Hill-Robertson interference - senecio7の日記

Weissman DB & Barton NH 2012 Limits to teh rate of adaptive substitution in sexual populations. PLoS Genet 8:e1002740.

when multiple beneficial mutations arise simultaneously, they will typically occur in different individuals and will compete against each other, slowing adaptation
recombination (sex) alleviates this interference among mutations by bringing them together in the same individuals
interference prevents the rate of adaptive substitutions from greatly exceeding one substitution per centimorgan in every 200 generations
in these populations, the rate of adaptive substitutions is hardly affected by increasing the mutation supply or the strength of selection, but grows proportionally (up to very high rates) as recombination increases

beneficial alleles may be spreading simultaneously at multiple genetic loci
new beneficial mutations usually arise in different individuals, and thus compete with each other for fixation
in asexual populations, this "clonal interference" among alleles can drastically reduce the rate of adaptation
in sexual populations, recombination can speed adaptation by breaking up negative associations among beneficial alleles
there has been surprisingly little explicit treatment of the effects of interference on rates of adaptation
there has been intense interest in adaptation by asexual populations, stimulated by laboratory selection experiments on bacteria
this has led on to theoretical studies of multilocus evolution in sexual populations
these have generally focused on unlinked loci in facultative sexuals
not much is known quantitatively about the effect of interference among beneficial mutations in sexual populations
it is plausible that it is significant
it is important both to understand how linkage among beneficial alleles affects adaptation, and how it can be detected in natural populations from sequence data

in sufficiently large populations, Λ is proportional to R but nearly independent of the rate at which beneficial mutations are produced (NU)
adaptation is primarily limited by the rate at which recombination can bring beneficial alleles together

effective population size (as measured by heterozygosity) is a decreasing function of actual population size in moderately large populations
this can be understood by noting that when population size is large, as we assume, the rate of sampling drift is negligible, and neutral diversity must be determined primarily by selective sweeps
while increasing N increases the number of sweeps, it also decreases the effect of each sweep on neutral diversity, because of the factor of log(2Ns) in Eq. (9) which arises from the increase in the time to sweep

neutral diversity will be substantially reduced (Y≪N) when the rate of sweeps reaches Λ ~ R / (Ns), a far lower rate of sweeps than is necessary to interfere with adaptive alleles (Λ ~ R) for Ns≫1
sweeps at unlinked loci affect neutral and adaptive alleles similarly
closely-linked loci are generally likely to be the main cause of draft
at low densities of sweeps, neutral diversity is much more affected by sweeps than is fixation probability
some populations (experiencing weak interference) may be able to adapt much more rapidly than would be expected from measurements of "N_e" based on heterozygosity

lumping drift and interference together in a single number in this way is generally misleading
drift and unlinked variance in fitness dominate short-term stochasticity in allele trajectories
the effect of linked sweeps becomes important over longer time scales
the "effective population size" estimated from the common, old alleles that dominate heterozygosity is likely to be very different from the relevant quantity for rare, young alleles