Periodic selection describes a peculiar form of microorganism response to natural selection. The peculiarity results from affected populations being clonal, that is, not participating in gene exchange (i.e., sex) with other organisms and therefore having no mechanism by which alleles may be separated nor brought together by recombination. All of the alleles within a clonal organism therefore can be described as 100% linked. A consequence of this complete linkage is that increases in the frequency of one allele, particularly a beneficial allele, can result in an increase in the frequency of any other alleles that are found in the same genome, that is, so long as those other alleles are not already fixed within the population. Gains in frequency by any one allele within a population also results in declines in any alleles not found within the same genome. Note, though, that this mechanism of adaptation works inefficiently because beneficial alleles found within different genotypes cannot be shared and even may be lost from populations should periodic selection result in the fixation of a different genotype (Levin and Bergstrom, 2000) .
Periodic selection can give rise to a sequential piecing together of newly arising, adaptive mutations into a series of most-fit genotypes, at least so long as the new, beneficial mutations driving periodic selection arise within otherwise most-fit genotypes. Alternatively, less-fit genotypes can become most-fit genotypes, and thereby selected over other genotypes found within the same environment, due to acquisition of a sufficiently beneficial mutation. It is more likely, nevertheless, that such beneficial mutations will arise within more prevalent genotypes simply because the number of new mutations that arise within a subpopulation will be a direct function of a subpopulation's size. Most-fit genotypes thus, via periodic selection, tend to become most-prevalent genotypes which in turn tend to give rise to additional, beneficial mutations. That is not always true, however, unless the most-fit genotype has become fixed within a population, thereby representing the only genetic background within which mutations can occur within a population.
Periodic selection is equivalent to selective sweeps of beneficial alleles through clonal populations. These are periodic because, in finite populations, beneficial alleles arise only episodically rather than continuously. Such alleles not only must be beneficial, but also must be sufficiently beneficial that the resulting overall genotype displays a great enough fitness that it is able to outcompete other high-fitness phenotypes found within the same population. Alternatively, a phenomenon called clonal interference can occur, where similarly fit alleles thwart each other's rise to fixation, that is, block periodic selection.
While periodic selection is an interesting idea, and likely plays roles in the evolution of microorganisms, it does have two shortcomings: (1) It is dependent upon a relative absence of spatial structure, which serves as an impediment on the movement and therefore other than local ascendance of more-fit genotypes, and (2) it is dependent on a similar dearth of horizontal gene transfer since otherwise more-fit genotypes may be gained other than via mutation. In other words, the concept of periodic selection was developed prior to a robust understanding of the frequency of gene exchange among microorganism plus was based upon experience studying microorganisms within well-mixed broth cultures. The result is a perspective on microorganism evolution that likely is more short-term and local in its impact than was originally envisaged. Nonetheless, in terms of developing an understanding of microbial evolution in general as well as the dynamics of broth-based microbial experimental evolution studies, the concept of periodic selection is important and perhaps may be viewed as a default assumption vis-à-vis the dynamics of the evolution of mostly clonal microorganisms.
Hitchhiking, or, more formally, genetic hitchhiking, is the association of the fate of one allele with that of another. This can occur whenever there is linkage between two alleles, and the more linkage then the greater the number of generations that the presence of a beneficial allele can indirectly select for increases in the prevalence of a less beneficial or even detrimental allele (i.e., as discussed under the heading of periodic selection). Indeed, the whole idea of selectively neutral markers is based upon the equivalent concept of genetic hitchhiking. Relevant to these scenarios is that beneficial alleles must arise within otherwise not-fixed genetic backgrounds for the prevalence of other alleles to increase via hitchhiking, though the basic concept of alleles following one another during selection due to linkage still holds. That is, even if hitchhiking does not give rise to changes in the frequencies of hitchhiking alleles it is still hitchhiking (just not hitchhiking that has much meaning nor which can be easily observed). In particular, what occurs is the tying together of the fates of alleles particularly with that of the overall genotype within which they are found. See (Barton, 2000) for review of genetic hitchhiking.
Periodic selection in combination with hitchhiking can have a similar impact on populations as genetic drift, that is, random changes in the prevalence of alleles, even those alleles that are beneficial. This occurs because the alleles that are linked within a genotype, whether they are neutral in their impact on organism fitness, or even detrimental, can increase in prevalence given linkage to exceptionally beneficially alleles (or, including if beneficial, can decrease in prevalence due to linkage with less-fit alleles). As a result, periodic selection in combination with genetic hitchhiking can be viewed as a mechanism that can have the overall effect of reducing the genetic diversity of populations of microorganisms. That is, as one clone increases in prevalence, particularly towards fixation, then all other otherwise closely related clones within a population must decline. Turning this idea around (p. 1554), "…because hitchhiking limits the ability of populations to respond to selection, it also generates selection for increased recombination rates."
This phenomenon has the consequence of reducing the effective population size of clonal organisms (Barton, 2000) (Levin and Bergstrom, 2000) . The result, more or less equivalently, is a population that tends to build, evolutionarily, upon one or instead only a small number of successful clones (i.e., sequential evolution), where a dominating clone, due to its high frequency, is more likely to give rise to the next population-sweeping beneficial mutation. Note, nonetheless, that because of hitchhiking it can be difficult to determine what specific allele is responsible for a selective sweep, that is, which of potentially multiple alleles that simultaneously have increased in prevalence is the beneficial allele or alleles that gave rise to a clonal sweep.
In genetic hitchhiking it is assumed that a hitchhiking allele, other than being linked to a beneficial allele, otherwise functions independently of that allele. Not all alleles are similarly independent of a given other allele. An example is seen with compensatory mutations. Here, as with hitchhiking, a deleterious allele is already present within a genome and it is followed by the acquisition of a beneficial allele, thereby increasing the fitness of the overall genotype. The difference between compensatory mutations and a more general scenario for hitchhiking, however, is that for compensatory mutations the benefit gained is dependent on the existence of a previous, deleterious mutation. Hitchhiking, thus, is a 'rising tide that raises all ships', without regard to what ships are present (that is, within a given genome). By contrast, with compensatory mutations it is a specific allele that is impacted by the beneficial effect and indeed the fitness advantage associated with the compensatory mutation may not even be present absent the first, deleterious allele.
Though linkage between alleles in general will allow genetic hitchhiking to take place, functional interdependence between alleles in fact can select for greater levels of linkage and, as a consequence, result in a sense in a greater potential for hitchhiking. A great utility of sex is its potential to break apart linkage between alleles, and thereby to a degree preventing the inadvertent selection of otherwise deleterious and even so-called "selfish" alleles (i.e., via hitchhiking) while a great problem with sex is its potential to break apart what essentially are coevolved alleles. Hitchhiking, that is, is a problem that can stem from linkage, but linkage itself can be useful, and particularly so towards the evolution of greater organism fitness through increased functional interdependence between specific alleles. Purely clonal organisms in particular can suffer greatly from an accumulation of deleterious alleles in the course of periodic selection, hitchhiking, and Muller’s Ratchet, but also can benefit greatly from the coevolution of gene complexes such as operons.
The utility of general mutator strains comes from their greater potential to be linked with mutationally acquired beneficial alleles. This increased likelihood is a result simply of general mutator strains exhibiting higher mutation rates. It also is a utility that is seen particularly given novel environmental conditions since under those circumstances beneficial mutations are more prevalent, given that change can be preferable when conditions are poor than when conditions are good.
The fitness of mutator alleles is reduced as populations approach linkage equilibrium – that is, where alleles are not linked – because the potential for the mutator allele to hitchhike with beneficial alleles is reduced under these circumstances. Periodic selection associated with acquisition of these beneficial alleles in fact will no longer efficiently operate given substantial sexual exchange of alleles within populations because most-fit genotypes within stable environments can be replaced not just as a consequence of mutation but due to gene exchange between individuals as well, where the benefits from general mutator alleles stem from mutation alone. The fitness of mutator alleles, periodic selection, and genetic hitchhiking thus can viewed as potentially co-occurring phenomena, as are periodic selection and genetic hitchhiking more generally.
Note that our previous discussions of hitchhiking have primarily been from the perspective of a neutral or deleterious allele being carried along within a genotype that contains sufficiently beneficial alleles that overall fixation occurs. In the special case of mutator alleles, it is the mutator allele that is the deleterious allele. The high mutation rates associated with mutator alleles, however, suggests an additional variation on this scenario and that is that in addition to the mutator allele hitchhiking along with beneficial alleles, so too can additional deleterious (or neutral) alleles, ones generated due to higher mutation rates hitchhike along with newly acquired beneficial alleles. That is, greater mutation rates give rise to both deleterious and beneficial alleles. Consequently, upon the rise towards fixation of an overall beneficial genotype, so too deleterious alleles may rise with greater probability towards fixation than one may observe in less mutation-prone genetic backgrounds.
Despite my calling to our attention this possible scenario, note that is may be somewhat unlikely. This is because what is being suggested is that a deleterious mutation, in addition to the general mutator allele, is followed by a beneficial mutation, rather than the other way around. If a beneficial mutation occurs first, then unless a second, deleterious mutations occurs prior to the replication of both alleles (or the singly mutated genotype otherwise fails to survive while the doubly mutated genotype lives), then it is likely that the detrimental mutation will occur in only a single carrier of the beneficial mutation. In other words, selection should favor those genotypes that carry the beneficial mutation without a second detrimental mutation. Alternatively, but less likely, a genotype carrying a detrimental mutation may, prior to its loss from a population, acquire a beneficial mutation that reverses this fate. The acquisition of such a second, beneficial mutation, however, will be unlikely if the genotype carrying the detrimental mutation is low in prevalence, as would be expected.
Given these arguments, we would have an expectation that newly arising detrimental mutations would in fact not tend to accompany beneficial mutations over the course of periodic selection, despite the possibility that this could occur. The corollary, however, is that given sufficiently high mutation rates, i.e., of greater than one mutation per genome per replication event, then it will be much less likely for beneficial mutations to increase towards fixation without carrying with them hitchhiking deleterious alleles. The result is a potential utility to the display of greater mutation rates under conditions where periodic selection operates, but with mutation rates that are greater only to a point, with that point defined in terms of the efficiency with which natural selection can act on newly arising beneficial alleles independently to counter accumulations of deleterious alleles.