Genetic hitchhiking

Abstract

Selection on one or more genes inevitably perturbs other genes, even when those genes have no direct effect on fitness. This article reviews the theory of such genetic hitchhiking, concentrating on effects on neutral loci. Maynard Smith and Haigh introduced the classical case where the perturbation is due to a single favourable mutation. This is contrasted with the apparently distinct effects of inherited variation in fitness due to loosely linked loci. A model of fluctuating selection is analysed which bridges these alternative treatments. When alleles sweep between extreme frequencies at a rate lambda, the rate of drift is increased by a factor (1 + E[1/pq]lambda/(2(2lambda + r))), where the recombination rate r is much smaller than the strength of selection. In spatially structured populations, the effects of any one substitution are weaker, and only cause a local increase in the frequency of a neutral allele. This increase depends primarily on the rate of recombination relative to selection (r/s), and more weakly, on the neighbourhood size, Nb = 4(pi rho sigma)2. Spatial subdivision may allow local selective sweeps to occur more frequently than is indicated by the overall rate of molecular evolution. However, it seems unlikely that such sweeps can be sufficiently frequent to increase significantly the drift of neutral alleles.

Supergenes and their role in evolution

“…Kopp and Hermisson (2006) additionally study the effects of linkage on the evolution of genetic architecture, finding that where loci are initially tightly linked (ro0.1), several loci could be maintained as polymorphic. Increasing linkage between such loci can evolve if the selection coefficient is greater than the recombination rate between loci (Barton, 2000). In summary, theory implies that rearrangements such as inversions and perhaps even long-range translocations may have a role in supergene evolution, and importantly these ideas are now directly testable with genomic data.…”

Genetic hitchhiking in spatially extended populations

“…Kim and Maruki (2011) consider higher migration rates, but their analysis is restricted to the case when the population is subdivided into just two demes. Barton (2000) derives the increase of a linked neutral allele due to a sweep through a continuous twodimensional habitat, using a deterministic analysis forwards in time. Here, we focus on the effect of a sweep on coalescence, backwards in time, and in a spatially continuous habitat.…”

Lytic phages obscure the cost of antibiotic resistance in Escherichia coli

“…We therefore suggest that hypermutable drug-resistant genetic backgrounds will typically lie in the white region of Figure 2. We note that hitchhiking effects may be disrupted by recombination (Barton, 2000), and that mutator advantage under parasitism also depends on ecological factors such as the structure of the abiotic environment (Gómez and Buckling, 2013). Nevertheless, our finding that an elevated mutation rate is advantageous under phage selection is also consistent with evidence that Pseudomonas fluorescens mutators are favoured during coevolution with phage F2 (Pál et al, 2007;O'Brien et al, 2013).…”

“…Upon exposure to a lytic virus, phage-resistance mutations that occur stochastically on different genetic backgrounds are highly beneficial, indirectly favouring other alleles on the same genome because of genetic hitchhiking (Maynard Smith and Haigh, 1974;Barton, 2000), a process that has been demonstrated in microbes in other contexts (Morgan et al, 2012;Waite and Shou, 2012). Our model and experiments suggest that the likelihood of an antibiotic-resistant genetic background spreading under phage selection depends on the cost of antibiotic resistance in terms of intrinsic growth rate (c), the initial frequencies of different genetic backgrounds (j) and the ratio of their genomic mutation rates (n/m), because these parameters contribute directly to the relative supply rates of phageresistance mutations.…”

“…We use a nonhomogenous birthdeath process to incorporate the probability that a given phage-resistance mutation will not go extinct because of stochastic fluctuations while it is rare (Parzen, 1999, section 7.5), and this probability is itself influenced by the cost of antibiotic resistance in terms of intrinsic bacterial growth rate. We focussed on the case where one of the two genetic backgrounds fixes via genetic hitchhiking with a phage-resistance mutation (Maynard Smith and Haigh, 1974;Barton, 2000), and analysed the influence of costs of antibiotic resistance, mutation rates and initial genotype frequencies on the conditional probability that the antibiotic-resistant background fixes.…”