The Evolutionary Advantage of Recombination

The controversy over the evolutionary advantage of recombination initially discovered by Fisher and by Muller is reviewed. Those authors whose models had finite-population effects found an advantage of recombination, and those whose models had infinite populations found none. The advantage of recombination is that it breaks down random linkage disequilibrium generated by genetic drift. Hill and Robertson found that the average effect of this randomly-generated linkage disequilibrium was to cause linked loci to interfere with each other's response to selection, even where there was no gene interaction between the loci. This effect is shown to be identical to the original argument of Fisher and Muller. It also predicts the "ratchet mechanism" discovered by Muller, who pointed out that deleterious mutants would more readily increase in a population without recombination. Computer simulations of substitution of favorable mutants and of the long-term increase of deleterious mutants verified the essential correctness of the original Fisher-Muller argument and the reality of the Muller ratchet mechanism. It is argued that these constitute an intrinsic advantage of recombination capable of accounting for its persistence in the face of selection for tighter linkage between interacting polymorphisms, and possibly capable of accounting for its origin.     

Selection for Linkage Modification II. a Recombination Balance for Neutral Modifiers

A stable polymorphic equilibrium may be established at a selectively-neutral gene locus which controls the extent of recombination between two other selected loci. The condition for the existence of the stable polymorphism is analogous to heterozygous advantage. The heterozygote at the modifying locus should produce a recombination fraction allowing the greatest linkage disequilibrium. In the models treated this has the effect of producing the highest mean fitness. The relationship of these findings to general problems of coadaptation is discussed.     

Evolutionary Consequences of Mutation and Selection within an Individual

Whether in sexual or asexual organisms, selection among cell lineages during development is an effective way of eliminating deleterious mutations. Using a mathematical analysis, we find that relatively small differences in cell replication rates during development can translate into large differences in the proportion of mutant cells within the adult, especially when development involves a large number of cell divisions. Consequently, intraorganismal selection can substantially reduce the deleterious mutation rate observed among offspring as well as the mutation load within a population, because cells rather than individuals provide the selective ``deaths' necessary to stem the tide of deleterious mutations. The reduction in mutation rate among offspring is more pronounced in organisms with plastic development than in those with structured development. It is also more pronounced in asexual organisms that produce multicellular rather than unicellular offspring. By effecting the mutation rate, intraorganismal selection may have broad evolutionary implications; as an example, we consider its influence on the evolution of ploidy levels, finding that cell-lineage selection is more effective in haploids and tends to favor their evolution.     

Genetic Change of Recombination Value in DROSOPHILA MELANOGASTER. II. Simulated Natural Selection

Selection of Gl-Sb coupling heterozygotes was carried out for more than one hundred generations commencing with six independent lines drawn from a common base population. Population sizes were eight, sixteen and forty-eight parents per generation. The effect of natural selection on recombination value was measured by sampling and testing females at varying intervals of time. There was a significant reduction in percentage recombination between Gl and Sb from fifteen to a level between five and ten in four out of six of the original lines. In most cases this reduction occurred rather rapidly after the initiation of the experiment. In the remaining two lines there was no significant decrease in recombination value; there was, however, a significant increase in at least one subline of this group. The rapid rate of change of recombination value is most readily explained by the presence of a recombination modifying gene which is linked to the modified region. Genetic random drift was again shown to have an important effect on changes in recombination value in small populations. High recombination was almost completely recessive to low recombination in the one case examined. Lethal genes were fixed in sheltered regions of unmarked third chromosomes in five lines or sublines. These results are discussed in relation to the mode of development of permanent heterozygosity in some species of plants.     

Selection for Male Recombination in DROSOPHILA MELANOGASTER

Two-way selection for male recombination over seven intervals of the third chromosome in Drosophila melanogaster was practiced for nine generations followed by relaxed selection for five generations. Significant responses in both directions were observed but these mainly occurred in early generations in the low line and in later generations in the high line. Divergence of male recombination frequencies between the two selection lines was not restricted to any specific region but occurred in every measured interval of the chromosome. However, right-arm intervals showed a more pronounced response than either left-arm intervals or the centromeric region. Correlated responses in sterility and distortion of transmission ratios occurred as a result of selection for male recombination. Cluster distributions of male recombinants suggested a mixture of meiotic and late gonial events but relative map distances more closely resembled those of the salivary chromosome than standard meiotic or mitotic distances. Patterns of male recombination over time in both second and third chromosomes strongly suggested a major effect associated with the presence of third chromosomes from the Harwich strain. Evidence was also found for modifiers with relatively small effects located in other regions of the genome. The overall results are interpreted in terms of a two-component model of hybrid dysgenesis.     

The Population and Evolutionary Dynamics of Homologous Gene Recombination in Bacteria

In bacteria, recombination is a rare event, not a part of the reproductive process. Nevertheless, recombination—broadly defined to include the acquisition of genes from external sources, i.e., horizontal gene transfer (HGT)—plays a central role as a source of variation for adaptive evolution in many species of bacteria. Much of niche expansion, resistance to antibiotics and other environmental stresses, virulence, and other characteristics that make bacteria interesting and problematic, is achieved through the expression of genes and genetic elements obtained from other populations of bacteria of the same and different species, as well as from eukaryotes and archaea. While recombination of homologous genes among members of the same species has played a central role in the development of the genetics and molecular biology of bacteria, the contribution of homologous gene recombination (HGR) to bacterial evolution is not at all clear. Also, not so clear are the selective pressures responsible for the evolution and maintenance of transformation, the only bacteria-encoded form of HGR. Using a semi-stochastic simulation of mutation, recombination, and selection within bacterial populations and competition between populations, we explore (1) the contribution of HGR to the rate of adaptive evolution in these populations and (2) the conditions under which HGR will provide a bacterial population a selective advantage over non-recombining or more slowly recombining populations. The results of our simulation indicate that, under broad conditions: (1) HGR occurring at rates in the range anticipated for bacteria like Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, and Bacillus subtilis will accelerate the rate at which a population adapts to environmental conditions; (2) once established in a population, selection for this capacity to increase rates of adaptive evolution can maintain bacteria-encoded mechanisms of recombination and prevent invasion of non-recombining populations, even when recombination engenders a modest fitness cost; and (3) because of the density- and frequency-dependent nature of HGR in bacteria, this capacity to increase rates of adaptive evolution is not sufficient as a selective force to provide a recombining population a selective advantage when it is rare. Under realistic conditions, homologous gene recombination will increase the rate of adaptive evolution in bacterial populations and, once established, selection for higher rates of evolution will promote the maintenance of bacteria-encoded mechanisms for HGR. On the other hand, increasing rates of adaptive evolution by HGR is unlikely to be the sole or even a dominant selective pressure responsible for the original evolution of transformation.     

The Coalescent Process in Models with Selection and Recombination

The statistical properties of the process describing the genealogical history of a random sample of genes at a selectively neutral locus which is linked to a locus at which natural selection operates are investigated. It is found that the equations describing this process are simple modifications of the equations describing the process assuming that the two loci are completely linked. Thus, the statistical properties of the genealogical process for a random sample at a neutral locus linked to a locus with selection follow from the results obtained for the selected locus. Sequence data from the alcohol dehydrogenase (Adh) region of Drosophila melanogaster are examined and compared to predictions based on the theory. It is found that the spatial distribution of nucleotide differences between Fast and Slow alleles of Adh is very similar to the spatial distribution predicted if balancing selection operates to maintain the allozyme variation at the Adh locus. The spatial distribution of nucleotide differences between different Slow alleles of Adh do not match the predictions of this simple model very well.     

The Definition and Measurement of Individual Condition in Evolutionary Studies

Over the past four decades, as the use of the term condition has become more frequent, the meaning of the term has become increasingly vague. This is especially true in evolutionary theory where condition is now equated with reproductive value, genetic quality, or defined as the ‘total pool of resources available for reproduction.’ Condition with the latter meaning is essentially impossible to measure empirically because it is associated with multiple attributes, such as nutritional state, health, experience, foraging success, ability to cope with environmental pressures, and social status, that collectively affect individual fitness. The addition of qualifying terms that often precede condition (e.g., phenotypic, energetic, and nutritional) and the usage of terms that describe an individual's state (e.g., physiological state, energetic state, and nutritional state) add confusion to the issue. It is therefore important to evaluate the meaning of condition, the limits of its usefulness, and how it can be best measured. We suggest using a more narrow definition of condition, amenable to empirical study, would benefit evolutionary and behavioral studies.     

Genetic Change of Recombination Value in DROSOPHILA MELANOGASTER. I. Artificial Selection for High and Low Recombination and Some Properties of Recombination-Modifying Genes

A high and low selection line were formed by individual selection of females on the basis of their recombination. In the high line, recombination between Gl and Sb was increased from 14.8 percent to about 30 percent in twelve generations, when a plateau was apparently reached. Realized heritability was 0.12. The absence of a response to selection for low recombination is attributed mainly to genetic random drift, and partially to directional dominance and directional gene frequencies. Natural selection was found to act against increases of recombination above a level of about twenty percent in the measured interval. High recombination tended to be recessive to low recombination. In both selected lines and unselected stocks, intervals proximal to the centromere tended to have a higher recombination variance than distal intervals.     

The Evolution of Epistasis and the Advantage of Recombination in Populations of Bacteriophage T4

Experiments reported here test two hypotheses about the evolution of recombination: first, the Fisher-Muller concept that sexual organisms respond to selection more rapidly than do asexual ones, and second, that epistasis is more likely to evolve in the absence of recombination. Populations of bacteriophage T4 were selected by the drug proflavine in discrete generations and the change in mean population fitness was monitored. Three separate selection series yielded results supporting the Fisher-Muller hypothesis. The amount of epistasis evolved was measured by partitioning the T4 map into regions and comparing the sum of the proflavine resistances of each region with the resistance of the whole. Significantly more interactions were found in phage isolated from the populations with lower total recombination than in those from populations with higher recombination. The degree to which these experiments fit preconceived notions about natural selection suggests that microorganisms may be advantageously used in other population genetics experiments.     

The Evolution of Recombination: Removing the Limits to Natural Selection

One of the oldest hypotheses for the advantage of recombination is that recombination allows beneficial mutations that arise in different individuals to be placed together on the same chromosome. Unless recombination occurs, one of the beneficial alleles is doomed to extinction, slowing the rate at which adaptive mutations are incorporated within a population. We model the effects of a modifier of recombination on the fixation probability of beneficial mutations when beneficial alleles are segregating at other loci. We find that modifier alleles that increase recombination do increase the fixation probability of beneficial mutants and subsequently hitchhike along as the mutants rise in frequency. The strength of selection favoring a modifier that increases recombination is proportional to λ(2)Sδr/r when linkage is tight and λ(2)S(3)δ r/N when linkage is loose, where λ is the beneficial mutation rate per genome per generation throughout a population of size N, S is the average mutant effect, r is the average recombination rate, and δr is the amount that recombination is modified. We conclude that selection for recombination will be substantial only if there is tight linkage within the genome or if many loci are subject to directional selection as during periods of rapid evolutionary change.     

Comparative and Evolutionary Analysis of the Bacterial Homologous Recombination Systems

Homologous recombination is a housekeeping process involved in the maintenance of chromosome integrity and generation of genetic variability. Although detailed biochemical studies have described the mechanism of action of its components in model organisms, there is no recent extensive assessment of this knowledge, using comparative genomics and taking advantage of available experimental data on recombination. Using comparative genomics, we assessed the diversity of recombination processes among bacteria, and simulations suggest that we missed very few homologs. The work included the identification of orthologs and the analysis of their evolutionary history and genomic context. Some genes, for proteins such as RecA, the resolvases, and RecR, were found to be nearly ubiquitous, suggesting that the large majority of bacterial genomes are capable of homologous recombination. Yet many genomes show incomplete sets of presynaptic systems, with RecFOR being more frequent than RecBCD/AddAB. There is a significant pattern of co-occurrence between these systems and antirecombinant proteins such as the ones of mismatch repair and SbcB, but no significant association with nonhomologous end joining, which seems rare in bacteria. Surprisingly, a large number of genomes in which homologous recombination has been reported lack many of the enzymes involved in the presynaptic systems. The lack of obvious correlation between the presence of characterized presynaptic genes and experimental data on the frequency of recombination suggests the existence of still-unknown presynaptic mechanisms in bacteria. It also indicates that, at the moment, the assessment of the intrinsic stability or recombination isolation of bacteria in most cases cannot be inferred from the identification of known recombination proteins in the genomes.     

Recombination Marks the Evolutionary Dynamics of a Recently Endogenized Retrovirus

All vertebrate genomes have been colonized by retroviruses along their evolutionary trajectory. Although endogenous retroviruses (ERVs) can contribute important physiological functions to contemporary hosts, such benefits are attributed to long-term coevolution of ERV and host because germline infections are rare and expansion is slow, and because the host effectively silences them. The genomes of several outbred species including mule deer (Odocoileus hemionus) are currently being colonized by ERVs, which provides an opportunity to study ERV dynamics at a time when few are fixed. We previously established the locus-specific distribution of cervid ERV (CrERV) in populations of mule deer. In this study, we determine the molecular evolutionary processes acting on CrERV at each locus in the context of phylogenetic origin, genome location, and population prevalence. A mule deer genome was de novo assembled from short- and long-insert mate pair reads and CrERV sequence generated at each locus. We report that CrERV composition and diversity have recently measurably increased by horizontal acquisition of a new retrovirus lineage. This new lineage has further expanded CrERV burden and CrERV genomic diversity by activating and recombining with existing CrERV. Resulting interlineage recombinants then endogenize and subsequently expand. CrERV loci are significantly closer to genes than expected if integration were random and gene proximity might explain the recent expansion of one recombinant CrERV lineage. Thus, in mule deer, retroviral colonization is a dynamic period in the molecular evolution of CrERV that also provides a burst of genomic diversity to the host population.     

Evolutionary Phylodynamics of Korean Noroviruses Reveals a Novel GII.2/GII.10 Recombination Event

Viral gastroenteritis is the most common causal agent of public health problems worldwide. Noroviruses cause nonbacterial acute gastroenteritis in humans of all ages. In this study, we investigated the occurrence of norovirus infection in children with acute gastroenteritis admitted to university hospitals in South Korea. We also analyzed the genetic diversity of the viruses and identified novel recombination events among the identified viral strains. Of 502 children with acute gastroenteritis admitted to our three hospitals between January 2011 and March 2012, genotyping of human noroviruses was performed in 171 (34%) norovirus-positive samples. Of these samples, 170 (99.5%) were in genogroup II (GII), while only one (0.5%) was in genogroup I (GI). The most common GII strain was the GII.4-2006b variant (n = 96, 56.5%), followed by GII.6 (n = 23, 13.5%), GII.12 (n = 22, 12.9%), GII.3 (n = 20, 11.8%), GII.2 (n = 6, 3.5%), GII.b (n = 2, 1.2%), and GII.10 (n = 1, 0.6%). Potential recombination events (polymerase/capsid) were detected in 39 GII strains (22.9%), and the most frequent genotypes were GII.4/GII.12 (n = 12, 30.8%), GII.4/GII.6 (n = 12, 30.8%), GII.4/GII.3 (n = 8, 20.5%), GII.b/GII.3 (n = 3, 7.7%), GII.16/GII.2 (n = 2, 5.1%), GII.4/GII.2 (n = 1, 2.6%), and GII.2/GII.10 (n = 1, 2.6%). For the first time, a novel GII.2/GII.10 recombination was detected; we also identified the GII.16/GII.2 strain for the first time in South Korea. Our data provided important insights into new recombination events, which may prove valuable for predicting the emergence of circulating norovirus strains with global epidemic potential.     

The evolution of habitat preference II. Evolutionary genetic stability under soft selection

A previous analysis of a single-locus, two-allele model of the evolution of habitat selection revealed that preference evolves toward equalization of parental investment in offspring placed in two different habitats in which population size is regulated independently (soft selection). That analysis is extended here to the case of a single locus with multiple alleles. The major result of this analysis is that regardless of how many alleles are present at equilibrium, new alleles will invade if and only if they tend to make parental investment in the two habitats more equal. In other words, the population evolves toward an Evolutionary Stable State (ESS) characterized by equalization of parental investment. The model may explain the maintenance of genetic variation for host (habitat) preference exhibited by many insect species.