molecular evolution

Lots of molecular evolution

Estimated a substitution every two years based on fossil record

Molecular evolution is

Clocklike/constant divergence that does not track with environmental change

Neutral theory

1) Too many AA substitutions have occurred for all of them to be beneficial

2) Rates of molecular change are often clocklike

• Most mutations are deleterious and are purged quickly (negative selection)

• Beneficial mutations are rare, so won’t be fixed often (positive selection)

• Most mutations that have been fixed between lineages (substitutions) therefore must be neutral and the product of drift

Negative selection

Purifying selection

Most mutations are deleterious and are purged quickly

Rare favored

Positive selection

Beneficial mutations are rare, so won’t be fixed often

The beneficial alleles can be ignored since they are not going to fixation and don’t help much

Substitutions

Most mutations that have been fixed between lineages therefore must

be neutral and the product of drift

Pseudogenes

nonfunctional copies of a gene expected to evolve neutrally since all mutations have the same fitness

dn=ds

Nonsynonmous do not affect it because this gene is nonfunctional

dn

Rate of non synonymous substitution

ds

Rate of synonymous substitution

Functional genes

weed out nonsynonous substitutions since most are deleterious so

dn < ds

Genes with conserved functions

ds »»» dn

Genes that change rapidly

dn < ds

A little bit more than usual dn because of changing due to selection

dN /dS < 1

• Most mutations are deleterious

• Negative (purifying) selection dominates

• Most functional genes

dN /dS = 1

• Mutations are neutral

• Drift dominates

• Pseudogenes

dN /dS > 1

• Mutations are beneficial

• Positive selection dominates

More functional changes being fixed to match new environment

ex. Spike proteins undergo constant change in response to environment

genes that show evidence of positive selection in mice vs. humans via dN/dS?

Immune genes since they are constantly responding to the environment

Ne, selection, and the drift-barrier hypothesis

• Multicellular organisms have low Ne, meaning drift shapes their genomes more than selection

• This explains their relatively high mutation rates and bloated genomes

McDonald-Kreitman (MK) Test

• Looks at number of synonymous and No synonymouts changes both within and among species

• Logic is that beneficial changes will spread to fixation quickly, so don’t appear within species, but do appear between species

• More sensitive at detecting positive selection than dN /dS

Ex. Positive selection for Flies with gene to help process rotten fruit

How can synonymous changes affect fitness?

Codon bias

Codon bias

• The nonrandom usage of codons

those with more efficiency are used, higher expression use one codon

• Degree of bias depends on expression level of gene

• Codons corresponding to most abundant tRNA are used most

• Selection for increased translational speed and efficiency

Background selection

Selection against deleterious alleles causing nearby alleles to decrease in frequency or be lost

Selective sweeps/genetic hitchhiking

Selection for beneficial alleles causing nearby linked alleles to rise in frequency or go to fixation

Neutral theory status

Mostly used as a null-model to tell when selection has happened