Week 7: Multivariate Evolution + Molecular Evolution

What are univariate characters?

• individual characters you can measure

• e.g drosophila bristle number or stalk-eyed fly eyespan

• Continuous distribution

• One dimension

• Univariate characters show a straightforward response to artificial selection e.g stalk eyed fly eyespan selected for → wider/ narrow

• Responses to selection due to genetic basis of phenotypes

• every trait evolves independently

• trait specific adaptation/ optimisation

What are multivariate characters?

• a trait that has evolved but hasn’t been selected for

• e.g male eyespan + female preference in stalk eyed flies

• correlated responses

• phenotypes are multi-dimensional

Pleiotropy

same genes affect more than one trait

How much can we expect a trait to change over n generations?

Breeder’s equation

R = h²S

What term is used in the Breeder’s equation to describe genetic variation for a one dimension trait?

additive genetic variance

What is used in the Breeder’s equation to describe genetic variation for 2 dimension traits/ positively correlated values?

Genetic variance-covariance matrix

What does it mean if traits do not covary?

Independent evolution – 2 univariate traits

(same as univariate Breeder’s equation)

What happens when traits covary

• interference between traits

• selection on one trait affects the other trait

Correlated responses

one trait selected, both change

Accelerated responses

positive correlation, selection aligned

Adaptive conflicts

• positive correlation, selection opposed

• positive selection on trait one, negative selection on trait 2

• ^ evolutionary stale-mates

Why does sexual dimorphism happen?

• different reproductive roles

• opposing selection pressures on a shared trait → because of differing reproductive roles→ drives sexual dimorphism

What are males reproductive roles limited by?

• limited by mating partners

• cheaper gametes

What are female reproductive roles limited by?

• expensive gametes

• limited by resources gathered

Example of opposing selection pressures on the same trait

Locomotion in D. melanogaster , Long and Rice (2007)

• genotypes with high fitness move little

• low fitness move a lot

• female fruit-fly → don’t waste time moving

• in males → positive selection for more movement → increase fitness, encounter mates

How does sexual dimorphism occur when genomes are shared between sexes?

• only part of DNA restricted is chromosome 23 or sex chromosomes - Y chromosome → in males any beneficial mutation may be fixed on Y chromosome

• on other genes → adaptive evolution happens less

• Inter-sexual genetic correlations are high

• multivariate characters

What are the two phases for the evolution of sexual dimorphism

Sexual antagonism

• Adaptive conflict between the sexes

  New mutations are

  • beneficial to one sex

  • deleterious to the other sex

• Mutations can invade if the benefits to one sex outweigh the costs in the other sex

Evidence for sexual antagonism

Chippindale et al. (2001)

• D. melanogaster

• Negative correlation between male and female fitness

• GWAS used (Ruzicka et al. 2019) → 2,372 SNPs, ~200 clusters in genome involved in adaptive conflict

Conflict resolution→ has happened since males and females are different

• via mutations that break down genetic correlation

• Mutations in regulatory regions → sex-specific gene expression

• Mutations in genic regions → sex-specific protein variants

Example of conflict resolution

Bonduriansky and Rowe (2005)

In waltzing flies

What is molecular evolution?

• Change measured at the scale of DNA, RNA or proteins.

• Hereditary variation is the medium of evolution – the result of underlying changes at the DNA level

• Track evolutionary change by examining sequence changes over time

What causes molecular evolution?

• mutations

• non-synonymous substitution → alters AA + potential to affect gene function

• The amino acid change may affect aspects of resultant protein molecule

  • folding structure, binding properties, hydrophilic/hydrophobic

How are deleterious mutations removed?

by purifying selection

How are advantageous mutations fixed?

by positive selection

Example of fixation via intense positive selection

• Tibetan plateau, extreme altitude, O₂ pressure < 2/3 of sea level value

• Plot of SNP polymorphisms for Tibetans versus Han Chinese (~sea level). Strong correlation, alleles common or rare in both populations.

• Exceptions in EPAS1 gene: 90% in T, 10% in HC

• EPAS1 gene has an allele that confers advantages at high altitudes by increasing production of red blood cells– has been selected in Tibetan population.

• Downside is that more red blood cells increases blood viscosity and risk of heart attack

Mutations that have no effect on gene function

silent/ synonymous substitutions

Molecular clock explained by neutral theory

For genes accumulating differences by drift, number of differences between 2 species is proportional to the time since their most common ancestor → a linear relation between time and divergence

Most common substitutions

• Rate of silent substitutions is higher than rate of non-synonymous substitutions.

• Among non-synonymous substitutions, changes to amino acids with similar biochemical properties (e.g. both hydrophilic) are more common than changes with greater effect on protein function.

What kind of sequences are free from purifying selection?

• non-coding sequences e,g introsn + pseudogenes

• evolve at a higher rate similar to silent sites

What kind of genes evolve more slowly?

• genes with higher functional constraints

• fewer mutations in these genes are neutral

• e.g histones are critical in fundamental processes of chromosome assembly and replication hence histone sequence and structure are slowly evolving.

Uses for the molecular clock

1. Phylogenetic relationships

2. Speciation rates

3. Divergence Times

Is the molecular clock reliable?

• Mutation rate is assumed to be constant

• Population size (Ne) assumed to be of similar magnitude at occurrence of mutation and in subsequent period of potential fixation

  • if population suffers drastic bottleneck after mutation’s occurrence, fixation more likely and clock speeds up

• Selection is assumed to be constant

  • adaptive bursts do happen e.g adaptation to a new food source

What is mutation rate affected by?

• higher metabolic rate - causes more oxidative damage to DNA = faster tick rate

• generation time - faster generation time increases number of meiotic divisions per year = faster tick rate

Example: Mammal phylogeny

• Rodents : high metabolic rate + short generation time → elevated mutation rate

Example of adaptive burst

• Rhagoletis fly

• Adaptive shift in food source from hawthorn to apple

• Changed selective regime for genes involved in host plant choice and food metabolism pathways

Studies showing the constancy of molecular evolution

The Hawaiian Molecular Clock

• Volcanic origins have produced chain of islands of increasing geological age. Molecular data confirm order of colonisation

• Example: Honeycreeper species’ phylogeny: species of oldest islands form deepest branch of tree, those of younger islands tree’s tips.

• Disparate taxa (birds/insects) show linear relationship between genetic divergence and time when DNA distance between sister species plotted against geological estimates of island age (young to old on X-axis).

d_N / d_s

relative rate of functional evolution

d_N = coding/ replacement/ non synonymous sites

d_s = silent (synonymous) sites

Life-cycle of a substitution

• Born as a mutation in one individual - it is a low frequency polymorphism

Fate

• If deleterious, tend to decrease in frequency and disappear

• If advantageous, tend to increase in frequency.

  • Persists as polymorphism until displaces all alternative alleles in population.

• Mutation → polymorphism → becomes a substitution when all alternative versions have disappeared

• When all of population carry copy of same mutation - it is fixed in population

d_N / d_s = 1

• Synonymous and non-synonymous mutations have little effect on fitness and evolve largely neutrally

• Both have similar chance of drifting through population to fixation

• Sites accumulate differences between species by random genetic drift

d_N / d_s > 1

• Many non-synonymous replacements advantageous, fixation via boost from positive selection

• Under positive selection, non-synonymous sites will evolve more quickly than neutral synonymous sites and differences between species can build up rapidly

• replacements are advantageous, fixed by positive selection

d_N / d_s < 1

• most synonymous replacement are deleterious and removed by purifying selection

• replacement are deleterious, removed by purifying selection

Example of Molecular signatures of Adaptive Change: HIV surface envelope protein

• Branch-specific d_N/d_S is elevated in those lineages with recent HIV transmission and high pathogenicity

• Suggests positive selection operating on envelope protein following recent shifts to new hosts.

  • Note that surface protein’s function is to foster viral entry into host cells

Example of Molecular Signatures of Adaptive Change: BRCA1 human gene

• Ratio is high on branches of primate phylogeny leading to chimps and humans. - What caused the positive selection? Unclear.

• BRCA1 is responsible for cases of breast cancer.

• The BRCA1 protein plays role in repair of damaged DNA, hence why mutations in gene cause cancer. Some claims that BRCA1 part of host defense against viral DNA/proteins

• Perhaps coevolution with viruses drove rapid evolution but side-effect that more likely to mutate to cancer-triggering form.

Fraction→ d_N / d_s

McDonald-Kreitman Test

• M-T test + related tests assay positive selection by extending d_N / d_S  ratio test on differences in substitutions between species, to include data on polymorphism within a focal species

• M-K test compares

  ratio of non-synonymous to synonymous polymorphisms within species

  to

  ratio of non-synonymous to synonymous substitutions between species

How does gene duplication arise?

mispairing during recombination

Pseudogene

Often build up of mis-sense and regulatory mutations→ leads to gene death

Subfunctionalisation

sometimes copy takes over one aspect of original gene function - both copies are required to carry out the job of the original gene

Neofunctionalisation

the gene copy can take on a new role entirely