Molecular Genetics

Three genomic signatures of past selection

1. selective sweeps

2. dN/dS comparisons

3. Fst outlier mapping

Regulatory evolution

changes in how a gene expressed rather than changes in the coding sequence of the gene itself

Selective sweeps

selection on a beneficial allele sweeps that allele to fixation so fast that there is little opportunity for recombination to allow it to go to fixation independently of alleles at nearby loci

Genetic hitchhiking

an allele increases in frequency because it is physically linked to a positively selected allele tat a nearby loci, genes with no benefit or even a cost can be swept

Genetic linkage

physical proximity of different loci on the same chromosome, in which alleles are less likely to be separated by recombination

Areas with low genetic diversity ——————————

often bracket a positive allele that was swept to fixation

Substitution rate only reflects

mutations that go to fixation

Neutral theory of molecular evolution by Kimura

most genetic variation in natural populations is the result of genetic drift at loci that do not influence the phenotype, because selection would act on beneficial or deleterious genes

Synonymous substitutions

nucleotide changes that do not alter the amino acid sequence and have no phenotypic effect

Non-synonymous substitutions

nucleotide changes that alter the amino acid sequence and will alter a protein, which can have a range of small to large effects on the phenotype

Where does molecular evolution happen more quickly, synonymous sites or non-synonymous sites?

Synonymous sites

Practice question: why does the substitution rate tend to be higher at synonymous sites than at non-synonymous sites?

most non-synonymous mutations are deleterious

Comparing dN/dS

tests whether the non-synonymous sites have experienced selection

dN

rate of non-synonymous substitutions per non-synonymous site

dS

rate of synonymous substitutions per synonymous site

dN = dS

neutral evolution, non-synonymous substitutions are as common as expected for alleles subject to genetic drift

dN > dS

positive selection, favors new non-synonymous substitutions and they are more common than expected for alleles subject to drift

dN < dS

purifying selection, removes new non-synonymous substitutions and they are less expected for alleles subject to genetic drift

F_st

measures the discrepancy between frequency of heterozygotes expected in mating occurred separately with each sub-population (H_s) versus the frequency expected if sub-populations freely mated (H_t)

Most divergence when calculating F_st is ——————

due to drift, but outliers would suggest selection acting differently on sub-populations

How are major evolutionary changes in body form achieved?

a combination of gradual accumulation of hundreds of mutations with minor effects and major changed in a few key developmental regulators

Richard Goldschmidt 

proposed that large macro-mutations were the key to major evolutionary changes rather than gradual accumulation, ideas ridiculed as hopeful monsters

Gain-of-function mutations

adds expression to the past of the body where it is not normally expressed

Loss-of-function mutations

removes expression in body part where it is normally expressed

Homeotic genes

regulates morphology during development and include Hox and ParaHox genes in animals and MADS-box genes in plants

Hox genes

group of homeotic genes arranged sequentially in a region of DNA that control embryonic development along the anterior-posterior axis

How did Hox genes evolve?

Gene duplication of a Hox-like gene

Gene duplication

a new copy of an existing gene arises by mutation

Isopods

forward-walking crustaceans

Amphipods

forward and reverse walking crustaceans

decapods

ten legged crustaceans 

CRISPR knockout

shows what appendage would occur if one gene was knocked out of expression

Homologs

genes that are the same due to shared ancestry, can be paralogs and orthologs

Paralogs

copies formed from gene duplication within a individual or species

Orthologs

genes that occur in different species but have a homologous ancestral structure, that often have different names because they were found and named independently