Genetic hitchhiking, also calledgenetic draft or thehitchhiking effect,[1] is when anallele changesfrequency not because it itself is undernatural selection, but because it isnear another gene that is undergoing aselective sweep and that is on the sameDNA chain. When one gene goes through a selective sweep, any other nearbypolymorphisms that are inlinkage disequilibrium will tend to change theirallele frequencies too.[2] Selective sweeps happen when newly appeared (and hence still rare) mutations are advantageous and increase in frequency.Neutral or even slightly deleterious alleles that happen to beclose by on the chromosome 'hitchhike' along with the sweep. In contrast, effects on a neutral locus due to linkage disequilibrium with newly appeared deleterious mutations are calledbackground selection. Both genetic hitchhiking and background selection arestochastic (random) evolutionary forces, likegenetic drift.[3]
The termhitchhiking was coined in 1974 byMaynard Smith and John Haigh.[1] Subsequently the phenomenon was studied byJohn H. Gillespie and others.[4]
Hitchhiking occurs when a polymorphism is in linkage disequilibrium with a second locus that is undergoing a selective sweep. The allele that is linked to the adaptation will increase in frequency, in some cases until it becomesfixed in the population. The other allele, which is linked to the non-advantageous version, will decrease in frequency, in some cases untilextinction.[5][6] Overall, hitchhiking reduces the amount of genetic variation. Ahitchhiker mutation (orpassenger mutation in cancer biology) may itself be neutral, advantageous, or deleterious.[7]
Recombination can interrupt the process of genetic hitchhiking, ending it before the hitchhiking neutral or deleterious allele becomes fixed or goes extinct.[6] The closer a hitchhiking polymorphism is to the gene under selection, the less opportunity there is for recombination to occur. This leads to a reduction in genetic variation near a selective sweep that is closer to the selected site.[8] This pattern is useful for using population data to detect selective sweeps, and hence to detect which genes have been under very recent selection.
Bothgenetic drift and genetic draft are random evolutionary processes, i.e. they act stochastically and in a way that is not correlated with selection at the gene in question. Drift is the change in the frequency of an allele in a population due to random sampling in each generation.[9] Draft is the change in the frequency of an allele due to the randomness of what other non-neutral alleles it happens to be found inassociation with.
Assuming genetic drift is the only evolutionary force acting on an allele, after one generation in many replicatedidealised populations each of size N, each starting with allele frequencies of p and q, the newly added variance in allele frequency across those populations (i.e. the degree of randomness of the outcome) is.[3] This equation shows that the effect of genetic drift is heavily dependent on population size, defined as the actual number of individuals in anidealised population. Genetic draft results in similar behavior to the equation above, but with aneffective population size that may have no relationship to the actual number of individuals in the population.[3] Instead, the effective population size may depend on factors such as the recombination rate and the frequency and strength of beneficial mutations. The increase in variance between replicate populations due to drift is independent, whereas with draft it is autocorrelated, i.e. if an allele frequency goes up because of genetic drift, that contains no information about the next generation, whereas if it goes up because of genetic draft, it is more likely to go up than down in the next generation.[9] Genetic draft generates a differentallele frequency spectrum to genetic drift.[10]
TheY chromosome does not undergorecombination, making it particularly prone to the fixation of deleterious mutations via hitchhiking. This has been proposed as an explanation as to why there are so few functional genes on the Y chromosome.[11]
Hitchhiking is necessary for the evolution of highermutation rates to be favored by natural selection onevolvability. A hypothetical mutator M increases the generalmutation rate in the area around it. Due to the increased mutation rate, the nearby A allele may be mutated into a new, advantageous allele, A*
--M------A-- -> --M------A*--
The individual in which this chromosome lies will now have a selective advantage over other individuals of this species, so the allele A* will spread through the population by the normal processes ofnatural selection. M, due to its proximity to A*, will be dragged through into the general population. This process only works when M is very close to the allele it has mutated. A greater distance would increase the chance of recombination separating M from A*, leaving M alone with any deleterious mutations it may have caused. For this reason, evolution of mutators is generally expected to happen largely inasexual species where recombination cannot disrupt linkage disequilibrium.[12]
Theneutral theory of molecular evolution assumes that most new mutations are either deleterious (and quickly purged by selection) or else neutral, with very few being adaptive. It also assumes that the behavior of neutral allele frequencies can be described by the mathematics of genetic drift. Genetic hitchhiking has therefore been viewed as a major challenge to neutral theory, and an explanation for why genome-wide versions of theMcDonald–Kreitman test appear to indicate a high proportion of mutations becoming fixed for reasons connected to selection.[13]