Lecture 6 Evolutionary genetics

Question 1

What has evolution to do with genetics?

Answer 1

*DNA is very precious. It is long-lasting, in Eukaryotes is housed in the nucleus and stays there for the whole process.

*The genome is very large (it contains an entire organism’s “instruction manual”). A cell can find the relevant section and make a copy (TRANSCRIBE) from RNA.

*RNA moves out of the nucleus, into the cytoplasm to be TRANSLATED into protein.

Question 2

what is the central dogma of biology?

Answer 2

DNA replication->transcription->translation

Question 3

what are genes and alleles?

Answer 3

Gene:a segment of DNA involved in producing a polypeptide chain

Can include regions that don’t code for amino acids (UTRs, promoter, introns…)

A unit of heredity

Mendel’s “heritable factors”

Allele: one of a series of alternative forms of a gene that occupy the same locus on a particular chromosome and that control the same character

Mendel’s “alternative versions”

e.g. the pea gene controlling flower colour has two alleles: Pand p The human gene controlling ABO blood type has three alleles: IA, IB and i

Question 4

Where did the study of genetics start?

Answer 4

A long time ago!
Heredity has been discussed since antiquity –Ancient Indians & Ancient Greeks had theories about how traits are passed from parents to offspring

Johann Gregor Mendel (1822-84): the modern “father” of genetics

What did he do?
Studied inheritance in peas in a quantitative way:

Crossed peas with distinctive characters, recorded and analysed results mathematically.

Hypotheses: do the traits blend(like paint) or are they discrete heritable units?

Question 5

what were Mendel’s experiments?

Answer 5

Pea plants with distinct characters, e.g. flower colour –always either white or purple, no intermediates

Remove stamen (pollen-producing) while immature to prevent self-fertilisation

Cross fertilise: pollen from white flowers to carpel from purple flowers and vice-versa

Results:
First filial offspring (F1) –all purple

Second filial offspring (F2) –705 purple, 224 white

Question 6

Mendel’s experiments: conclusions

Answer 6

Conclusions

Reject blending model of inheritance –all F1 flowers are as purple as parents

White trait isn’t lost –it appears again in the F2 generation

White trait is hidden by the purple trait: white trait is recessive, purple trait is dominant.

Mendel used the term “heritable factor” –today we call these genes

The ratio in the F2generation is always approx. 3 : 1 dominant : recessive

Based on this Mendel proposed a model culminating in the Law of Segregation

Question 7

Mendel’s first law: Segregation

Answer 7

1. Alternative versions of heritable factors account for variations in inherited characters
2. For each character each organism inherits two copies of each heritable factor, one from each parent
3. If the two versions differ then one, the dominant version, determines the organism’s appearance while the other (recessive) has no noticeable effect on the organism’s appearance
4. The two copies of a heritable character separate from one another during the formation of the gametes, ending up in different gametes

Question 8

Mendel’s second law: Independent Assortment

Answer 8

Mendel’s second law, also known as the Law of Independent Assortment, describes how different genes segregate independently of each other during the formation of gametes (sex cells). This principle applies when genes for different traits are located on different chromosomes or are far apart from each other on the same chromosome. Mendel’s experiments with pea plants helped elucidate this principle.

Here’s an explanation of Mendel’s Law of Independent Assortment:

Two Genes on Different Chromosomes: When an individual inherits two genes for different traits located on different chromosomes, the alleles for each trait segregate independently during gamete formation. This means that the assortment of one pair of alleles into gametes is not influenced by the assortment of another pair of alleles.

Random Alignment during Meiosis I: During meiosis, homologous chromosomes line up randomly at the metaphase plate during metaphase I. This random alignment ensures that each gamete receives a random combination of maternal and paternal chromosomes, leading to genetic diversity in the offspring.

Genetic Variation: Independent assortment results in the production of gametes with different combinations of alleles for different genes. This genetic variation contributes to the diversity of offspring produced in sexually reproducing organisms.

Exceptions to Independent Assortment: The Law of Independent Assortment applies when genes are located on different chromosomes or are far apart from each other on the same chromosome. However, genes located close together on the same chromosome may not assort independently due to genetic linkage, which is the tendency of alleles to be inherited together.

Question 9

how did Understanding Mendelian genetics mean now we know about DNA?

Answer 9

As predicted by Mendel’s experimentsPea plants are diploid: 2 copies of each chromosome
-So are humans… and many other species

Therefore:
-2 copies of each heritable factor potentially with alternative versions
-2 copies of eachgene potentially with different alleles

During meiosis, haploid gametes are produced & the alleles segregate

Question 10

define locus, homozygous and heterozygous

Answer 10

Definitions:
Locus (plural loci) –a specific position on a chromosome where a gene is located

Homozygous –having two identical alleles for a particular gene

Heterozygous –having two different alleles for a particular gene

Question 11

what is Genetic Variation

Answer 11

Genetic variation among individuals is caused by differences in genes or other DNA segments

Phenotype is the product of inherited genotype and environmental influences

Natural selection can only act on variation with a genetic component

Question 12

Where does genetic variability come from?

Answer 12

Errors may occur during the replication of DNA

If this occurs in the gametes (eggs and sperm) it manifests in the offspring

If it affects a protein (level or sequence) it may impact on the organism

Question 13

what is a silent mutation?

Answer 13

Silent mutation: no change in amino acid sequence e.g. GAG →GAA both encode glutamate

-Lots of DNA is “junk” –doesn’t encode anything

Question 14

what is conservative mutation?

Answer 14

Conservative mutation: one amino acid is changed for a similar amino acid

-e.g. GAG →GAC means aspartate replaces glutamate

-Some amino acids changes might not affect protein function

Question 15

what is Non-conservative (mis-sense) mutation?

Answer 15

one amino acid is changed for a very different amino acid

e.g. GAG →CAG means lysine replaces glutamate

Some amino acids might have a key function

Question 16

what is a nonsense mutation

Answer 16

Nonsense mutation: stop codon (protein is truncated)Null allele: no functional protein is produced at al

Question 17

Why might alleles be dominant or recessive?

Answer 17

Imagine an enzyme, Bluaseis encoded by the gene BLU and is responsible for producing the purple pigment in flowers.

It catalyses this reaction: White pigment →Purple pigmentBLUis present as two alleles: BLU, with an alanine in position 12, and blu where the alanine is replaced by aspartate.

BLU encodes a functioning copy of the enzyme, blu encodes a version that doesn’t fold properly so isn’t functional.

Any plant with a BLUallele will still be able to do the white →purple reaction, because there is a functional copy of the enzyme present.

It doesn’t matter if a non-functional copy is also present, so BLU/BLU and BLU/blu plants will have purple flowers.

However, blu/bluplants have white flowers because no functional copy of Bluaseis present.

This means BLUis dominantbut bluis recessive

Question 18

4. Genotypes and phenotypes

Answer 18

Phenotype: The observable traitsor characteristics of an organism, e.g. hair colour, weight, presence/absence of a disease

Note phenotypic traits might not necessarily be entirely genetic

Genotype: The genetic constitution of an organism (i.e. the specific allele makeup of the individual) usually when referring to a specific character under consideration

e.g. a person whose phenotypeis blood group A can have the genotype IAIA or IAi
A pea plant with phenotype purple flowers can have genotype PP or Pp

Question 19

what is incomplete dominance?

Answer 19

Incomplete dominance
e.g. red vs white flowers in snapdragons

CWallele null (the protein encoded makes no pigment)

CR allele does not make enough to compensate therefore

CRCW flowers are pink

Question 20

what is codominance?

Answer 20

Both alleles contribute separately to phenotype e.g. ABO blood group: alleles IA & IB codominant

Question 21

what is complete dominance?

Answer 21

e.g. purple vs white flower colour in pea

Question 22

Do genetic traits always assort independently?

Answer 22

A chromosome is one long string of DNA so genes on the same chromosome are, in theory, linked together

However recombination happens during meiosis

The further apart two genes are the more likely it is that recombination will occur in between them

This can be used to map genetic loci

Question 23

what is Pleiotropy and epistasis?

Answer 23

Pleiotropy: one gene affects several phenotypic characters
e.g. people with red hair are usually fair-skinned

Epistasis: expression of a gene at one locus impacts on a gene at a second locus
e.g. coat colour in Labradors: black, chocolate or golden

Two gene loci involved:
-Locus 1:affects pigment synthesis
allele B(black) dominant to b(brown)

-Locus 2: affects pigment deposition to hair
allele E(deposition) dominant to e(no deposition)

E/e gene is epistatic to B/bgene

Question 24

What causes this variation?

Answer 24

Many characters do not show the distinctive forms but vary along a continuum

What causes this variation?

1.Not one or two but many different alleles (e.g. enzymes with subtly different activity)

2.Not one or two but many different genes might contribute (MC1R, KITLGM, ASIP, SLC14a5, TYR… are all genes involved in determining skin colour).

3.Could be non-genetic input.

Question 25

what are Multifactorial traits –the impact of environment on phenotype

Answer 25

Hydrangeas can be pink to violet in colour. Genetically identical, but colour also depends on soil acidity and aluminium content. The norm of reaction The phenotypic range of a particular genotype varies. No range: ABO blood type Broad range: Hydrangea colour In between: Height, weight, skin colour.

Question 26

Multifactorial traits what can affect the expression of characteristics?

Answer 26

both genes and the environment

Question 27

what characteristics are 50/50 genetic and environmental?

Answer 27

skin colour height number of offspring weight

Question 28

how does viral evolution occur?

Answer 28

Viral evolution occurs through several mechanisms, driven by the genetic variability of viruses and their interactions with hosts and environments. Here are some key processes involved in viral evolution: Mutation: Like all organisms, viruses undergo genetic mutations, which are changes in their genetic material (RNA or DNA). These mutations can arise during viral replication due to errors in the copying of genetic material or exposure to mutagenic agents. Mutations can lead to changes in viral proteins, including those involved in host cell recognition, replication, and evasion of the immune system. Recombination: Some viruses have genomes that consist of multiple segments or contain regions of repeated sequences. Recombination can occur when segments of genetic material from different viruses mix during co-infection of a host cell or through reassortment of segmented genomes. Recombination can result in the generation of novel viral strains with combinations of genetic traits from different parent viruses. Selection Pressure: Viruses face selective pressures imposed by hosts, immune responses, antiviral drugs, and environmental factors. Viral variants that are better adapted to their environment, such as those capable of evading host immune responses or resisting antiviral drugs, are more likely to survive and replicate. This selective advantage can lead to the proliferation of specific viral strains within a population. Host Range Expansion: Viruses can undergo evolutionary changes that enable them to infect new host species or adapt to new tissues or cell types within a host organism. Host range expansion can occur through mutations that enhance viral binding or entry into host cells, alter host cell tropism, or overcome host barriers to infection. Immune Evasion: Viruses can evolve mechanisms to evade host immune responses, such as by mutating viral surface proteins to evade recognition by antibodies or downregulating host immune pathways. Immune evasion strategies allow viruses to persist within host populations and contribute to ongoing viral evolution. Antiviral Resistance: Viruses can develop resistance to antiviral drugs through mutations that affect drug targets, such as viral enzymes or viral entry receptors. Resistance mutations may reduce the effectiveness of antiviral therapies and drive the emergence of drug-resistant viral strains. Epidemiological Factors: Viral evolution can be influenced by epidemiological factors such as transmission dynamics, population size, geographic spread, and patterns of human behavior. These factors can shape the frequency and spread of viral variants within and between host populations. Overall, viral evolution is a dynamic process driven by genetic variation, selective pressures, and interactions between viruses, hosts, and environments. Understanding viral evolution is essential for predicting the emergence of novel viral pathogens, designing effective vaccines and antiviral therapies, and controlling the spread of viral diseases.

Question 29

how does bacterial evolution occur?

Answer 29

During acute bacterial infections, bacterial evolution can occur rapidly, driven by the selective pressures imposed by the host immune response, antibiotic treatment, and the microenvironment within the host. Here's how bacterial evolution may unfold during an acute infection: Adaptation to Host Environment: Upon entering the host, bacteria encounter a new environment with different nutrient availability, pH levels, temperature, and immune defenses. Bacteria may undergo rapid changes in gene expression and metabolism to adapt to these conditions, allowing them to colonize host tissues and evade immune detection. Immune Evasion: Bacteria face selective pressures from the host immune system, which mounts a defense against the invading pathogens. Bacterial variants with mutations or other adaptations that allow them to evade immune detection or clearance are more likely to survive and proliferate within the host. This can lead to the emergence of bacterial strains with altered surface antigens, reduced susceptibility to phagocytosis, or enhanced ability to resist immune effectors. Antibiotic Resistance: If antibiotics are used to treat the infection, bacteria may evolve resistance to the antimicrobial agents through mechanisms such as mutation, horizontal gene transfer, or selection of pre-existing resistant variants. Antibiotic-resistant bacteria can emerge rapidly within a bacterial population under selective pressure from antibiotic treatment, leading to treatment failure and prolonged infection. Quorum Sensing and Virulence Regulation: Bacteria often use quorum sensing to coordinate the expression of virulence factors, which are molecules that enable them to colonize host tissues, evade immune defenses, and cause tissue damage. Evolutionary changes in quorum sensing systems or virulence regulation can influence the severity and outcome of the infection, as well as the host response to the bacteria. Genetic Diversity and Competition: Within the host, bacterial populations may exhibit genetic diversity due to mutation, horizontal gene transfer, or pre-existing genetic variation. This diversity can lead to competition between bacterial variants for limited resources within the host environment, shaping the dynamics of the infection and influencing the outcome of the disease. Evolutionary Trade-Offs: Bacteria may face trade-offs between traits such as virulence, antibiotic resistance, and metabolic efficiency. Evolutionary changes that enhance one trait may come at the expense of others, leading to complex dynamics within bacterial populations during infection. Overall, bacterial evolution during acute infection is a dynamic process driven by genetic variation, selective pressures, and interactions with the host environment. Understanding the mechanisms of bacterial evolution is crucial for developing effective strategies for infection control, antibiotic stewardship, and the treatment of infectious diseases.