The evolutionary cost of homophily: social stratification facilitates stable variant coexistence and increased rates of evolution in host-associated pathogens.

Coexistence of multiple strains of a pathogen in a host population can present significant challenges to vaccine development or treatment efficacy. Here we discuss a novel mechanism that can increase rates of long-lived strain polymorphism, rooted in the presence of social structure in a host population. We show that social preference of interaction, in conjunction with differences in immunity between host subgroups, can exert varying selection pressure on pathogen strains, creating a balancing mechanism that supports stable viral coexistence, independent of other known mechanisms. We use population genetic models to study rates of pathogen heterozygosity as a function of population size, host population composition, mutant strain fitness differences and host social preferences of interaction. We also show that even small periodic epochs of host population stratification can lead to elevated strain coexistence. These results are robust to varying social preferences of interaction, overall differences in strain fitnesses, and spatial heterogeneity in host population composition. Our results highlight the role of host population social stratification in increasing rates of pathogen strain diversity, with effects that should be considered when designing policies or treatments with a long-term view of curbing pathogen evolution.

Rapid evolution of phenotypic plasticity in patchy habitats.

Phenotypic plasticity may evolve rapidly, enabling a population's persistence in the face of sudden environmental change. Rapid evolution can occur when there is considerable genetic polymorphism at selected loci. We propose that balancing selection could be one of the mechanisms that sustain such polymorphism for plasticity. We use stochastic Monte Carlo simulations and deterministic analysis to investigate the evolution of a plasticity modifier locus in structured populations inhabiting favorable and adverse environments, i.e. patchy habitats. We survey a wide range of parameters including selective pressures on a target (structural) locus, plasticity effects, population sizes, and migration patterns between demes including periodic or continuous bidirectional and source-sink dynamics. We find that polymorphism in phenotypic plasticity can be maintained under a wide range of environmental scenarios in both favorable and adverse environments due to the balancing effect of population structure in patchy habitats. This effect offers a new plausible explanation for the rapid evolution of plasticity in nature: Phenotypic plasticity may rapidly evolve from genetic variation maintained by balancing selection if the population has experienced immigration from populations under different selection regimes.

Rapid evolution of genome-wide gene expression and plasticity during saline to freshwater invasions by the copepod Eurytemora affinis species complex.

Saline migrants into freshwater habitats constitute among the most destructive invaders in aquatic ecosystems throughout the globe. However, the evolutionary and physiological mechanisms underlying such habitat transitions remain poorly understood. To explore the mechanisms of freshwater adaptation and distinguish between adaptive (evolutionary) and acclimatory (plastic) responses to salinity change, we examined genome-wide patterns of gene expression between ancestral saline and derived freshwater populations of the Eurytemora affinis species complex, reared under two different common-garden conditions (0 versus 15 PSU). We found that evolutionary shifts in gene expression (between saline and freshwater inbred lines) showed far greater changes and were more widespread than acclimatory responses to salinity (0 versus 15 PSU). Most notably, 30-40 genes showing evolutionary shifts in gene expression across the salinity boundary were associated with ion transport function, with inorganic cation transmembrane transport forming the largest Gene Ontology category. Of particular interest was the sodium transporter, the Na+ /H+ antiporter (NHA) gene family, which was discovered in animals relatively recently. Thirty key ion regulatory genes, such as NHA paralogue #7, demonstrated concordant evolutionary and plastic shifts in gene expression, suggesting the evolution of ion transporter function and plasticity during rapid invasions into novel salinities. Moreover, freshwater invasions were associated with the evolution of reduced plasticity in the freshwater population, again for the same key ion transporters, consistent with the predicted evolution of canalization following adaptation to stressful conditions. Our results have important implications for understanding evolutionary and physiological mechanisms of range expansions by some of the most widespread invaders in aquatic habitats.

Phenotypic plasticity promotes recombination and gene clustering in periodic environments.

While theory offers clear predictions for when recombination will evolve in changing environments, it is unclear what natural scenarios can generate the necessary conditions. The Red Queen hypothesis provides one such scenario, but it requires antagonistic host-parasite interactions. Here we present a novel scenario for the evolution of recombination in finite populations: the genomic storage effect due to phenotypic plasticity. Using analytic approximations and Monte-Carlo simulations, we demonstrate that balanced polymorphism and recombination evolve between a target locus that codes for a seasonally selected trait and a plasticity modifier locus that modulates the effects of target-locus alleles. Furthermore, we show that selection suppresses recombination among multiple co-modulated target loci, in the absence of epistasis among them, which produces a cluster of linked selected loci. These results provide a novel biological scenario for the evolution of recombination and supergenes.

Phenotypic Plasticity Promotes Balanced Polymorphism in Periodic Environments by a Genomic Storage Effect.

Phenotypic plasticity is known to evolve in perturbed habitats, where it alleviates the deleterious effects of selection. But the effects of plasticity on levels of genetic polymorphism, an important precursor to adaptation in temporally varying environments, are unclear. Here we develop a haploid, two-locus population-genetic model to describe the interplay between a plasticity modifier locus and a target locus subject to periodically varying selection. We find that the interplay between these two loci can produce a "genomic storage effect" that promotes balanced polymorphism over a large range of parameters, in the absence of all other conditions known to maintain genetic variation. The genomic storage effect arises as recombination allows alleles at the two loci to escape more harmful genetic backgrounds and associate in haplotypes that persist until environmental conditions change. Using both Monte Carlo simulations and analytical approximations we quantify the strength of the genomic storage effect across a range of selection pressures, recombination rates, plasticity modifier effect sizes, and environmental periods.

Emergence of long-term balanced polymorphism under cyclic selection of spatially variable magnitude.

A fundamental question in evolutionary biology is what promotes genetic variation at nonneutral loci, a major precursor to adaptation in changing environments. In particular, balanced polymorphism under realistic evolutionary models of temporally varying environments in finite natural populations remains to be demonstrated. Here, we propose a novel mechanism of balancing selection under temporally varying fitnesses. Using forward-in-time computer simulations and mathematical analysis, we show that cyclic selection that spatially varies in magnitude, such as along an environmental gradient, can lead to elevated levels of nonneutral genetic polymorphism in finite populations. Balanced polymorphism is more likely with an increase in gene flow, magnitude and period of fitness oscillations, and spatial heterogeneity. This polymorphism-promoting effect is robust to small systematic fitness differences between competing alleles or to random environmental perturbation. Furthermore, we demonstrate analytically that protected polymorphism arises as spatially heterogeneous cyclic fitness oscillations generate a type of storage effect that leads to negative frequency dependent selection. Our findings imply that spatially variable cyclic environments can promote elevated levels of nonneutral genetic variation in natural populations.

Signatures of recent directional selection under different models of population expansion during colonization of new selective environments.

A major problem in population genetics is understanding how the genomic pattern of polymorphism is shaped by natural selection and the demographic history of populations. Complex population dynamics confounds patterns of variation and poses serious challenges for identifying genomic imprints of selection. We examine patterns of polymorphism using computer simulations and provide analytical predictions for hitchhiking effects under two models of adaptive niche expansion. The population split (PS) model assumes the separation of a founding population followed by directional selection in the new environment. Here, the new population undergoes a bottleneck and later expands in size. This model has been used in previous studies to account for demographic effects when testing for signatures of selection under colonization or domestication. The genotype-dependent colonization and introgression (GDCI) model is proposed in this study and assumes that a small number of migrants carrying adaptive genotype found a new population, which then grows logistically. The GDCI model also allows for constant migration between the parental and the new population. Both models predict reduction in variation and excess of high frequency of derived alleles relative to neutral expectations, with and without hitchhiking. Under comparable conditions, the GDCI model results in greater reduction in expected heterozygosity and more skew of the site frequency spectrum than the PS model. We also find that soft selective sweeps (fixation of multiple copies of a beneficial mutation) occurs less often in the GDCI model than in the PS model. This result demonstrates the importance of correctly modeling the ecological process in inferring adaptive evolution using DNA sequence polymorphism.

Inferring purging from pedigree data.

The harmful effects of inbreeding can be reduced if deleterious recessive alleles were removed (purged) by selection against homozygotes in earlier generations. If only a few generations are involved, purging is due almost entirely to recessive alleles that reduce fitness to near zero. In this case the amount of purging and allele frequency change can be inferred approximately from pedigree data alone and are independent of the allele frequency. We examined pedigrees of 59,778 U.S. Jersey cows. Most of the pedigrees were for six generations, but a few went back slightly farther. Assuming recessive homozygotes have fitness 0, the reduction of total genetic load due to purging is estimated at 17%, but most of this is not expressed, being concealed by dominant alleles. Considering those alleles that are currently expressed due to inbreeding, the estimated amount of purging is such as to reduce the expressed load (inbreeding depression) in the current generation by 12.6%. That the reduction is not greater is due mainly to (1) generally low inbreeding levels because breeders in the past have tended to avoid consanguineous matings, and (2) there is essentially no information more than six generations back. The methods used here should be applicable to other populations for which there is pedigree information.