Effect of epistasis and linkage on fixation probability in three-locus models: An ancestral recombination–selection graph approach

Kermany, Amir R.; Lessard, Sabin

doi:10.1016/j.tpb.2012.05.002

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…Testing this prediction requires modifier-of-recombination theory (e.g. Otto and Barton 1997;Martin et al 2006;Roze and Barton 2006;Kermany and Lessard 2012). While we expect evolution towards the optimal recombination rate in a deterministic model (Lenormand and Otto 2000), it will be important to determine if and under which conditions this occurs in a stochastic model, and what the consequences for polygenic adaptation are.…”

Section: Non-zero Optimal Recombination Ratementioning

confidence: 99%

The Effect of Linkage on Establishment and Survival of Locally Beneficial Mutations

Aeschbacher

Bürger

2014

Genetics

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We study invasion and survival of weakly beneficial mutations arising in linkage to an established migration–selection polymorphism. Our focus is on a continent–island model of migration, with selection at two biallelic loci for adaptation to the island environment. Combining branching and diffusion processes, we provide the theoretical basis for understanding the evolution of islands of divergence, the genetic architecture of locally adaptive traits, and the importance of so-called “divergence hitchhiking” relative to other mechanisms, such as “genomic hitchhiking”, chromosomal inversions, or translocations. We derive approximations to the invasion probability and the extinction time of a de novo mutation. Interestingly, the invasion probability is maximized at a nonzero recombination rate if the focal mutation is sufficiently beneficial. If a proportion of migrants carries a beneficial background allele, the mutation is less likely to become established. Linked selection may increase the survival time by several orders of magnitude. By altering the timescale of stochastic loss, it can therefore affect the dynamics at the focal site to an extent that is of evolutionary importance, especially in small populations. We derive an effective migration rate experienced by the weakly beneficial mutation, which accounts for the reduction in gene flow imposed by linked selection. Using the concept of the effective migration rate, we also quantify the long-term effects on neutral variation embedded in a genome with arbitrarily many sites under selection. Patterns of neutral diversity change qualitatively and quantitatively as the position of the neutral locus is moved along the chromosome. This will be useful for population-genomic inference. Our results strengthen the emerging view that physically linked selection is biologically relevant if linkage is tight or if selection at the background locus is strong.

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Section: Non-zero Optimal Recombination Ratementioning

confidence: 99%

The Effect of Linkage on Establishment and Survival of Locally Beneficial Mutations

Aeschbacher

Bürger

2014

Genetics

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“…However, this work has been largely focused on the effects of single nucleotide changes. Although the simultaneous occurrence of two or more new mutations within a single gene may be rare in populations of moderate effective size and mutation rate, over many replicative events multiple mutations can accumulate on the same genetic background with potentially important consequences on, for example, the individual probabilities of fixation (Hill and Robertson 1966;Campos 2004;de Oliveira et al 2008;Kermany and Lessard 2012). This was first considered by Bateson (1909), who coined the term epistasis in what was one of the first joint considerations of Darwinian evolution with Mendelian genetics.…”

Section: Introductionmentioning

confidence: 99%

A Systematic Survey of an Intragenic Epistatic Landscape

Bank

Hietpas

Jensen

et al. 2014

Molecular Biology and Evolution

126

138

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Mutations are the source of evolutionary variation. The interactions of multiple mutations can have important effects on fitness and evolutionary trajectories. We have recently described the distribution of fitness effects of all single mutations for a nine-amino-acid region of yeast Hsp90 (Hsp82) implicated in substrate binding. Here, we report and discuss the distribution of intragenic epistatic effects within this region in seven Hsp90 point mutant backgrounds of neutral to slightly deleterious effect, resulting in an analysis of more than 1,000 double mutants. We find negative epistasis between substitutions to be common, and positive epistasis to be rare--resulting in a pattern that indicates a drastic change in the distribution of fitness effects one step away from the wild type. This can be well explained by a concave relationship between phenotype and genotype (i.e., a concave shape of the local fitness landscape), suggesting mutational robustness intrinsic to the local sequence space. Structural analyses indicate that, in this region, epistatic effects are most pronounced when a solvent-inaccessible position is involved in the interaction. In contrast, all 18 observations of positive epistasis involved at least one mutation at a solvent-exposed position. By combining the analysis of evolutionary and biophysical properties of an epistatic landscape, these results contribute to a more detailed understanding of the complexity of protein evolution.

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“…However, this work has been largely focused on the effects of single nucleotide changes. Whereas the simultaneous occurrence of two or more new mutations within a single gene may be rare in populations of moderate effective size and mutation rate, over many replicative events multiple mutations can accumulate on the same genetic background with potentially important consequences on, for example, the individual probabilities of fixation (Hill and Robertson 1966;Campos 2004;de Oliveira et al 2008;Kermany and Lessard 2012). This was first considered by Bateson (Bateson 1909), who coined the term epistasis in what was one of the first joint considerations of Darwinian evolution with Mendelian genetics.…”

Section: Introductionmentioning

confidence: 99%

A systematic survey of an intragenic epistatic landscape

Bank

Hietpas

Jensen

et al. 2014

Preprint

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Mutations are the source of evolutionary variation. The interactions of multiple mutations can have important effects on fitness and evolutionary trajectories. We have recently described the distribution of fitness effects of all single mutations for a nine-amino-acid region of yeast Hsp90 (Hsp82) implicated in substrate binding. Here, we report and discuss the distribution of intragenic epistatic effects within this region in seven Hsp90 point mutant backgrounds of neutral to slightly deleterious effect, resulting in an analysis of more than 1,000 double mutants. We find negative epistasis between substitutions to be common, and positive epistasis to be rare-resulting in a pattern that indicates a drastic change in the distribution of fitness effects one step away from the wild type. This can be well explained by a concave relationship between phenotype and genotype (i.e., a concave shape of the local fitness landscape), suggesting mutational robustness intrinsic to the local sequence space. Structural analyses indicate that, in this region, epistatic effects are most pronounced when a solvent-inaccessible position is involved in the interaction. In contrast, all 18 observations of positive epistasis involved at least one mutation at a solvent-exposed position. By combining the analysis of evolutionary and biophysical properties of an epistatic landscape, these results contribute to a more detailed understanding of the complexity of protein evolution.

show abstract

Effect of epistasis and linkage on fixation probability in three-locus models: An ancestral recombination–selection graph approach

Cited by 6 publications

References 38 publications

The Effect of Linkage on Establishment and Survival of Locally Beneficial Mutations

The Effect of Linkage on Establishment and Survival of Locally Beneficial Mutations

A Systematic Survey of an Intragenic Epistatic Landscape

A systematic survey of an intragenic epistatic landscape

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