Molecular Evolution Flashcards
(26 cards)
What makes a theory scientific?
- you need to make testable predictions
- they stand or fall according to whether the predictions are confirmed or refuted
(the theory needs to be falsifiable)
Describe variations.
- they are mutations due to changes in the DNA sequence
- mostly mistakes during DNA synthesis
- rare because DNA synthesis is exceedingly accurate
- most mutations are neutral or deleterious (harmful) , a minority are beneficial
Describe relative fitness (w).
It is defined as the average number of surviving progeny of a genotype (compared with competing genotypes) after one generation.
If w<1, the frequency of the allele:
- will decrease with each generation
- until the allele disappears (negative selection)
If w>1, the frequency of the allele:
- will increase with each generation
- until the allele reaches fixation (positive selection)
What is the basis of molecular phylogeny?
DNA mutations accumulate over time, so species that share a recent common ancestor will have fewer differences than species that are more distantly related.
What are the medical implications of molecular phylogeny?
Substances produced by fungi, which are toxic to bacteria, but not fungi, are called antibiotics.
For humans, antibiotics are not toxic and can be used medically. This is because there is a greater similarity between homo sapiens and fungi than there is with bacteria.
Describe the two kinds of substitution?
Synonymous Substitution: when a base substitution has no effect on the amino acid chain.
Non-synonymous Substitution: when the base substitution changes the amino acid chain, and therefore, the nucleotide.
How did myoglobin come about?
Haemoglobins (Hb) are ancient in evolution.
Duplication of an ancestral gene gave rise to myoglobin and haemoglobin.
List some differences between myoglobin and haemoglobin.
MYOGLOBIN:
- expressed in skeletal muscle
- monomeric protein
- hyperbolic oxygen dissociation curve
- function: oxygen storage
HAEMOGLOBIN:
- expressed in red blood cells
- tetrametric protein
- sigmoidal oxygen dissociation curve
- function: oxygen transport
HbF has evolved to have a higher oxygen affinity than HbA.
How did this come about?
There were changes made to the amino acid sequence of the γ globin protein.
Describe the 2 γ genes.
There are actually two gamma (foetal) genes.
The coding for the proteins differes by one amino acid.
It is not known if the proteins differ in function.
The γ genes are expressed during foetal life, while the β gene is expressed during postnatal life.
How does this occur?
The promoter is duplicated along with the coding sequence. The promoter sequence as also evolved so that the β and γ promoters now bind to different transcription factors.
They interact differently with gene enhancers, giving us a differential control of the β and γ genes.
At first, LCR (locus control region an enhancer-type element) interacts with foetal genes, giving the expression of γ genes.
Then, at birth, there are changes in transcription factors, and the LCR then interacts with β-globin promoters, giving us β gene expression.
Define pseudogenes, and give an example.
Pseudogenes are non-functional genes (they have stop codons, ridiculous amino acids etc.). They are common in DNA.
An example would be ψβ. It has a clear sequence homology to the β-globin gene, but we know it can’t make a functional protein.
After gene duplication, one gene can maintain the original function and the other can diverge
Pseudogenes typically have many mutations and are non-functional
They complicate PCR/sequencing/etc!
Describe Fanconi’s anaemia.
It is a recessive lethal genetic disorder. Most affected patients die of bone marrow failure during childhood, and if they survive, they do not reproduce.
The gene arises by random mutation and is eliminated by natural selection. It has a very low allele frequency (0.2%).
Describe SCA (Sickle Cell Anaemia).
It arises from a point mutation in the β globin gene. It is a single amino acid substitution; a hydrophilic amino acid (glutamic acid) is replaced by a hydrophobic amino acid (valine) at position 6.
The mutant haemoglobin molecules aggregate and form crystals when deoxygenated, which forces the red cells into the characteristic ‘sickle’ shape.
The crystals damage the red cell membrane, resulting in:
- cell lysis, causing anaemia
- cell adhesion causing blockage of small blood vessels, followed by tissue infarction.
Why is SCA so common compared to Fanconi’s anaemia?
J.B.S. Haldane noted that thalassaemia and SCA are common in areas of endemic malaria. He hypothesised that heterozygotes for these alleles are resistant to malaria.
There is now excellent direct evidence for improved survival of SCA heterozygote carriers (up to 95% protection), due to lower parasitaemia and fewer severe complications.
Heterozygotes can still catch malaria, but they have a much less likely chance of dying because of malaria.
What is natural selection and fitness?
the effects of a wide range of factors on the frequency of heritable changes in a species
Fitness – how well a species is able to reproduce in its environment
Anything that increases fitness is selected for, anything that decreases fitness is selected against and other neutral changes will vary randomly
What are frequencies of genetic mutation affected by?
Selection
Mutation
Migration
Genetic Drift
What is selection?
Genetic variants that confer a positive advantage will be selected for (and vice versa)
Examples might confer resistance to disease, an ability to metabolise a new food source, antibiotic resistance or a change in appearance that enhances mate choice
Some parts of the genome are resistant to change as they contain vital sequences – they are conserved
What is mutation?
The name for the process by which variation in the genome arises is mutation
We all carry large numbers of genomic variants and their frequency will depend on selection and when they first arose
A rare variant may have arisen very recently or be deleterious and being selected against or both
What is migration?
The physical movement of people from a different population results in new pools of variants being introduced to an existing population
This is called admixture
Population frequencies of specific variants can change purely due to admixture and not be disease-related.
What is genetic drift?
This is how the frequency of a variant changes in a population due to chance
Not all organisms in a population will pass on their genetic variants
Mechanisms such as recombination will also result in not all variants being passed on
All variants are subject to genetic drift
What is sequence conservation?
DNA sequence that is vital to the survival of an organism does not normally show much evidence of variation
Most variants in these regions will be selected against as they are likely to have a strongly deleterious effect
There is some flexibility for variation in the third base of codons as some amino acids are encoded by multiple codons
What types of sequences are conserved?
High conservation – coding regions (not exons as these contain non-coding regions)
Intermediate conservation – Promoter, 5’ untranslated region (UTR), 3’ UTR, terminator
Low conservation – introns, 3rd base of codons, terminator
Cross-species comparison can be used to generate an evolutionary profile for a gene or gene family
What is gene duplication?
This is duplication of a DNA sequence containing a gene
The typical mechanism is unequal crossing over during meiosis
After duplication One copy can continue the original function The other copy can evolve new function(s) by changes in the coding sequence and/or control sequences
