explaining the evolution of sex and recombination/media/people/new-fellows-2014/... ·...

Explaining the evolution ofsex and recombination

Peter Keightley

Institute of Evolutionary BiologyUniversity of Edinburgh

Sexual reproduction is ubiquitous in eukaryotes

Meiosis with recombination

Syngamy

Sex and recombination have potential disadvantages

● Meiotic recombination breaks apart combinations of genes that have been built up by selection.

Sex and recombination have potential disadvantages

● Meiotic recombination breaks apart combinations of genes that have been built up by selection.

● Sexual reproduction requiresfinding a mate, which carries risks.

Sex and recombination have potential disadvantages

● Meiotic recombination breaks apart combinations of genes that have been built up by selection.

● Sexual reproduction requiresfinding a mate, which carries risks.

● Sex can carry a two-fold costif population growth is limited bythe number of females.

● Why are sex andrecombination almostubiquitous in nature?

● Why are sex andrecombination almostubiquitous in nature?

● Why don’t asexualstake over sexualpopulations?

Is there a general explanation for the evolution of recombination?

Collaborator: Sally OttoUniversity of British Columbia

Association between beneficial (+) and deleterious alleles (-)

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Four chromosomes in a population

Association between beneficial (+) and deleterious alleles (-)

● Alleles at the loci are negatively associated.● The coupling types ++ and -- are absent.

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Association between beneficial (+) and deleterious alleles (-)

● Alleles at the loci are negatively associated.● The coupling types ++ and -- are absent.

● The effectiveness of selection acting on variation at the loci is weakened.

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m

m

m

m

Mutations that increase recombination are favoured if there are negative allelic associations

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M

m

m

m

Mutations that increase recombination are favoured if there are negative allelic associations

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M

m

m

m+ + M

● A mutation (M) at a linked locus that increases recombination is favoured because it hitchhikes on chromosomes carrying multiple beneficial alleles, generated by recombination.

Mutations that increase recombination are favoured if there are negative allelic associations

Felsenstein & Yokoyama 1976

Non-random associations between linked loci arise in two ways

1. Directional selection.

size is very large.+ +

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Rapidly fixed

Rapidly eliminated

Non-random associations between linked loci arise in two ways

1. Directional selection.

size is very large.- +

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Non-random associations between linked loci arise in two ways

1. Directional selection.

size is very large.

Pop. size

Disequilibrium

BUT non-random associations are expected to be absent in large populations if there is some recombination.

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Non-random associations between linked loci arise in two ways

2. Synergistic epistatic interactions between loci.

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Unfit combination that is rapidly eliminated

Non-random associations between linked loci arise in two ways

2. Synergistic epistatic interactions between loci.

BUT there is little empirical evidence for this kind of epistasis.

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Is recombination favoured in the presence of selection at multiple linked loci?

Simulating the fate of a recombination modifier in the presence of selection and mutation at multiple linked loci

Population of N haploid individuals at equilibrium between linked deleterious mutations and selection.

Introduce a mutation that increases recombination.Frequency = 1/N

Simulating the fate of a recombination modifier in the presence of selection and mutation at multiple linked loci

M

M

Possible fate of a recombination modifier mutation

Modifier lost

M

MM MMM

Possible fate of a recombination modifier mutation

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M

M

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MMM

M

MMMMM

MMM

Modifier lost

Modifier fixed

● Happens at a frequency of 1/N by chance

Modifiers mutations that increase recombination were always observed to be

favoured

Recombination is strongly favoured in nonrecombining systems

0 0.25 0.5 0.75 11

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Initial recombination rate (map length, L)

Relative fixation rate of modifier

Recombination modifier increasing map length by 0.1M

The advantage of recombination increases with population size

0 5000 10000 15000 20000 250000.1

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L = 0L = 0.1L = 1

Population size, N

Relative fixation rate of modifier

Map length

The advantage of recombination increases with population size

0 5000 10000 15000 20000 250000.1

1

10

100

L = 0L = 0.1L = 1

Population size, N

● This property “emerges” because of the multi-locus nature of the model.

● In systems with small numbers of loci, recombination is favoured only in small populations.

Relative fixation rate of modifier

Map length

Why does the advantage of a recombination modifier increase with population size?

● Selection generates multi-locus associations.

Why does the advantage of a recombination modifier increase with population size?

● Selection generates multi-locus associations.

● Large populations maintain more polymorphic loci, and more negative associations, increasing the hitchhiking effect favouring recombination modifier mutations.

Why does the advantage of a recombination modifier increase with population size?

● Selection generates multi-locus associations.

● Large populations maintain more polymorphic loci, and more negative associations, increasing the hitchhiking effect favouring recombination modifier mutations.

● The infinite population prediction that negative associations should be absent does not apply when there are multiple loci under selection.

Summary

● Simple simulations show that interference between selected mutations favours mutations that increase recombination.

Summary

● Simple simulations show that interference between selected mutations favours mutations that increase recombination.

● Theory developed for two- or three-locus systems proved to be misleading.

Summary

● Simple simulations show that interference between selected mutations favours mutations that increase recombination.

● Theory developed for two- or three-locus systems proved to be misleading.

● The mechanism described is likely to be the general explanation for the evolution of recombination.

Mutations affecting fitness are universal and natural populations tend to be very large.