Fixation Of Alleles Research Articles

Two Lineages of KLRA with Contrasting Transcription Patterns Have Been Conserved at a Single Locus during Ruminant Speciation.

Cattle possess the most diverse repertoire of NK cell receptor genes among all mammals studied to date. Killer cell receptor genes encoded within the NK complex and killer cell Ig-like receptor genes encoded within the leukocyte receptor complex have both been expanded and diversified. Our previous studies identified two divergent and polymorphic KLRA alleles within the NK complex in the Holstein-Friesian breed of dairy cattle. By examining a much larger cohort and other ruminant species, we demonstrate the emergence and fixation of two KLRA allele lineages (KLRA*01 and -*02) at a single locus during ruminant speciation. Subsequent recombination events between these allele lineages have increased the frequency of KLRA*02 extracellular domains. KLRA*01 and KLRA*02 transcription levels contrasted in response to cytokine stimulation, whereas homozygous animals consistently transcribed higher levels of KLRA, regardless of the allele lineage. KLRA*02 mRNA levels were also generally higher than KLRA*01 Collectively, these data point toward alternative functional roles governed by KLRA genotype and allele lineage. On a background of high genetic diversity of NK cell receptor genes, this KLRA allele fixation points to fundamental and potentially differential function roles.

Selective Sweeps Under Dominance and Inbreeding.

A major research goal in evolutionary genetics is to uncover loci experiencing positive selection. One approach involves finding ‘selective sweeps’ patterns, which can either be ‘hard sweeps’ formed by de novo mutation, or ‘soft sweeps’ arising from recurrent mutation or existing standing variation. Existing theory generally assumes outcrossing populations, and it is unclear how dominance affects soft sweeps. We consider how arbitrary dominance and inbreeding via self-fertilization affect hard and soft sweep signatures. With increased self-fertilization, they are maintained over longer map distances due to reduced effective recombination and faster beneficial allele fixation times. Dominance can affect sweep patterns in outcrossers if the derived variant originates from either a single novel allele, or from recurrent mutation. These models highlight the challenges in distinguishing hard and soft sweeps, and propose methods to differentiate between scenarios.

Historical Introgressions from a Wild Relative of Modern Cassava Improved Important Traits and May Be Under Balancing Selection.

Introgression of alleles from wild relatives has often been adaptive in plant breeding. However, the significance of historical hybridization events in modern breeding is often not clear. Cassava (Manihot esculenta) is among the most important staple foods in the world, sustaining hundreds of millions of people in the tropics, especially in sub-Saharan Africa. Widespread genotyping makes cassava a model for clonally propagated root and tuber crops in the developing world, and provides an opportunity to study the modern benefits and consequences of historical introgression. We detected large introgressed Manihot glaziovii genome-segments in a collection of 2742 modern cassava landraces and elite germplasm, the legacy of a 1930s era breeding to combat disease epidemics. African landraces and improved varieties were, on average, 3.8% (max 13.6%) introgressed. Introgressions accounted for a significant (mean 20%, max 56%) portion of the heritability of tested traits. M. glaziovii alleles on the distal 10 Mb of chr. 1 increased dry matter and root number. On chr. 4, introgressions in a 20 Mb region improved harvest index and brown streak disease tolerance. We observed the introgression frequency on chr. 1 double over three cycles of selection, and that later stage trials selectively excluded homozygotes from consideration as varieties. This indicates a heterozygous advantage of introgressions. However, we also found that maintaining large recombination-suppressed introgressions in the heterozygous state allowed the accumulation of deleterious mutations. We conclude that targeted recombination of introgressions would increase the efficiency of cassava breeding by allowing simultaneous fixation of beneficial alleles and purging of genetic load.

Genetic diversity in Calibrachoa pygmaea (Solanaceae): A hawkmoth-pollinated nightshade from the Pampas

ABSTRACT Calibrachoa pygmaea is a unique species of Calibrachoa, especially concerning its flower morphology and the environment where it occurs. The species is self-incompatible and is narrowly distributed in wet and flooded fields of the Pampas region. We characterize the genetic diversity of the species based on traditional plastid markers and newly developed nuclear microsatellites to identify drivers that guide its evolution. Our results identified markers that are informative and useful for studying the population structure of C. pygmaea, as well as that of other species of Calibrachoa. Both marker sets were congruent in developing conclusions regarding the evolutionary scenario of C. pygmaea, and revealed that the genetic variability and population structure of the species could be explained by common allele fixation or shared ancestral polymorphism, while its diversification can be attributed mainly to the species’ dispersal ability and certain ecological features.

Assessment of Genetic Diversity of Narra (Pterocarpus indicus Willd.) Populations From Various Seed Sources in the Philippines Using RAPD

Pterocarpus indicus Willd. (narra), a critically endangered group, is one of the priority species for conservation and reforestation in the Philippines due to its economic, industrial, and ecological importance. A range of 29 to 40 individual samples from each of six seed sources from the Philippines were tested for genetic diversity using 11 RAPD markers. A total of 134 loci were detected, 129 of which were polymorphic. The mean genetic diversity within population was found to be moderate at 0.3183, which could be attributed to the deciduous and outcrossing nature of narra. The genetic differentiation among populations (0.0575) and Wright’s Fixation Index (0.1528) suggests nearness of the populations to each other and distance from fixation of alternative alleles in the populations. The genetic distance and cluster analysis did not conform to geographical distribution, but revealed the relationships and the possible origin/s of the individuals of the populations. The results of the study is useful in the selection of sources of good planting materials for the improvement of narra tree in the Philippines.

Genomic analysis unveils important aspects of population structure, virulence, and antimicrobial resistance in Klebsiellaaerogenes.

Klebsiellaaerogenes is an important pathogen in healthcare-associated infections. Nevertheless, in comparison to other clinically important pathogens, K.aerogenes population structure, genetic diversity, and pathogenicity remain poorly understood. Here, we elucidate K.aerogenes clonal complexes (CCs) and genomic features associated with resistance and virulence. We present a detailed description of the population structure of K.aerogenes based on 97 publicly available genomes by using both multilocus sequence typing and single-nucleotide polymorphisms extracted from the core genome. We also assessed virulence and resistance profiles using Virulence Finder Database and Comprehensive Antibiotic Resistance Database, respectively. We show that K.aerogenes has an open pangenome and a large effective population size, which account for its high genomic diversity and support that negative selection prevents fixation of most deleterious alleles. The population is structured in at least 10 CCs, including two novel ones identified here, CC9 and CC10. The repertoires of resistance genes comprise a high number of antibiotic efflux proteins as well as narrow- and extended-spectrum β-lactamases. Regarding the population structure, we identified two clusters based on virulence profiles because of the presence of the toxin-encoding clb operon and the siderophore production genes, irp and ybt. Notably, CC3 comprises the majority of K.aerogenes isolates associated with hospital outbreaks, emphasizing the importance of constant monitoring of this pathogen. Collectively, our results may provide a foundation for the development of new therapeutic and surveillance strategies worldwide.

Genetic diversity and population structure of founders from wildlife conservation management units and wild populations of critically endangered Dermatemys mawii

Many endangered freshwater turtle species are born in captivity for conservation and future reintroduction into the wild. However, in order to improve breeding programs, an assessment of the genetic diversity of the founder individuals is required to avoid genetic problems such as inbreeding, fixation of deleterious alleles, or loss of allelic diversity due to genetic drift. In this research, we assessed the genetic diversity of the founder individuals from three Wildlife Management Units (UMA) dedicated to the reproduction of Dermatemys mawii in southeast Mexico, and from three wild populations using ten microsatellite markers. Dermatemys mawii is a freshwater turtle that is critically endangered due principally to fragmentation, loss, degradation, and contamination of its habitat, in addition to hunting for human consumption. Furthermore, genetic relationships among UMAs and wild populations, as well as within each kind of group, were investigated by means of Bayesian analysis (Structure software) and discriminant analysis of principal component (DAPC). Genetic diversity in wild populations could be considered as medium, and are less than values observed for UMAs. Genetic diversity for UMAs and wild populations were discussed considering origin of individuals, translocation between UMAs, habitat quality among other factors. Genetic structure analysis highlighted an evident separation between UMAs and wild populations (Bayesian and DAPC analyses), and the hierarchical analysis of structure among UMAs reflected the origin and relationship among them, whereas geographical situation of wild populations is the best explanation for its hierarchical structure. In light of our results, some conservation and management recommendations are provided for this endangered freshwater turtle.

Allele fixation probability in a Moran model with fluctuating fitness landscapes.

Evolution on changing fitness landscapes (seascapes) is an important problem in evolutionary biology. We consider the Moran model of finite population evolution with selection in a randomly changing, dynamic environment. In the model, each individual has one of the two alleles, wild type or mutant. We calculate the fixation probability by making a proper ansatz for the logarithm of fixation probabilities. This method has been used previously to solve the analogous problem for the Wright-Fisher model. The fixation probability is related to the solution of a third-order algebraic equation (for the logarithm of fixation probability). We consider the strong interference of landscape fluctuations, sampling, and selection when the fixation process cannot be described by the mean fitness. Such an effect appears if the mutant allele has a higher fitness in one landscape and a lower fitness in another, compared with the wild type, and the product of effective population size and fitness is large. We provide a generalization of the Kimura formula for the fixation probability that applies to these cases. When the mutant allele has a fitness (dis-)advantage in both landscapes, the fixation probability is described by the mean fitness.

SSR Based Genetic Diversity Analysis in Diploid Algaroba (Prosopis spp.) Population

Algaroba (Prosopis palida and Prosopis juliflora species) provides important environmental and economic benefits for semi-arid regions of the world. These are resistant to drought, and its fruits are used in the manufacture of flour and algarobina syrup. In the present study, the chromosome number, the ploidy level, and the genetic diversity based on 40 microsatellite loci of Prosopis spp. were determined in samples of a Brazilian algaroba population. The cytogenetic analysis in the metaphase showed only diploid individuals (2n = 28), with multiple cells featuring two CMA3/DAPI- heterochromatic blocks suggesting diploid level. However, polysomatism was found by the presence of some cells with four CMA3/DAPI- blocks, showing the tetraploid level just in some somatic cells. Among all of the primers tested for cross-amplification in algaroba, 22 were selected to characterize the samples. Thirteen loci revealed allele polymorphisms in the population and are recommended for future population studies and genetic improvement. The mean values of the analyzes showed low genetic diversity (two alleles per locus and HE = 0.181), reflecting the history of the introduction of algaroba in this sampled locality, and suggesting the genetic bottleneck and probable events of founders, as well as the characteristics of the species of this genera. However, amplified loci indicated low inbreeding (allelic fixation index of -0.007), although heterozygosis was higher than expected by the Hardy-Weinberg equilibrium. Therefore, this algaroba population is formed by diploid individuals and adjusts to the tendency of low number of alleles per locus SSR commonly observed in different species of Prosopis.

Neutral Genetic and Phenotypic Variation within and among Isolated Headwater Populations of Brook Trout

AbstractIsolated populations are challenging to manage and conserve, as they are particularly vulnerable to genetic drift, allelic fixation, and inbreeding and may express markedly reduced phenotypic variability. We sought to improve our understanding of how spatial isolation, occupancy range, and restricted gene flow influence contemporary phenotypic variation within and among native populations of Brook Trout Salvelinus fontinalis by examining the neutral genetic and phenotypic characteristics of 35 isolated headwater populations from Great Smoky Mountains National Park. Across a suite of 13 neutral microsatellite loci, we observed high levels of allelic fixation and considerable genetic differentiation among populations, subwatersheds, and watersheds that were consistent with patterns of isolation. We found significant positive correlations between allelic diversity and estimates of effective population size. In contrast, we observed considerably less phenotypic structure among streams, subwatersheds, and watersheds. Much of the observed phenotypic variation occurred among individuals within populations. Pairwise Mann–Whitney tests revealed no significant phenotypic differences among the populations of Brook Trout we examined. Similarly, there was no significant relationship between the amount of phenotypic variation within populations and any of the examined measures of genetic diversity or the amount of occupied habitat sampled, which suggests that unmeasured variables may be influencing morphometric and meristic variation within isolated populations. The observed patterns of isolation, genetic drift, and allelic fixation highlight the importance of enhancing population connectivity but also suggest that considerable phenotypic variability may persist within small, fragmented populations. Our results elucidate some challenges associated with managing and conserving isolated populations of Brook Trout and reinforce the importance of conducting genetic studies on fragmented populations to inform management decisions.

Haplotype Loci Under Selection in Canadian Durum Wheat Germplasm Over 60 Years of Breeding: Association With Grain Yield, Quality Traits, Protein Loss, and Plant Height.

Durum wheat was introduced in the southern prairies of western Canada in the late nineteenth century. Breeding efforts have mainly focused on improving quality traits to meet the pasta industry demands. For this study, 192 durum wheat lines were genotyped using the Illumina 90K Infinium iSelect assay, and resulted in a total of 14,324 polymorphic SNPs. Genetic diversity changed over time, declining during the first 20 years of breeding in Canada, then increased in the late 1980s and early 1990s. We scanned the genome for signatures of selection, using the total variance Fst-based outlier detection method (Lositan), the hierarchical island model (Arlequin) and the Bayesian genome scan method (BayeScan). A total of 407 outliers were identified and clustered into 84 LD-based haplotype loci, spanning all 14 chromosomes of the durum wheat genome. The association analysis detected 54 haplotype loci, of which 39% contained markers with a complete reversal of allelic state. This tendency to fixation of favorable alleles corroborates the success of the Canadian durum wheat breeding programs over time. Twenty-one haplotype loci were associated with multiple traits. In particular, hap_4B_1 explained 20.6, 17.9 and 16.6% of the phenotypic variance of pigment loss, pasta b∗ and dough extensibility, respectively. The locus hap_2B_9 explained 15.9 and 17.8% of the variation of protein content and protein loss, respectively. All these pleiotropic haplotype loci offer breeders the unique opportunity for further improving multiple traits, facilitating marker-assisted selection in durum wheat, and could help in identifying genes as functional annotations of the wheat genome become available.

Gene flow simulations demonstrate resistance of long-lived species to genetic erosion from habitat fragmentation

Habitat fragmentation restricts the movement of individuals across a landscape. In terrestrial and aquatic systems, barriers to movement can modify population and community dynamics at local or regional scales. This study contrasted life history traits related to lifespan with habitat fragmentation to determine impacts on species population genetic structure in the Neuse River Basin, USA. For this, we simulated gene flow among evenly-spaced populations in a river network and tracked individual and population genetics for 200 years. The modeled scenarios represent a full cross between five life history strategies and four riverscapes representing varying degrees of fragmentation. The five life history strategies include species (based on freshwater mussels) with average lifespans ranging from 10 to 50 years and age at maturity from 2 to 6 years. The movement landscapes included a (1) panmictic, (2) stepping-stone landscape allowing movement to only neighboring populations during each dispersal event, (3) partially-fragmented landscape divided by dams currently in the network, and (4) fully-fragmented landscape. Results suggest species with shorter lifespans have higher population genetic structure in fragmented landscapes than species with longer lifespans. Furthermore, species with shorter lifespans in highly fragmented landscapes may be harboring genetic degradation or decline as allele fixation and loss. Although anthropogenic fragmentation of many river systems is only 100–200 years old, the simulation indicates that species can respond genetically in that period of time. Additionally, the time frame of the simulation suggests that genetic impacts of habitat fragmentation in some species present in the Neuse River Basin may not yet be manifesting and restoration activities could be successful.

Haploids, polymorphisms and fluctuating selection

I analyze the joint impact of directional and fluctuating selection with reversible mutation in finite bi-allelic haploid populations using diffusion approximations of the Moran and chemostat models. Results differ dramatically from those of the classic Wright–Fisher diffusion. There, a strong dispersive effect attributable to fluctuating selection dissipates nascent polymorphisms promoted by a relatively weak emergent frequency dependent selective effect. The dispersive effect in the Moran diffusion with fluctuations every birth–death event is trivial. The same frequency dependent selective effect now dominates and polymorphism is promoted. The dispersive effect in the chemostat diffusion with fluctuations every generation is identical to that in the Wright–Fisher diffusion. Nevertheless, polymorphism is again promoted because the emergent frequency dependent effect is doubled, an effect attributable to geometric reproduction within generations. Fluctuating selection in the Moran and chemostat diffusions can also promote bi-allelic polymorphisms when one allele confers a net benefit. Rapid fluctuations within generations are highly effective at promoting polymorphism in large populations. The bi-allelic distribution is approximately Gaussian but becomes uniform and then U-shaped as the frequency of environmental fluctuations decreases to once a generation and then once every multiple generations. Trade-offs (negative correlations in fitness) help promote polymorphisms but are not essential. In all three models the frequency dependent effect raises the probability of ultimate fixation of new alleles, but less effectively in the Wright–Fisher diffusion. Individual-based forward simulations confirm the calculations.

Effects of demographic stochasticity and life-history strategies on times and probabilities to fixation.

How life-history strategies influence the evolution of populations is not well understood. Most existing models stem from the Wright-Fisher model which considers discrete generations and a fixed population size, thus not taking into account any potential consequences of overlapping generations and demographic stochasticity on allelic frequencies. We introduce an individual-based model in which both population size and genotypic frequencies at a single bi-allelic locus are emergent properties of the model. Demographic parameters can be defined so as to represent a large range of r and K life-history strategies in a stable environment, and appropriate fixed effective population sizes are calculated so as to compare our model to the Wright-Fisher diffusion. Our results indicate that models with fixed population size that stem from the Wright-Fisher diffusion cannot fully capture the consequences of demographic stochasticity on allele fixation in long-lived species with low reproductive rates. This discrepancy is accentuated in the presence of demo-genetic feedback. Furthermore, we predict that populations with K life-histories should maintain lower genetic diversity than those with r life-histories.

Population Structure and Genetic Diversity Within the Endangered Species Pityopsis ruthii (Asteraceae).

Pityopsis ruthii (Ruth’s golden aster) is a federally endangered herbaceous perennial endemic to the Hiwassee and Ocoee Rivers in southeastern Tennessee, United States. Comprehensive genetic studies providing novel information to conservationists for preservation of the species are lacking. Genetic variation and gene flow were evaluated for 814 individuals from 33 discrete locations using polymorphic microsatellites: seven chloroplast and twelve nuclear. A total of 198 alleles were detected with the nuclear loci and 79 alleles with the chloroplast loci. Gene flow was estimated, with the Hiwassee River (Nm = 2.16; FST = 0.15) showing higher levels of gene flow and lower levels of population differentiation than the Ocoee River (Nm = 1.28; FST = 0.19). Population structure was examined using Bayesian cluster analyses. Nuclear and chloroplast analyses were incongruent. From the chloroplast microsatellites, three clusters were identified; all were present in sampling sites at both rivers, indicating a lack of allele fixation along rivers. Nuclear markers revealed two clusters and separated by river. When the Hiwassee River locations were analyzed, four clusters were identified for both the chloroplast and nuclear microsatellites, though the individuals clustered differently. Analysis of the Ocoee River revealed two clusters for the chloroplast microsatellites and three for the nuclear microsatellites. We recommend P. ruthii be managed as four populations for the Hiwassee River and three populations for the Ocoee River. Our results provide critical genetic information for P. ruthii that can be used for species management decisions to drive future population augmentation/reintroduction and ex situ conservation efforts.

Mendelian Transmission Ratio Distortion (TRD) and Factors Determining the Low Frequency of the t-Haplotypes in Wild Populations of the House Mouse Mus musculus of Russia and the Neighboring Countries of Eurasia

The results of analysis of the frequencies of t-alleles and heterozygous +/t individuals of house mice of different subspecies (musculus, bactrianus, tataricus, wagneri, and gansuensis) are presented for the natural populations inhabiting eight cities and five regions of Russia and adjacent countries of Eastern Europe and Asia. It is shown that the frequencies of t-alleles are 0.18 ± 0.03 in small samples (1–30 individuals) and 0.09 ± 0.06 in medium-sized samples (31–60 individuals). The factors that reduce the frequencies of t-alleles in natural populations and the mechanisms that prevent invasion and fixation of t-mutant alleles in the Mus musculus genome are discussed.

Mutations in EID1 and LNK2 caused light-conditional clock deceleration during tomato domestication

Circadian period and phase of cultivated tomato (Solanum lycopersicum) were changed during domestication, likely adapting the species to its new agricultural environments. Whereas the delayed circadian phase is mainly caused by allelic variation of EID1, the genetic basis of the long circadian period has remained elusive. Here we show that a partial deletion of the clock gene LNK2 is responsible for the period lengthening in cultivated tomatoes. We use resequencing data to phylogenetically classify hundreds of tomato accessions and investigate the evolution of the eid1 and lnk2 mutations along successive domestication steps. We reveal signatures of selection across the genomic region of LNK2 and different patterns of fixation of the mutant alleles. Strikingly, LNK2 and EID1 are both involved in light input to the circadian clock, indicating that domestication specifically targeted this input pathway. In line with this, we show that the clock deceleration in the cultivated tomato is light-dependent and requires the phytochrome B1 photoreceptor. Such conditional variation in circadian rhythms may be key for latitudinal adaptation in a variety of species, including crop plants and livestock.

Sex chromosomes and speciation in birds and other ZW systems.

Theory and empirical patterns suggest a disproportionate role for sex chromosomes in evolution and speciation. Focusing on ZW sex determination (females ZW, males ZZ; the system in birds, many snakes, and lepidopterans), I review how evolutionary dynamics are expected to differ between the Z, W and the autosomes, discuss how these differences may lead to a greater role of the sex chromosomes in speciation and use data from birds to compare relative evolutionary rates of sex chromosomes and autosomes. Neutral mutations, partially or completely recessive beneficial mutations, and deleterious mutations under many conditions are expected to accumulate faster on the Z than on autosomes. Sexually antagonistic polymorphisms are expected to arise on the Z, raising the possibility of the spread of preference alleles. The faster accumulation of many types of mutations and the potential for complex evolutionary dynamics of sexually antagonistic traits and preferences contribute to a role for the Z chromosome in speciation. A quantitative comparison among a wide variety of bird species shows that the Z tends to have less within-population diversity and greater between-species differentiation than the autosomes, likely due to both adaptive evolution and a greater rate of fixation of deleterious alleles. The W chromosome also shows strong potential to be involved in speciation, in part because of its co-inheritance with the mitochondrial genome. While theory and empirical evidence suggest a disproportionate role for sex chromosomes in speciation, the importance of sex chromosomes is moderated by their small size compared to the whole genome.

Tetrad analysis in plants and fungi finds large differences in gene conversion rates but no GC bias.

GC-favoring gene conversion enables fixation of deleterious alleles, disturbs tests of natural selection and potentially explains both the evolution of recombination as well as the commonly reported intra-genomic correlation between G+C content and recombination rate. In addition, gene conversion disturbs linkage disequilibrium, potentially affecting the ability to detect causative variants. However, the importance and generality of these effects is unresolved, not simply because direct analyses are technically challenging but also because prior within- and between-species discrepant results can be hard to appraise owing to methodological differences. Here we report results of methodologically uniform whole-genome sequencing of all tetrad products in Saccharomyces, Neurospora, Chlamydomonas and Arabidopsis. The proportion of polymorphic markers converted varies over three orders of magnitude between species (from 2% of markers converted in yeast to only ~0.005% in the two plants) with at least 87.5% of the variance in per tetrad conversion rates being between-species. This is largely owing to differences in recombination rate and median tract length. Despite three of the species showing a positive GC-recombination correlation, there is no significant net AT->GC conversion bias in any, despite relatively high resolution in the two taxa (Saccharomyces and Neurospora) with relatively common gene conversion. The absence of a GC bias means: 1) that there should be no presumption that gene conversion is GC biased, nor 2) that a GC-recombination correlation necessarily implies biased gene conversion, 3) that Ka/Ks tests should be unaffected in these species and 4) it is unlikely that gene conversion explains the evolution of recombination.

Survival and divergence in a small group: The extraordinary genomic history of the endangered Apennine brown bear stragglers

About 100 km east of Rome, in the central Apennine Mountains, a critically endangered population of ∼50 brown bears live in complete isolation. Mating outside this population is prevented by several 100 km of bear-free territories. We exploited this natural experiment to better understand the gene and genomic consequences of surviving at extremely small population size. We found that brown bear populations in Europe lost connectivity since Neolithic times, when farming communities expanded and forest burning was used for land clearance. In central Italy, this resulted in a 40-fold population decline. The overall genomic impact of this decline included the complete loss of variation in the mitochondrial genome and along long stretches of the nuclear genome. Several private and deleterious amino acid changes were fixed by random drift; predicted effects include energy deficit, muscle weakness, anomalies in cranial and skeletal development, and reduced aggressiveness. Despite this extreme loss of diversity, Apennine bear genomes show nonrandom peaks of high variation, possibly maintained by balancing selection, at genomic regions significantly enriched for genes associated with immune and olfactory systems. Challenging the paradigm of increased extinction risk in small populations, we suggest that random fixation of deleterious alleles (i) can be an important driver of divergence in isolation, (ii) can be tolerated when balancing selection prevents random loss of variation at important genes, and (iii) is followed by or results directly in favorable behavioral changes.