Topic 10 Neutral Theory and Molecular Population Genetics

• predicted there would be very little genetic variation w/in and among populations • little heterozygosity

• Predicted that Balancing selection would be predominant, and heterozygosity would be high • Balancing sel’n: any form of sel’n that acts to maintain variation

-balance hypothesis won

• Selectionionists: argued that selection is responsible for maintaining high genetic variations, -selection is largely responsible for the patterns observed w/in and among pop’s and species • Neutralists: argues that most of the variation is nature is neutral (does not affect fitness). - Most of the variations are due to the interactions b/w neutral mutations and genetic drift - due to drift randomly fixing neutral mutations

• the replacement of one amino acid, or nucleotide for another in the entire populations (or species) • this leads to fixed differences b/w pop’s or species

the segregation of two or more variants (alleles) of a gene or protein in a pop’n or species -when 2 or more variants or more clearly diff phenotypes exist in the same pop’n

-a given gene or protein evolves at a constant rate -

• organisms with similar generation times have a molecular clock • Wen Hsiung Li demonstrated this • organisms with small gen. time have a high mutations’year, and vice versa • but if you look at organisms with similar gen time, there is a molecular clock

• suggested that organisms with higher metabolic rates will have higher mutations rate (due to mutagenic effect of radicals from aerobic respiration) • Problem: metabolic rate correlate w/ gen times and difficult to separate the effects of each

• Neutral theory predicts that heterozygosity increases as a function of pop’n size • why: F^= 1/ (4Ne*u +1) and H^= 1 - F^

• drosophila melanogaster exhibits a latitudinal cline in the ADH locus • proved neutralists wrong: they argued that there should be no env. correlations among loci

• a very important DNA region will evolve very slowly • e.g. catalytic site (i.e. CO1 rxn site, histones) -Neutral theory predicts that diff DNA regions evolve at diff rates based on fxnal constraints

• type of functional constraint • nonfunctional genes which evolve very rapidly • arise by gene duplications and lose their fxn • actually happens this way

• genetic code is degenerate; neutral theory predicts: 1. 4-fold degenerate sites will evolve more quickly than 2-fold degenerate sites 2. third codon pos’n will evolve more quickly than first pos’n sites. Second codon pos’n sites will evolve the slowest

• codon usage is highly non-random. This is why all synonymous mut’ns are not neutral, and diff codons for the same a.a. are not used equally • genes expressed the most will have the strongest codon bias –>reason: if silent mut’n creates a codon who’s tRNA is rare • codon bias is weak or non-existent in genes which are rarely expressed

• based on premise that slightly deleterious mut’ns can drift to fixation (or to high frequencies) • accounts for many inconsistencies w/ neutral theory • also many cases where selection has been important

• the removal of deleterious mutations - since most mut’ns are deleterious, purifying sel’n is common

Selection for favourable mut’ns that increase fitness (responsible for adaptive evolution)

Any form of sel’n that acts to maintain two or more variables at a locus • sometimes called diversifying sel’n • ex: overdominance (heterozygote superiority), frequency dependent selection

a/c= b/d –>w/in spp under the null hypothesis of neutrality a) the number of fixed non-synonymous substitutions b/w 2 species b) the number of polymorphic non-synonymous sites w/in the 2 species c) the number of fixed synonymous sites b/w the 2 species d) the number of polymorphic synonymous sites w/in 2 species • This test requires DNA sequence data that represents the sequence diversity w/in two different species • adequate sample size is critical • note: polymorphic site: many codons vs. substitution which is one codon

• given a data set, maximum likelihood methods select a model that maximizes the prob. of observing the data • computationally very intensive methods

• important to use markers that are “neutral” (not under selection) • otherwise, it will screw up the data -must be non-coding e.g. microsatellites

the merging of genealogical lineages as we trace them backward in time -note: w/ small pop’n size (historically speaking), you see more rapid coalescence than historically speaking large pop’n size