multiple alleles (averaged)

Answer 169

* a mathematical model for understanding allele and genotype frequencies in a population, if the population were not affected by evolutionary forces (if the population were in a state of equilibrium), * this includes **not looking** at the effects of random genetic drift, as well as mutation, migration (gene flow), and non-random mating * HW Principle is an example of a null-model * Predicts genotype frequencies based on allele frequencies, when stable across generations in a stable population. * looks at population stability *** the equillibirum is the predicted fractions of homozygotes and heterozygotes present in population predicted by using hardy weinberg equation**

Answer 170

1. Diploid organism with sexual reproduction (random and independent chromosome transmission to offspring): ensures inheritance and sexual reproduction giving homo and heterozygous individuals occur 2. Non-overlapping generations: 3. Infinite population size (no random genetic drift) 4. Radom mating (no selection) 5. Males and females have equal allele frequencies 6. A close population (no migration/no gene flow) 7. No mutation (no evolutionary forces) 8. No natural selection effects

Answer 171

* the Hardy-Weinberg equilibrium provides a fundamental null hypothesis for population genetics, showing that sexual reproduction alone does not alter the genetic makeup of a population. * It is the interplay of genetic inheritance with evolutionary forces that shapes the genetic structure of populations over time. * Inheritance alone can maintain genetic diversity, hence biological variation is not lost through time

Answer 172

ii. The principle extends to >2 alleles and to multiple loci that segregate independently

Answer 173

It shows that in absence of evolutionary forces: 1. Genotype frequencies are in equilibrium, i.e. they remain unchanged indefinitely, as long as nothing happens to population 2. This equilibrium is reached quickly, a) after only one generation of random mating, regardless of the frequencies in the parental generation 3. If genotype frequencies are different from those predicted, then at least one evolutionary force is acting a) Population is not in equilibrium, some type of evolutionary force is present 4. When observed ratios are different to expected, important to look at the evolutionary forces

Answer 174

* while there are several evolutionary forces that shape the genetic makeup of a population, they operate through different mechanisms, yet their outcomes can influence and interact with the outcomes of natural selection. *** Molecular Level** * Mutation * Recombination * **Population Level** * Non-random mating (inbreeding) * Random Genetic Drift * Migration/gene flow *** Natural Selection or Adaptation**

Answer 175

**Linkage Disequillibrium:** * Definition: LD refers to the non-random association of alleles at two or more loci. It means that the combination of alleles on a chromosome occurs together more or less often than would be expected by chance if the loci were segregating independently. * Causes: LD can be caused by several factors physical proximity of genes on a chromosome (they are 'linked'), reduced recombination (i.e at centromeres or in X/Y chromosomes), genetic drift...etc **Recombination** * Definition: Recombination is the process by which pieces of DNA are broken and rejoined, which leads to new combinations of alleles. This occurs during meiosis, the cell division process that leads to the production of gametes (sperm and eggs). * Mechanism: During meiosis, homologous chromosomes pair up and exchange segments in a process known as crossing over. This shuffles the alleles and creates new combinations on each chromosome, which increases genetic diversity.

Answer 176

* Impact on LD: Recombination tends to break down LD over time because it creates new allele combinations. The more frequently recombination occurs between two loci, the less likely those loci are to show LD. Conversely, loci that are close together on a chromosome are less likely to be separated by recombination and are therefore more likely to exhibit LD. * LD decreases due to random re-assortment of genes (alleles) resulting from recombination * However, LD may be preserved due to selection, this is referred to as a selective sweep/hitchhiking or Background Selection (deleterious mutations + their closely linked genes are removed tgt) or Epistatic Selection

Answer 177

* Inbreeding: individuals mate with relatives more often than by chance 1. Affects all genes of an organism, increases homozygosity 2. May be adaptive: e.g. self-fertilisation in plants improves survival of isolated individuals * Positive assortative mating: occurs among individuals with similar phenotype 1. Affects a subset of genes (linked to phenotype) 2. Increase homozygosity decrease heterozygosity

Answer 178

* Inbreeding and positive assortative mating do not change allele frequencies but they increase homozygosity (vs H-W). 1. Homozygosity increases because offspring are more likely to inherit the same allele from both parents 2. This is known as Identity by Descent (IBD)

Answer 179

Inbreeding Coefficient (F): is a measure of the likelihood that an individual has received two identical alleles of a gene from an ancestor common to both its parents. AKA: the number of genes that are possibly the same 2 alleles (homozygous) F=0: This indicates random mating, with no preference or aversion to mating with relatives, which is in line with the expectations of the Hardy-Weinberg equilibrium. There's no inbreeding, so the observed heterozygosity = expected heterozygosity F=1: This represents complete inbreeding, such as self-fertilization in plants or incestuous mating in animals, where an individual's two alleles at every locus are identical by descent. This scenario predicts no heterozygotes in the population because every individual is homozygous for every gene, having inherited the exact same allele from both parents. F=0.25: This value suggests the level of inbreeding that would be expected between full siblings, meaning they share both parents. The value 0.25 comes from the fact that there is a 25% probability that any given allele from one sibling will be identical by descent to an allele in the same locus in the other sibling. This is because each parent has a 50% chance of passing on either one of their two alleles, and when you combine the probabilities from both parents, you get 0.5 * 0.5 = 0.25 Calculating Inbreeding coefficient (F): is used to measure the level of recent inbreeding 1. F = 0, random mating (H-W) 2. F = 1, complete inbreeding, no heterozygotes 3. F = 0.25, for full-siblingss (same two parents)

Answer 180

where individuals that are the result of inbreeding exhibit reduced biological fitness. Inbreeding involves the breeding of closely related individuals and often leads to an increase in homozygosity, which can bring recessive alleles, including deleterious or harmful ones, together. result in an increased expression of harmful genetic traits and a decrease in the overall genetic diversity within a population.

Answer 181

* when inbreeding and positive assortment mating causes homozygosity to appear more in the population, without changing allele frequency * homozygosity increases because there is an increased chance that the offspring inherits the same allele from both parents (more likely that parents, as they are related, have the same allele)

Answer 182

i. Reduced fitness: often results from homozygosity in recessive deleterious alleles ii. Any further inbreeding Leads to decline in populations/lowered survival rates Example: Australian Shepherds - inbreeding caused a decreased lifespan abd increase in percentage mortality as inbreeding increased over time. This eventually leads to decline in population

Answer 183

* a random process and mechanism of evolution, where changes in allele frequencies in a population over time is random. Over time, random changes in alllele frequence causes egnetic variations = genetic drft * occurs after founder's effect or bottleneck effect, (i.e after epidemic or migration event) * leads to the fixation or elimination of certain alleles by chance, especially more significant in small populations * agrees with the neutralist theory of evolution: where molecular evolutionary changes are mostly random.

Answer 184

1. founder effect: This occurs when a new population is established by a very small number of individuals from a larger population. This small group may have different allele frequencies than the original population, leading to a shift in allele frequencies in the new population. 2. Bottleneck Effect: This happens when a large population is drastically and randomly reduced in size due to an event like a natural disaster.

Answer 185

* Drift causes substantive changes in allele frequencies *Increased homozygosity is a typical outcome of drift

Answer 186

Fixation is when an allele’s frequency reaches 100% in the population (homozygosity)

Answer 187

* A founder effect is observed as a result of genetic drift and inbreeding in a subpopulation * founder's effect by genetic drift, often causes a small new population, where inbreeding occurs * this leads to increase in homozygosity * causes: high occurences of rare diseases in certain human populations; or in some wild felid populations have very low heterozygosity

Answer 188

* effective population size (Ne) is a theoretical concept to represent the genetic drift and reproduction of the actual population * Ne is used in place of census population size, because the census (actual) population size doesn't accurately reflect genetic drift's effect * It is meant to represent the population which actually contributes to genetic drift/reproduction from the census population * Ne is often smaller than N * specific to population genetics, where we are interested in reproduction in population

Answer 189

* specific to population genetics, where we are interested in reproduction in population * Because when trying to understand/calculate effects and predict genetic drift, using the actual population size (N) cannot accurately reflect the genetic drift. This is because not all individuals in all generations have an equal propensity to reproduce * This is because: 1. some of the population won't contribute to reproduction, and do not have reproductive success, hence doesn't contribute to genetic drift 2. where sex ratio is imbalanced, therefore not all individuals contribute evenly to reproduction 3. age structure: not all can contribute to reproduction 4. Fluctuating Population Size: Populations that undergo frequent changes in size (e.g., due to seasonal variations, natural disasters, etc.) often have a smaller effective population size compared to their average census size over time. * Ne is though to represent the actual population which contributes towards reproduction and hence genetic drift * The amount of (neutral) diversity in a population will depend on Ne, not N

Answer 190

* after calculating Ne (which depends on various factors and scenarios, hence uses different calculations): 1. Ne can be used to predict rates of genetic drift. By knowing Ne, we can estimate how quickly genetic variability might be lost due to drift. 2. Ne is crucial for estimating the rate of inbreeding in small populations, and how long it takes for harmful mutations to spread in population with inbreeding 3. Ne can be used in conservation biology, by determining minimum viable population size, and come up with conservation strategies for endagered species. i.e outcrossing, and captive breeding (to prevent inbreeding depression in captive breeding). 4. Ne helps in identifying past population bottlenecks and founder effects by comparing it to the actual population size. Significant discrepancies can indicate historical events that have reduced genetic diversity.

Answer 191

1. Because some individuals don’t contribute reproductively

Answer 192

* Many approaches have been developed to calculate Ne to account for the differ factors that affect population size: 1. Scenario: population size fluctures. If a population size varies through time (t), Ne is the harmonic mean of population size; it is calculated as follows: 2. Scenario: unequal sex ratio. The rarer sex will contribute more offspring per capita that the common one

Answer 193

demes = sub-populations: distinct groups within a larger population that often exhibit some degree of separation or distinctiveness, either geographically, genetically, ecologically or behaviorally. * still have gene flow (or migration) and inbreeding potential between sub-populations. Not completely isolated

Answer 194

* Gene flow, aka genetic migration, is the transfer of alleles from one population to another. It occurs when individuals from one population migrate to another and breed there. * introduces new alleles and increases genetic diversity of a sub-population, but decreases overall genetic differences between the 2 groups. * Leads to genetic homogeneity between the 2 populations, reduces overal heterozygosity (compared to HW equillibrium)

Answer 195

* island model used to illustrate migration/gene flow * Migration can increase diversity within sub-populations but decrease diversity among them * Migration can result in a reduction in overall heterozygosity (compared to H-W) * Over time, with sufficient migration between subpopulations (like an "island migration model," where multiple subpopulations or "islands" exchange individuals at equal rates), the allele frequencies in all subpopulations would be expected to converge to a common/mean frequency. This means the genetic differences between the subpopulations would decrease due to the mixing of their gene pools.

Answer 196

This equation: (2pAqA + 2pBqB)/2 finds the average heterozygosity of 2 sub-populations under H-W equillibrium, qhere pA, qA are different allele frequencies from sub-pop A, and pB, qB are diff allele freqs from sub-pop B * this average heterozygositywill always be lower in this than an equivalent mixed population. This is because the mixing of populations allows for more combinations of alleles and therefore a higher likelihood of heterozygotes. * ultimately over time, the allele frequencies will average out and converge between the 2 demes

Answer 197

1. The Fixation Index (FST) is the fraction of total genetic diversity that is due to differences among demes (sub-populations) i. FST = 1, complete divergence among demes, i.e. no migration ii. FST = 0, no divergence among demes, i.e. frequent migration, complete mix of gene pool, genetically identical

Answer 198

* We can calculate FST based on heterozygosity levels * HT: is the expected heterozygosity of the total population (considering all subpopulations as one population). * HS: is the average heterozygosity within subpopulations, and then calculating average. 1. to calculate HT= treat all sub-populations as 1 population, and calculate overall allele frequency for each allele. 2. HT-HS= gives you genetic difference of expected heterozygosity if it was all mixed into 1 population vs actual average heterozygosity across all demes

Answer 199

1. We can calculate FST based on heterozygosity levels 2. We can use FST to calculate the rate of migration (Nm) between demes

Answer 200

FST = 1 / (4Nm + 1) * vice versa: if we know FST we can then use it to resolve Nm

Answer 201

* Genetic Differentiation: tells us about difference in gene flow, and migration. Can be used to explore speciation events or ecological changes * Historical Events: if Fst/genetic difference is low, genetic drift or founders/bottleneck occured.

Answer 202

1. Clustering algorithms can identify sub-groups within a species using genetic marker data from multiple loci 2. The best known of these programs is “STRUCTURE” (Pritchard et al. 2000) 3. Use of STRUCTURE is illustrated in a study of the endangered maple, Acer miaotaiense

Answer 203

Population genetics is the study of genetic diversity in biological populations of a species, and the processes which can cause change in genetic diversity. Discovery of molecular methods have allowed us to better trach and understand population genetics in species. Population genetics helps understand the fundamentals of evolutionary changes. Population genetics aims to understand diversity of phenotypes and genotypes using mathematical models and molecular data

Answer 204

Natural selection: affects diversity by directly affecting phenotype diversity and hence causing genetic change

Answer 205

- Quantitative genetics uses numerical models and statistics to understand genetic changes on phenotypes (looking more at multigenic traits). - Genetic markers such as SNPs or other specific regions of the genome is used to measure genetic diversity in populations. - Polymorphic sites and SNPs in populations is one way to measure variation in genetic diversity in a population, and counting the proportion of variable/segregating/polymorphic sites, to measure average pairwise difference

Answer 206

If the equation doesn’t meet the expected, then other evolutionary forces are acting

Answer 207

* natural selection operates and acts on individual level, but it's effects influence and can be observed on molecular and species level * Individual Level: The process of natural selection operates on the phenotypes of individuals, not directly on their genes * molecular level: depending on the phenotype it favors, it will effect the chances the corresponding gene/genes are passed on, and whether over time it becomes fixed (or if allele freq changes) * species level: over time, effects of natural selection and phenotypic traits can cause species/population level effects like speciation

Answer 208

* Molecular level: Mutations: Recombination and genetic linkage: * Populations level: Non-random mating (inbreeding): Random genetic drift: Founder’s effect: Effective population size vs census population size Migration and Island models: Fixation Index: * Natural selection:

Answer 209

* population structure can influence the reproductive success, and hence genetic drift * therefore Ne effective population size needs to be used instead of census population size, in certain population structures such as unequal sex ratio, or fluctuating population sizes * migration and gene flow (such as the island model population structure) also effects genetic diversity -> which ultimately effects population genetics such as heterozygosity and allele frequencies * FST is used to both infer population heterzygosity, population genetic diversity, as well as migration rate (Nm) between demes

Answer 210

* organisms within a species/population differ in their ability to survive and reproduce, due to their difference in genotypes * fitness = ability to survive and reproduce * those alleles which enhance survival and reproduction ill contribute disproportionally more to the next generation's gene pool, hence changing allele frequencies over time Selection acts on the whole organism/individual

Answer 211

individual level acts on phenotypes that are associated with fitness and indirectly on genotype (allele frequencies).

Answer 212

* variation in genotype (mutations exist in population, individuals will have differing phenotypes (and corresponding different genotypes) * Heritability: phenotypes can be herited by their corresponding genotypes/alleles * differential survival rates: alleles for certain phenotypes have differentiating survival/reproductive advatanges * change in allele frequency overtime * non-directional process, which depends on envrionment, and in ongoing

Answer 213

* over time, under constant environmental selection pressure, positive selection for beneficial allele, will lead to fixation of that allele in population. * because that adv allele will increase in allele freq in gene pool until it reaches 1

Answer 214

- to understand genotypic and phenotypic variation - models diversity using mathematical models along with empirical data (molecular markers, phenotype, environmental)

Answer 215

* affects diversity by acting on phenotype and thus indirectly results genetic change * Natural (and artificial) selection specifically acts on the heritable (genetic) component of phenotypic variation * Phenotypes controlled by a single locus (gene) are useful to understand natural selection but in nature many phenotypes are under multigenic control

Answer 216

- Phenotypes controlled by a single locus (gene) are useful to understand natural selection but in nature many phenotypes are under multigenic control

Answer 217

- seeks to understand the heritable basis of phenotypic variation - It uses numerical models and statistical analyses to measure genetic effects on phenotype - ** phenotypic data alone or along with genomic data **

Answer 218

* single locus population genetics * quantitative genetics - multiple locus controlling traits

Answer 219

* positive selection * negative selection * balancing selection - favors co-existence of both allales in population

Answer 220

1. directional selection (average trait value increases or decreases) 2. disruptive selection (extreme trait values selected for) 3. stabilising selection (average trait value selected for)

Answer 221

* both negative and positive selection are directional selection

Answer 222

* both disruptive and stabilising selection are balancing selection

Answer 223

- the reproductive success of an individual with a particular genotype or phenotype. - a measure of an individual's genetic contribution to the next generation compared to other genotypes or phenotypes within the population

Answer 224

- Relative fitness is the average number of offspring produced by the individuals with a particular genotype compared with other genotypes

Answer 225

survival to reproductive age, mating success, and fecundity (the number of offspring produced).

Answer 226

- fitness of an allele is expressed as a selection coefficient (s) - represents the increase or decrease in fitness of that allele compared to others - The selection coefficient (s) is related to fitness and is a measure of the strength of natural selection against a genotype

Answer 227

- i.e Given the fitness of an allele is 1.0 (e.g. our "reference allele") - The value of s is the range: -1 < s < 1 - How do we interpret the value of s? * if s= + 0.30, means a new allele has 30% greater fitness than the previous or reference allele * s = - 0.60, means a new allele has 60% lower fitness than the previous or reference allele * s = 0, means a new allele has the same fitness than the previous or reference allele

Answer 228

- Direct fitness is the component of fitness from an individual's own offspring. - It measures the number of offspring an individual produces until they are capable of reproducing themselves.

Answer 229

Direct fitness can be calculated by counting the number of offspring an individual produces that survive to reproductive age.

Answer 230

- The component of an individual's genetic success due to the reproduction of its non-descendant relatives. - an individual can contribute genes to the next generation not only by producing its own offspring but also by aiding relatives, which share some proportion of their genes. - kin selection, altruism

Answer 231

* Indirect fitness is typically calculated by measuring the reproductive success of the individual's relatives, multiplied by the degree of relatedness to those relatives. * For example, if an individual helps a sibling (with whom they share, on average, 50% of their genes) to produce extra offspring, the indirect fitness gain would be those additional offspring multiplied by 0.5.

Answer 232

* Inclusive fitness combines direct and indirect fitness. It represents an individual's total genetic contribution to the next generation, including genes passed on directly as well as genes passed on by relatives due in part to the individual's assistance or influence.

Answer 233

um of direct fitness and weighted indirect fitness contributions. The weights are the coefficients of relatedness between the individual and the relatives they support.

Answer 234

because then we can understand hamilton's rule of kin selection when C

Answer 235

* Changes in allele in frequency (∆q) can occur more rapidly in haploids (n) than diploids (2n) * This is because the relationship between genotype and phenotype is simpler in haploids * Diploids can be heterozygote and ‘hide’ some allele’s traits

Answer 236

* ∆q = spq * p, q are the frequencies of the alleles P and Q, respectively - The Q allele has a fitness of 1+s - ∆q is the change in q from one generation to the next

Answer 237

* ∆q = spq * q increases when s is positive (fitness is higher than average), and q decreases when s is negative (fitness is below average for this allele) * Allele frequency change is slower when either P or Q are extreme, and fastest when p = q = 0.5

Answer 238

- When p and q are both at 0.5, it means both alleles are equally frequent in the population. - Under such conditions, the product pq will be at its maximum (since 0.5 x 0.5 = 0.25), leading to the fastest change in allele frequency as per the equation ∆q = spq. - Conversely, when either p or q is near 0 or 1 (meaning one allele is very rare or very common), the product pq will be closer to 0, resulting in a slower change in allele frequency. (p+q add to 1, so if p is 0.7 and q is 0.3 - more extreme values, then 07*0.3 is less than 0.25, only when p q are at 0.5, it is largest 0.25)

Answer 239

sigmoidal curve,

Answer 240

rapid selection and fixation influenza virus

Answer 241

- In diploids, fitness is influenced by the degree of dominance (h) of an allele, as follows: - PP = 1 ; - PQ = 1 + hs ; - QQ = 1 + s - H ranges from 0 to 1

Answer 242

* h = degree of dominance (0-1), 0 is completely recessive, 1 is completely dominant * Alleles P and Q exist * for PP = 1 (baseline fitness score for the PP genotype. It's saying that individuals with the PP genotype have a fitness that is not affected by the selection against the Q allele (since they do not carry it). * for PQ = 1 + hs: heterzoygous. If h = 0, Q is completelt recessive, and fitness for PQ = PP, and if h = 0, then Q is completely dominant, and fitness of PQ = QQ. If h is 0-1, then incomplete dominance * for QQ = 1+s. The baseline fitness plus whatever the selection is for this genotype. h is not considered as it is homozygous

Answer 243

Using the equations: * PP = 1 * PQ = 1+hs * QQ = 1+s

Answer 244

level of dominance

Answer 245

The alleles are co-dominant

Answer 246

* selection and dominance in diploid population * p, q are allele frequencies for 2 alleles * ∆q = spq [ph + q(1-h)] the relative fitness effect of the q allele in heterozygotes compared to homozygotes. * ∆q is change in allele frequency q over 1 generation * and [ph + q(1-h)] is the relative fitness effect of the q allele in heterozygotes compared to homozygotes. If h=0.5, there is no difference in the relative fitness effect between the two types of homozygotes. If h>0.5, the q allele is more dominant, and if h<0.5, the q allele is more recessive. * pq = proportion/frequency of heterozygosity PQ in population * s times the whole equation: tells you whether q frequence increase (s is negative) or decrease (s is positive) in the next equation

Answer 247

∆q = spq [ph + q(1-h)] * change in q allele frequency in diploid population from one generationto the next * How much the frequency of the q allele is expected to decrease (if s is positive) or increase (if s is negative) in the next generation, taking into account the current allele frequencies and the selection pressure against the q allele. * models the impact of selection on allele frequencies, giving us an estimate of the evolutionary dynamics within a population.

Answer 248

the rate of allele change

Answer 249

* If the selected allele is dominant, change is initially rapid (increase), and faster in the middle but very slow as it nears fixation * It spreads initially very quickly because initially heterozygous spreads quickly * but hard to fixate as the unbeneficial or recessive alleles are hard to completely remove due to the ‘hidden’ nature of heterozygotes

Answer 250

* change is very slow initially but accelerates near fixation * very slow initially as chances of heterozygoues getting tigether to produce a selectively advatange recessive homozygous is rare and low in chances, so takes a long time * but once the population has a lot of recessivce homozygotes, the dominant not selected allele can't hide and is removed quickly

Answer 251

- Change is initially rapid and reaches fixation very rapidly (green line) - This is because less-fit alleles are more effectively selected against (they cannot hide)

Answer 252

* when heterozygous advantage occurs * where heterozygous pq is in excess of HW equillibrium * Both alleles will stably coexist with frequency that is proportional to the relative fitnesses of the two homozygotes

Answer 253

- Sickle cell anaemia: homozygotes suffer from anaemia but heterozygotes have protection against malaria -

Answer 254

* Frequency dependent selection: the larger the frequency of a genotype, the lower its fitness, and vice versa - Example: Self-incompatibility genes in plants control the germination of pollen on the female stigma and discriminate between self and nonself. Successful pollination occurs only when pollen and stigma are of opposite types. In such cases, a population would theoretically maintain multiple self-incompatibility alleles. - Example 2: in warning coloration of plants to avoid bird predation. * Fluctuation selection: allele fitness depends on an aspect of the environment that is rapidly and constantly changing

Answer 255

* means not a simple on/off, but more on a scale. Varies in degrees/levels * often polygenic, and controlled by multiple loci * often represented in a normal distrivution (whereas single loci is skewed distribution) * quatitative traits: i.e hair color, height, eye color, skin color (varies and controlled by a lot of factors)

Answer 256

* specific regions of the genome that correlate with the variation in a quantitative trait. * Mapping these loci can be complex because each locus may have a very small effect on the trait. * requires specific statistical approaches

Answer 257

* Crop and animal breeding: picking advantageous alleles * Conservation genetics: ensuring conserved and variation in genetics to avoid certain diseases * Ecology: conservation of genetic variations * Forensic sciences: paternity tests * Disease epidemiology: mapping spread of disease in population * Anthropology and archaeology * Medical genetics

Answer 258

* after constructing tree, can be used to interpret macroevolutionary models FOR SPECIES LEVEL: (such as co-evolution, adaptive radiation..etc) * It can also be used to interpret POPULATION LEVEL PROCESSES: such as birth, death...etc * and population level processes is interpreted by coalescent theory

Answer 259

- a model of how alleles sampled from a population may have originated from a common ancestor. - In the simplest case, coalescent theory assumes no recombination, no natural selection, and no gene flow or population structure, meaning that each variant is equally likely to have been passed from one generation to the next. (variations exist which include more factors like gene flow) - The model looks backward in time, merging alleles into a single ancestral copy according to a random process in coalescence events. - Coalesce = to come together as one - Consider a single gene locus sampled from two haploid individuals in a population. The ancestry of this sample is traced backwards in time to the point where these two lineages coalesce in their most recent common ancestor (MRCA). Coalescent theory seeks to estimate the expectation of this time period and its variance.

Answer 260

* population-level processes: structures/changes to a population * coalescent theory can be used to understand certain population-level processes such as * disease gene mapping: how a certain disease gene like cystic fibrosis has been inherited through the family, * genomic distribution of heterozygoisty through tracking SNPs * population bottlenecks * population growth * source-sink dynamics * introgression (hybridisation via repeated back-crossing)

Answer 261

* disease gene mapping: how a certain disease gene like cystic fibrosis has been inherited through the family, * genomic distribution of heterozygoisty through tracking SNPs * population bottlenecks * population growth * source-sink dynamics * introgression (hybridisation via repeated back-crossing)

Answer 262

* extension of population genetics and normally assumes neutrality, and * selects sequences from more neutrally evolving portions of genomes for analysis

Answer 263

1. differences in genetic diversity 2. compare silent and replacement changes within a gene 3. McDonald Kreitmen test: 4. look for parallel/convergent evolutionary changes

Answer 264

dN/dS = 1: neutral evolution dN/ds < 1 = purifying or natural selection, nonsynonymour occuring at lower rate = conservation of proteins eq and function

Answer 265

1. hard sweep: genetic hitch hiking: neutral mutation close to selected gene dragged across 2. multiple beneficial alleles sweeped through, bringing heir linked genes 3. single mutation sweeps through due to shift in selection. soft single sweep is due to this neutral allele existed prev, but bcuz of shift in selection, it became beneficial

Answer 266

* reduction in genetic diversity around dhfr locus in malaria * genetic diversity increases as you move away from locus

Answer 267

* dependent on selection coefficient: the relative fitness between 2 genotypes or alleles * s>0 : positive selection, hence fixation of a gene * s~0: can lead to genetic drift. * hence can be fixation or elimination * s<0: negative selection leads to elimination􏰣

Answer 268

Ns is a composite parameter of population selection strength * For neutral mutations (Ns=0) , P (probability of fixation) = 1/N , k = Nup = u * For strongly advantageous mutations (Ns>1), p ~2s , k = Nup~2Nus * For strongly disadvantageous mutations (Ns<-1), p ~0 , k = Nup ~0 * Stronger the positive selection, the faster rate of substitution  Negative selection = no fixation rate

Answer 269

* If all replacement mutations are neutral, then dN/dS = 1 * If all replacement mutations are deleterious, then dN/dS = 0 * dN/dS > 1 only if at least some replacement fixations are beneficial * When applied to whole genes, dN/dS is usually much less than 1. * because only a few codons are positively selected. * Most codons are selectively constrained (i.e. strong negative selection) to conserve the functions of important codons and therefore have a dN/dS close to zero.

Answer 270

1. high dN/dS in codons that form active sites of genes 2. due to host pathogen arms race 3. high positive selection for non synonymous mutations which allow diversification to detect pathogen antigens

Answer 271

* Overlapping genes and alternate reading frames. * Very common viruses with small genomes (e.g. HIV) * Regulatory sequence elements * Promotors, enhancers, splicing elements, miRNAs * Affect stability of RNA / mRNA / DNA structure * Codons for the same amino acid differ in fitness * May result from (i) different tRNA abundances, (ii) different translational efficiency / accuracy. Changes to processivity of translation may also affect protein folding. * Gives rise to codon bias and codon pair bias. * Biases in the process of mutation may also cause some codons to be used more often than others.

Answer 272

* MK test is a stats test used to detect natural selection in molecular sequences * The MK test compares the number of non-synonymous mutations to synonymous (silent) mutations within a species (polymorphic sites) and between species (fixed sites). * If results show no selection, then the sites differences are purely due to genetic drift and neutral evolution, which would mean that the ratio of silent:replacement fixed sites are equal to the ration of silent:replacement polymorphic sites

Answer 273

* small infectious particles/agents replicate inside living cells * high mutation rates * measurable in evolving populations * evolution occurs between hosts and within hosts

Answer 274

* Single genome * New diversity generated by mutation and recombination * Gradual evolution

Answer 275

* Comprises 8 genome segments, * each segment encoding 1 or more genes * New diversity generated by mutation and reassortment * Reassortment between segments can also occur * Contrast w HIV: * No recombination in Influenza, whereas HIV has lots of recombination of segments

Answer 276

* reverse transcriptase = very error prone * Retroviruses: like HIV are group VI viruses; Use reverse trascriptase to replicate * Error prone and high mutation rate; Generally faster evolution and adaptation * Hepatitis B Virus (VII), Use reverse transcriptase to replicate; Error prone; High mutation rate * Coronavirus family (type IV); Uses RNA-Deoendent RNA polymerase (RdRp) to replicate; Error prone * Influenza (Type V); Uses RdRp; Also error prone

Answer 277

* within host scale * and between host scale * often evolution for within host is detrimental for trasnmission/between host scale, hence virus must choose one scale to evolve at * Within host : * Multiple sequence from the same individual at different time * Virus evolves during its infection period when it is in host * Between host/population level * This approach looks at the evolution of the virus across different individuals. * Consensus sequences are derived from different individuals, possibly at different times or in different locations, to understand how the virus is evolving at the population level. * This can reveal patterns of transmission, how the virus adapts to different populations, and the emergence and spread of new variants

Answer 278

* SARS-CoV-2 virus responsible for COVID-19, between-host genomics has been crucial for tracking the spread of the virus and identifying the emergence of new variants that may be more transmissible or evade vaccine-induced immunity.

Answer 279

1) acute infection: * influenza/sars * RNA viruses * lselection for transmission * can cause chronic infections in immunocomprimised patients 2) latent persistent infections * herpes simplex cirus * DNA virus - lower mutation rate * short bust of high viral load, go into dormant before next burst * selection for transmission is important 3) chronic persistent * HIV-1 * high mutation * ongoing rapud evolution * within host selection more important

Answer 280

* Data from 11 HIV-1 infected individuals serially sampled for about 8 years and using whole-genome sequencing * Selected mutations typically involve evasion from host immunity * Mutations that are selected for in some individuals are selection against in others * Divergence, showing HIV-1 adapted to specific host environment

Answer 281

* Adapt and revert can explain why we see faster rates of evolution within individuals * Virus have within host adaptation, and then be transmissed to another individual where it adapts and reverts to its previous/original states if the conditions change again * a virus might 'adapt' by mutating in a way that benefits its survival or transmission within a specific host, but then those mutations may 'revert' to a previous state if that adaptation is no longer advantageous in a new environment or host. This can be a way for viruses to maintain fitness across diverse environments and hosts, and is part of the reason why viral evolution can be so rapid and difficult to predict or control *

Answer 282

* HIV viruses * reversion of CTLs to escape after transmission * Mother infected with HIV is HLA B577/5801 positive, which means it has HLA + type that affects her immune response. The virus in mother has evolved to have CTL escape mutation T242N adapted to evade mother’s immune response, giving virus fitness advantage * Child Viral strain: after HIV transmission to child, who is HLA B57/5801 negative. The T242N mutation of HIV now is not adapted to child immune response, and has a fitness disadvantage, * Hence virus reverts back to wild-type without the mutation

Answer 283

* slow rate of evolution between host * due to constant toggling and reverting which produces diff selection pressure

Answer 284

* i.e in COVID-19 * long branches leading to variants of concerns * long branches are due to within host evolution during a chronic infection * causing within host and between host evolutions

Answer 285

* Monkeypox is a dsDNA virus (related to smallpox) * Natural low evol rate: 9x10-6 per sub/site/year (1-2 nucleotide changes per year) * But in human populations the substitution rate has been much higher * Like a consequence of the action of APOBEC3 in humans: * APOBEC3 protein in humans can induce hypermutation in viral DNA: which can lead to a higher mutation rate in viruses that infect humans. * Hence a higher substitution rate * This may drive the monkeypox to adapt faster to infect human population

Answer 286

* the lack of correlation between organism complexity and genome size

Answer 287

1. It has essential global regulatory functions for gene expression. 2. It is "junk" DNA with no use, carried passively by chromosome simply because it is linked/hitchhiked to functional genes 3. It serves a structural role in the genome, related to chromosome structure or nucleoskeletal function (i.e related to cell volume) but not to carry information. 4. It is "selfish" DNA that exists only to replicate itself, offering no benefit to the host.

Answer 288

1: Skeletal function of Genome size and Cell Volume: requiring more DNA for larger cells. ensure a constant nucleus-to-cell volume ratio for balanced RNA and protein synthesis backed by evidence in algae: DNA content correlated in nuclear volume

Answer 289

effective population sizes are too small for natural selection to effectively remove non-coding DNA from eukaryotic genomes - NeS<1 so genetic drift dominates evolutionary dynamics - Hence see fixation of slightly deleterious/non-functional genes - In contrast, large effective population sizes in bacteria could allow removal of non-coding DNA due to Natural Selection

Answer 290

* non-coding DNA little in bacteria, becuz it takes way to long to replicate from single origin * too long of a generation time and would be incredibly costly

Answer 291

1. satelite DNA 2. minisatelites 3. TE and endogenous retroviruses 4. spacer DNA

Answer 292

* both are repetitive * satelite more repetitive * satelites located in heterochromatin * mini and microsatelites have G-rich core

Answer 293

* Both have extremely high mutation rates * mostly caused by point mutation, unequal crossing over and DNA slippage (DNA mispair during replication and recombination)

Answer 294

* Selfish DNA sequences which are able to increase their copy number by jumping (transpose) around the genome and making additional copies of themselves as they do so. * ~50% of genomes of some eukaryotes including humans (42.5%) * Major component of non-coding DNA in HUMANS

Answer 295

1. class I elements (retroelements): further split into LTR retrotransposons and non-LTR retrotransposons 2. Class II elements (DNA elements) 3. MITES

Answer 296

a) Have long terminal repeats (hundreds of bp repeats) b) Include retrotransposons, endogenous retroviruses c) Move within genome by transcribing their RNA into cDNA then inserted within genome d) The LTR are regulatory sequences for retrotransposons, play critical role in reverse transcription i. Promotor, terminator, and helps stabilize retrotransposons e) Present in human genome but most are inactive, apart from the HERVs which are still somewhat active

Answer 297

a) More active in human genome causing mutations and genetic variation b) No LTR i. But transcribed RNA includes reverse transcriptase which has ‘target primed reverse transcriptase (TPRT), which allows the target DNA to act as a primer for reverse transcriptase to transcribe RNA to DNA

Answer 298

1. Ac-like elements, activator of TE 2. contain transposase 3. Transposase (helps movement within genome) 4. Terminal inverted repeats (TIRs), transposase will recognize this class of TE as they are flanked by TIRs 5. Cut and paste mechanism: transposase cuts the element from one location in the genome and pastes/integrates it into another location. 6. Non-replicative: does not involve replication of the element, meaning that it is excised from the original location when it is inserted into a new location. 7. Different from class 1, where it is replicated and integrated

Answer 299

1. Don’t make any proteins, rely on other transposon’s protein to copty itself 2. Also has TIR flanking egions 3. Non-autonomous: don’t encode for enzymes necessary for movement 4. Rely on transposases encoded by other autonomous elements 5. High numbers of copy in genome 6. Their insertion in target site associated with short direct repeats

Answer 300

* regulate gene expression 1. MITEs can affect gene expression of nearby genes and can alter chromatin structure 2. Genomic diversity by inserting and integrating into various sites 3. Evolution: contribute to genomic rearrangement and speciation process 4. Mutation: integration of TE can disrupt gene fucntion and lead to mutations

Answer 301

* LINES: which are very common in eukaryotes; insertion of retroelements into genes can cause deleterious mutations. For example, insertion of L1 into the gene for factor VIII can cause haemophilia, codes reverse transcriptase * SINES: 1. although these do not encode their own reverse transcriptase 2. parasitize inverse transcriptase from LINEs

Answer 302

* TEs accumulate rapidly in genomes * up to 100 copies in 1 generation * maize genome increased 50% in 6 million years due to insertion of 23 retrotransposons * may be difficult to remove, but they accumulate fast

Answer 303

1. Wild flied carry P elements while lab strains didn’t 2. D. melanogaster the insertion of P elements can lead to hybrid dysgenesis (an increased infertility due to chromosome breakage) 3. Hybrid dysgenesis only occurs in the offspring of crosses between females from laboratory strains and males from wild strains. 4. transposable elements like P elements might have create reproductive isolation * Causing speciation?? * Possibility of TE in causing or contributing to speciation * P element is a 3kb clas II element

Answer 304

* this type of life cycle - endogenous life style * Retroviral infection of germline * Fixation * Amplification * Inactivation through mutations * Loss through recombinational deletion * Decay into junk * Co-option (changes in function, or new function arises)

Answer 305

* ERV were acquired through endogenous life style * all 3 classes of ERVs active in mice, but onlu Class 2 is still somewhat active in humans * HERV-K(HLM2) still active in humans and can still express envelope preoteins, and can cause cancer * rare retro transposition of HERVs can lead to mutagenesis,and genetic disorders but this is rare * HERV-K(HLM2) encodes Rec protein, when injected into immunocomprimised mice, it induced tumour formation

Answer 306

1. co-option: 2. salivary amylase gene, with LTRs acting as promoters for regulation of this gene

Answer 307

1. ERVs and TEs can lead to chromosomal rearrangement through homologous recombination between distant loci - In the HERV-K(HML2) family, 16% of elements may have been involved in large scale rearrangements of the human genome. 2. Most large scale rearrangements will be highly deleterious. - HOWEVER, The ectopic exchange hypothesis predicts that TEs will be preferentially found in regions of low recombination. - mammals undergo lower levels of ectopic exchange maybe due to high levels of retroelement activity in early evolution

Answer 308

* ectopic exchange - recombinations between TEs adn other positions on genome. Ectopic exchanges happens between sequences at diff locations causing chromosomal rearrangement * Selection against TEs that cause ectopic exchange is the major force limiting TE copy numbers in genomes. because TE ectopic exchange is deleterious * Prediction: TEs likely to be found in regions that undergo lower levels of meiotic recombination because these areas have higher risk of ectopic exchange and would have been selected against * significant test results in humans and flies which outcross * less significant in HERVs for unknown reasons and self-fertilising

Answer 309

- They include regulatory elements: 1. Promoters, enhancers, silencers..etc 2. Non-protein-coding genes: rRNA, tRNA, microRNA 3. chromosomal structural elements: centromeres and telomeres, other elements which help chromosome folding and nuclear organization

Answer 310

* measure its evolution rate or fixation rate across species, if it is very slowly evolving = likely to be highly conserved

Answer 311

* human accelerated regions * Identified that HAR1: most rapidly diverging region in HARs is part of a gene that produces RNA (not protein) 1. This RNA gene is involved in the development of the human cerebral cortex (part of brain for complex cognitive functions) 2. Evolution of HAR1 may have contributed to the unique aspects of human brain development and function 3. HAR 1 is expresent during development of human neocortex (7-19 weeks of gestation) - Maybe HAR1 is responsible for the unique cognitive abilities of humans

Answer 312

How It Works: 1. DNA Preparation: DNA is first cloned into vectors and amplified. 2. Primer Annealing: A primer is annealed to a single-stranded DNA template. 3. Chain Termination: Incorporation of chain-terminating dideoxynucleotides (ddNTPs) during the DNA synthesis process. Each ddNTP is labeled with a different fluorescent dye. 4. Electrophoresis and Detection: The resulting DNA fragments are separated by size using capillary electrophoresis, and the ddNTPs are detected based on their fluorescent labels. * Key Features: 1. Produces long read lengths (up to 900 bases). 2. High accuracy but relatively low throughput and higher cost per base compared to newer methods.

Answer 313

How It Works: 1. Library Preparation: DNA is randomly fragmented, and adapters are ligated to both ends of the fragments. 2. Cluster Generation (Illumina-specific): DNA fragments are attached to a solid surface and amplified locally to form dense clusters of identical DNA molecules. 3. Sequencing by Synthesis (Illumina): Incorporates fluorescently labeled nucleotides one at a time, imaging each incorporation event. * Key Features: 1. Provides shorter read lengths than Sanger sequencing (typically 100-300 bases) but much higher throughput. 2. Lower cost per base and capable of sequencing millions of fragments simultaneously. 3. Ideal for whole-genome sequencing, resequencing, and various genomic applications.

Answer 314

* allows for massive parallel sequencing of DNA and RNA 1. Library Preparation: Similar to other second-generation methods, NGS involves preparing a library of DNA fragments with adapters added to each end. The library can be tailored for different applications, such as whole-genome sequencing, exome sequencing, or targeted sequencing. 2. Cluster Generation: On platforms like Illumina, once the library is prepared, DNA fragments are attached to a flow cell where each fragment is clonally amplified. 3. Sequencing: * Sequencing by Synthesis (e.g., Illumina): This involves synthesizing the complementary DNA strand and capturing images after each nucleotide addition. Each of the four nucleotides is tagged with a different fluorescent marker. * Nanopore Sequencing (e.g., Oxford Nanopore): Involves passing a DNA strand through a nanopore and measuring changes in electrical conductivity caused by different bases. 4. Data Analysis: The raw data generated by these technologies are then processed using bioinformatics tools to align reads and identify genetic variants.

Answer 315

* whole genome duplication events * arises from polyploidization events followed by chromosome reshaping * it can either lead to WGD being fixed if chromosome reshaping is involved

Answer 316

* WGD doubles genome size and gene number, initially * Acting over 100s of MYA * Has profound effects on the evolution genome architecture * Underpins innovations and adaptation in flowering plants (Angiosperms) * Not sufficient to account for very large genome sizes (monocots, gymnosperm

Answer 317

* Plant LTR-retrotransposons are classified into two super-families, * Ty1/copia and Ty3/gypsy. * Enormous number of families with highly diverse DNA sequences; * these are usually specific to a single or a group of closely related species

Answer 318

* LTR-RT comprises 30-70% of monocot genomes * Maize: 65% of the genome is LTR-RT sequence, representing 1.5 Gigabases * LTR-RT tend to be highly nested; this makes genome sequence analysis very challenging * Whilst most LTR-RT are degenerate and inactive, stress tends to active the movement of intact copies

Answer 319

* LRT are most abundant TEs in nearly all plants * their abundance is generally what causes large genomes

Answer 320

Two main types of interest 1. Autopolyploidy: Multiple chromosome sets derived from a single taxon. Results from No chromosome disjunction during meiosis producing abnormal gametes OR Spontaneous, somatic genome doubling, which has been observed in plants (e.g. fruit trees). 2. Allopolyploidy. Multiple chromosomes derived from two or more diverged taxa.

Answer 321

* Chromosome reshaping following WGD accounts for much of the diversity in the makeup and structure of plant genomes * The fate of duplicated genes is influenced by major evolutionary forces including adaptation

Answer 322

* Can cause rapid and short term phenotypic change. Multiple (e.g. gene expression) and complex molecular effects result from combining different genomes * Polyploids are common across Angiosperms but infrequent in Gymnosperms * Phenotypic effects can be large, and several of the “beneficial” changes have been captured in plant domestication and the development of plant varieties used in agriculture

MT Host + Genomics Flashcards

(352 cards)