Lecture 19. The Neutral Theory of Evolution Flashcards
What were two problems for early population geneticists ?
- Comparisons between species were impossible
2. Observable traits are more likely to have an impact on fitness
What were early population geneticists restricted to ?
Phenotypic observations
In terms of population genetics what were do problems for evolutionary biologists ?
- Morphological classification is subjective and not very amenable to mathematical models
- Limited number of traits can be securely compared
- For distant species there may be no possible traits to securely compare
- Morphological evolution is driven by natural selection and environmental selection. This can lead to convergent evolution and homoplasles mistaken by homologies
What is the strongest force in evolution ?
Selection
What are populations shaped by ?
Environmental change on both the morphological and the molecular level
What is the ultimate source of genetic variation ?
Mutation
What sort of role does mutation play in evolution ?
A minor role
What are most mutations ?
Advantageous or deleterious
How are polymorphisms maintained ?
By balancing selection
Is genetic drift relevant in panselectionism ?
No
What is the neo-Darwinian model ?
Panselection
What were the first studies of molecular variation ?
Blood
What was Goodman’s Experiments ?
- Injected blood serum into rabbits to produce an immune response and human specific antibodies
- He then compared how reactive these human specific antibodies were to blood serum proteins from different apes
What were the results of Goodman’s Experiments ?
The higher the reactivity the closer the relationship. He had a measure of molecular distance
What was the first characterisation of molecular disease ?
Sickle cell anaemia
What did Fred Sanger do in 1962 ?
Determines the amino acid sequence of insulin and demonstrates that proteins are linear polymers
What is sequencing ?
Determining the order of the chemical subunits in a linear polymer
What did the first proteins show ?
High conservation across distant species
What did Zuckerkandl and Pauling measure in 1962?
The molecular distance between pairs of haemoglobin molecules from different species by counting the number of amino acid differences
What did the number of amino acid differences correlate well with ?
The estimated divergence time from fossil record
What is the molecular clock ?
The number of amino acid differences between species correlates extremely well with their estimated divergence time from the fossil record
What do we need to calibrate the molecular clock ?
One absolute divergence time taken from an independent source
What are the steps involved in calibrating the molecular clock ?
- Count the differences between a pair of species with a known divergence time from the fossil record
- Assuming constant rate of change we can then estimate unknown divergence time between species from the number of differences
What is a substitution event ?
A new allele arises by mutation and then goes on to reach fixation
What is the equation for initial frequency ?
1/2N
What is speciation ?
Permanent reproductive isolation
Who proposed the neutral theory of evolution ?
Kimuta
What did Kimura propose ?
That most observed genetic variation is selectively neutral
Do neutral alleles have an impact on the organisms fitness ?
No
When do neutral alleles change in frequency ?
By genetic drift alone
How do most substitution events occur ?
Substitution
What did Hubby and Lewontin in 1966 do ?
Used gels to compare the same proteins from different drosphilia populations
What is neutrifying/purifying selection ?
A silent but powerful force keeping the status quo at loci of functional importance
What is a neutral allele chance of fIxation equal to ?
Its frequency
What is the symbol for the mutation rate ?
Mew
What is the mutation rate ?
The frequency at which new mutations arise in a single gene or individual over time
What is the rate of neutral evolution ?
The rate at which neutral alleles arise and become fixed in the population
What is the rate of neutral evolution known as ?
Rate of neutral substitution
What is the equation of the rate of neutral substitution ?
Number of new neutral mutations x probability of fixation
What are some impacts of an amino acid substitution ?
- The biochemical properties of the new amino acid
2. The level of functional constraint
What is the functional constraint ?
Parts of protein vital for function are more highly conserved
What is an example of functional constraint ?
Haemoglobin
What part of haemoglobin is highly constrained ?
The amino acid sequence that forms the haeme pocket
What is the function of the part of the rest of the amino acid sequence that does not form the haeme pocket ?
Constrained to be hydrophyllic
What are fibrinopeptides cleaved from ?
Fibrinogen
What is the function of fibrinopeptides ?
To activate blood clot formation
What are some of the fastest evolving proteins known ?
Fibrinopeptides
What do high levels of functional constraint slow down ?
The rate of substitution
What is redundancy in the genetic code ?
Most amino acids are coded for by many triplets, this means that some nucleotide substitutions will not result in an amino acid substitution
What is dN ?
The proportion of non-synonymous substitutions at sites where non-synonymous mutations are possible
What is dS ?
The proportion of synonymous substitutions at sites where synonymous mutations are possible. This can be taken as a proxy for the rate of neutral evolution
What can the dS/dN ratio tell us ?
Whether an entire sequence is evolving neutrally or if there is a functional constraint
What does dN/dS = 1 imply ?
All non-synonymous mutations in genes are neutral. Functional constraint is low
What does dN/dS < 1 indicate ?
Negative or purifying selection against non-synonymous mutations in the gene - functional constraint is high
What does dN/dS > 1 indicate ?
More positive selection than purifying selection for non-synonymous mutations
What has purifying selection maintained ?
Histone gene sequences in diverse eukaryotes
What is required in the histone octamer ?
Two copies of H4
What forms the complex that DNA binds into in the chromatin ?
Highly specific interactions with other histones
What are the differences in humans and wheat ?
55 DNA differences in protein coding sequences and 2 amino acid differences
