Load Of Deleterious Mutations Research Articles

Conservation genomics provides insights into genetic resilience and adaptation of the endangered Chinese hazelnut, Corylus chinensis

Global climate change has increased concerns regarding biodiversity loss. However, many key conservation issues still required further research, including demographic history, deleterious mutation load, adaptive evolution, and putative introgression. Here we generated the first chromosome-level genome of the endangered Chinese hazelnut, Corylus chinensis, and compared the genomic signatures with its sympatric widespread C. kwechowensis-C. yunnanensis complex. We found large genome rearrangements across all Corylus species and identified species-specific expanded gene families that may be involved in adaptation. Population genomics revealed that both C. chinensis and the C. kwechowensis-C. yunnanensis complex had diverged into two genetic lineages, forming a consistent pattern of southwestern-northern differentiation. Population size of the narrow southwestern lineages of both species have decreased continuously since the late Miocene, whereas the widespread northern lineages have remained stable (C. chinensis) or have even recovered from population bottlenecks (C. kwechowensis-C. yunnanensis complex) during the Quaternary. Compared with C. kwechowensis-C. yunnanensis complex, C. chinensis showed significantly lower genomic diversity and higher inbreeding level. However, C. chinensis carried significantly fewer deleterious mutations than C. kwechowensis-C. yunnanensis complex, as more effective purging selection reduced the accumulation of homozygous variants. We also detected signals of positive selection and adaptive introgression in different lineages, which facilitated the accumulation of favorable variants and formation of local adaptation. Hence, both types of selection and exogenous introgression could have mitigated inbreeding and facilitated survival and persistence of C. chinensis. Overall, our study provides critical insights into lineage differentiation, local adaptation, and the potential for future recovery of endangered trees.

Genome sequences and population genomics provide insights into the demographic history, inbreeding, and mutation load of two 'living fossil' tree species of Dipteronia.

'Living fossils', that is, ancient lineages of low taxonomic diversity, represent an exceptional evolutionary heritage, yet we know little about how demographic history and deleterious mutation load have affected their long-term survival and extinction risk. We performed whole-genome sequencing and population genomic analyses on Dipteronia sinensis and D. dyeriana, two East Asian Tertiary relict trees. We found large-scale genome reorganizations and identified species-specific genes under positive selection that are likely involved in adaptation. Our demographic analyses suggest that the wider-ranged D. sinensis repeatedly recovered from population bottlenecks over late Tertiary/Quaternary periods of adverse climate conditions, while the population size of the narrow-ranged D. dyeriana steadily decreased since the late Miocene, especially after the Last Glacial Maximum (LGM). We conclude that the efficient purging of deleterious mutations in D. sinensis facilitated its survival and repeated demographic recovery. By contrast, in D. dyeriana, increased genetic drift and reduced selection efficacy, due to recent severe population bottlenecks and a likely preponderance of vegetative propagation, resulted in fixation of strongly deleterious mutations, reduced fitness, and continuous population decline, with likely detrimental consequences for the species' future viability and adaptive potential. Overall, our findings highlight the significant impact of demographic history on levels of accumulation and purging of putatively deleterious mutations that likely determine the long-term survival and extinction risk of Tertiary relict trees.

Pleiotropic fitness effects across sexes and ages in the Drosophila genome and transcriptome.

Selection varies between categories of individuals, with far-reaching ramifications: Sex-specific selection can impede or accelerate adaptation, and differences in selection between young and old individuals are ultimately responsible for senescence. Here, we measure early- and late-life fitness in adults of both sexes from the Drosophila genetic reference panel and perform quantitative genetic and transcriptomic analyses. Fitness was heritable, showed positive pleiotropy across sexes and age classes, and appeared to be influenced by very large numbers of loci with small effects plus a smaller number with moderate effects. Most loci affected male and female fitness in the same direction; relatively few candidate sexually antagonistic loci were found, though these were enriched on the X chromosome as predicted by theory. The expression level of many genes showed an opposite correlation with fitness in males and females, consistent with unresolved sexual conflict over transcription. The load of deleterious mutations correlated negatively with fitness across genotypes, and we found some evidence for the mutation accumulation (but not the antagonistic pleiotropy) theory of aging.

Genomic signatures of bottleneck and founder effects in dingoes.

Dingoes arrived in Australia during the mid-Holocene and are the top-order terrestrial predator on the continent. Although dingoes subsequently spread across the continent, the initial founding population(s) could have been small. We investigated this hypothesis by sequencing the whole genomes of three dingoes and also obtaining the genome data from nine additional dingoes and 56 canines, including wolves, village dogs and breed dogs, and examined the signatures of bottlenecks and founder effects. We found that the nucleotide diversity of dingoes was low, 36% less than highly inbred breed dogs and 3.3 times lower than wolves. The number of runs of homozygosity (RoH) segments in dingoes was 1.6-4.7 times higher than in other canines. While examining deleterious mutational load, we observed that dingoes carried elevated ratios of nonsynonymous-to-synonymous diversities, significantly higher numbers of homozygous deleterious Single Nucleotide Variants (SNVs), and increased numbers of loss of function SNVs, compared to breed dogs, village dogs, and wolves. Our findings can be explained by bottlenecks and founder effects during the establishment of dingoes in mainland Australia. These findings highlight the need for conservation-based management of dingoes and the need for wildlife managers to be cognisant of these findings when considering the use of lethal control measures across the landscape.

The impact of habitat loss and population fragmentation on genomic erosion

Habitat loss and population fragmentation pose severe threats to biodiversity and the survival of many species. Population isolation and the decline in effective population size lead to increased genetic drift and inbreeding. In turn, this reduces neutral diversity, and it also affects the genetic load of deleterious mutations. Here, we analyse the effect of such genomic erosion by designing a spatially explicit, individual based model in SLiM, simulating the effects of the recorded habitat loss in Mauritius over the past ~ 250 years. We show that the loss of neutral diversity (genome-wide heterozygosity) was barely noticeable during the first 100 years of habitat loss. Changes to the genetic load took even more time to register, and they only became apparent circa 200 years after the start of habitat decline. Although a considerable number of deleterious mutations were lost by drift, others increased in frequency. The masked load was thus converted into a realised load, which compromised individual fitness and population viability after much of the native habitat had been lost. Importantly, genomic erosion continued after the metapopulation had stabilised at low numbers. Our study shows that historic habitat loss can pose a sustained threat to populations also in future generations, even without further habitat loss. The UN’s Decade on Ecosystem Restoration needs to lead to transformative change to save species from future extinction, and this requires the urgent restoration of natural habitats.

High-resolution mapping reveals the mechanism and contribution of genome insertions and deletions to RNA virus evolution

RNA viruses rapidly adapt to selective conditions due to the high intrinsic mutation rates of their RNA-dependent RNA polymerases (RdRps). Insertions and deletions (indels) in viral genomes are major contributors to both deleterious mutational load and evolutionary novelty, but remain understudied. To characterize the mechanistic details of their formation and evolutionary dynamics during infection, we developed a hybrid experimental-bioinformatic approach. This approach, called MultiMatch, extracts insertions and deletions from ultradeep sequencing experiments, including those occurring at extremely low frequencies, allowing us to map their genomic distribution and quantify the rates at which they occur. Mapping indel mutations in adapting poliovirus and dengue virus populations, we determine the rates of indel generation and identify mechanistic and functional constraints shaping indel diversity. Using poliovirus RdRp variants of distinct fidelity and genome recombination rates, we demonstrate tradeoffs between fidelity and Indel generation. Additionally, we show that maintaining translation frame and viral RNA structures constrain the Indel landscape and that, due to these significant fitness effects, Indels exert a significant deleterious load on adapting viral populations. Conversely, we uncover positively selected Indels that modulate RNA structure, generate protein variants, and produce defective interfering genomes in viral populations. Together, our analyses establish the kinetic and mechanistic tradeoffs between misincorporation, recombination, and Indel rates and reveal functional principles defining the central role of Indels in virus evolution, emergence, and the regulation of viral infection.

Multilevel selection in the evolution of sexual dimorphism in phenotypic plasticity.

Phenotypes are partly shaped by the environment, which can impact both short-term adaptation and long-term evolution. In dioecious species, the two sexes may exhibit different degrees of phenotypic plasticity and theoretical models indicate that such differences may confer an adaptive advantage when the population is subject to directional selection, either because of a systematically varying environment or a load of deleterious mutations. The effect stems from the fundamental asymmetry between the two sexes: female fertility is more limited than male fertility. Whether this asymmetry is sufficient for sexual dimorphism in phenotypic plasticity to evolve is, however, not obvious. Here, we show that even in conditions where it provides an adaptive advantage, dimorphic phenotypic plasticity may be evolutionarily unstable due to sexual selection. This is the case, in particular, for panmictic populations where mating partnerships are formed at random. However, we show that the effects of sexual selection can be counteracted when mating occurs within groups of related individuals. Under this condition, sexual dimorphism in phenotypic plasticity can not only evolve but offset the twofold cost of males. We demonstrate these points with a simple mathematical model through a combination of analytical and numerical results.

Deleterious mutation load in the admixed mice population

Deleterious mutation loads are known to correlate negatively with effective population size (Ne). Due to this reason, previous studies observed a higher proportion of harmful mutations in small populations than that in large populations. However, the mutational load in an admixed population that derived from introgression between individuals from two populations with vastly different Ne is not known. We investigated this using the whole genome data from two subspecies of the mouse (Mus musculus castaneus and Mus musculus musculus) with significantly different Ne. We used the ratio of diversities at nonsynonymous and synonymous sites (dN/dS) to measure the harmful mutation load. Our results showed that this ratio observed for the admixed population was intermediate between those of the parental populations. The dN/dS ratio of the hybrid population was significantly higher than that of M. m. castaneus but lower than that of M. m. musculus. Our analysis revealed a significant positive correlation between the proportion of M. m. musculus ancestry in admixed individuals and their dN/dS ratio. This suggests that the admixed individuals with high proportions of M. m. musculus ancestry have large dN/dS ratios. We also used the proportion of deleterious nonsynonymous SNVs as a proxy for deleterious mutation load, which also produced similar results. The observed results were in concordance with those expected by theory. We also show a shift in the distribution of fitness effects of nonsynonymous SNVs in the admixed genomes compared to the parental populations. These findings suggest that the deleterious mutation load of the admixed population is determined by the proportion of the ancestries of the subspecies. Therefore, it is important to consider the status and the level of genetic admixture of the populations whilst estimating the mutation loads.

The evolution of suppressed recombination between sex chromosomes and the lengths of evolutionary strata.

The idea that sex differences in selection drive the evolution of suppressed recombination between sex chromosomes is well developed in population genetics. Yet, despite a now classic body of theory, empirical evidence that sexually antagonistic selection drives the evolution of recombination arrest remains equivocal and alternative hypotheses underdeveloped. Here, we investigate whether the length of "evolutionary strata" formed by chromosomal inversions (or other large-effect recombination modifiers) expanding the non-recombining sex-linked region (SLR) on sex chromosomes can be informative of how selection influenced their fixation. We develop population genetic models to show how the length of an SLR-expanding inversion, and the presence of partially recessive deleterious mutational variation, affect the fixation probability of three different classes of inversions: (1) intrinsically neutral, (2) directly beneficial (i.e., due to breakpoint or positional effects), and (3) those capturing sexually antagonistic (SA) loci. Our models indicate that neutral inversions, and those capturing an SA locus in linkage disequilibrium with the ancestral SLR, will exhibit a strong fixation bias toward small inversions; while unconditionally beneficial inversions, and those capturing a genetically unlinked SA locus, will favor fixation of larger inversions. The footprint of evolutionary stratum size left behind by different selection regimes is strongly influenced by parameters affecting the deleterious mutation load, the physical position of the ancestral SLR, and the distribution of new inversion lengths.

Repeated turnovers keep sex chromosomes young in willows

BackgroundSalicaceae species have diverse sex determination systems and frequent sex chromosome turnovers. However, compared with poplars, the diversity of sex determination in willows is poorly understood, and little is known about the evolutionary forces driving their turnover. Here, we characterized the sex determination in two Salix species, S. chaenomeloides and S. arbutifolia, which have an XY system on chromosome 7 and 15, respectively.ResultsBased on the assemblies of their sex determination regions, we found that the sex determination mechanism of willows may have underlying similarities with poplars, both involving intact and/or partial homologs of a type A cytokinin response regulator (RR) gene. Comparative analyses suggested that at least two sex turnover events have occurred in Salix, one preserving the ancestral pattern of male heterogamety, and the other changing heterogametic sex from XY to ZW, which could be partly explained by the “deleterious mutation load” and “sexually antagonistic selection” theoretical models. We hypothesize that these repeated turnovers keep sex chromosomes of willow species in a perpetually young state, leading to limited degeneration.ConclusionsOur findings further improve the evolutionary trajectory of sex chromosomes in Salicaceae species, explore the evolutionary forces driving the repeated turnovers of their sex chromosomes, and provide a valuable reference for the study of sex chromosomes in other species.

Evolutionary models predict potential mechanisms of escape from mutational meltdown

Mutagenic drugs are promising candidates for the treatment of various RNA virus infections. Increasing the mutation rate of the virus leads to rapid accumulation of deleterious mutation load, which is proposed to ultimately result in extinction as described by the theoretical concepts of mutational meltdown and lethal mutagenesis. However, the conditions and potential mechanisms of viral escape from the effects of mutagenic drugs have not been conceptually explored. Here we apply a computational approach to quantify the population dynamics and genetics of a population under high mutation rates and discuss the likelihood of adaptation to a mutagenic drug by means of three proposed mechanisms: (1) a proportion of “traditional” beneficial mutations that increase growth/fitness, (2) a mutation rate modifier (i.e., evolution of resistance to the mutagenic drug) that reduces the mutation rate, and (3) a modifier of the distribution of fitness effects, which either decreases or increases deleterious effects of mutations (i.e., evolution of tolerance to the mutagenic drug). We track the population dynamics and genetics of evolving populations and find that successful adaptations have to appear early to override the increasing mutational load and rescue the population from its imminent extinction. We highlight that the observed stochasticity of adaptation, especially by means of modifiers of the distribution of fitness effects, is difficult to capture in experimental trials, which may leave potential dangers of the use of mutagenic treatments unexposed.

Sexual selection for males with beneficial mutations

Sexual selection is the process by which traits providing a mating advantage are favoured. Theoretical treatments of the evolution of sex by sexual selection propose that it operates by reducing the load of deleterious mutations. Here, we postulate instead that sexual selection primarily acts through females preferentially mating with males carrying beneficial mutations. We used simulation and analytical modelling to investigate the evolutionary dynamics of beneficial mutations in the presence of sexual selection. We found that female choice for males with beneficial mutations had a much greater impact on genetic quality than choice for males with low mutational load. We also relaxed the typical assumption of a fixed mutation rate. For deleterious mutations, mutation rate should always be minimized, but when rare beneficial mutations can occur, female choice for males with those rare beneficial mutations could overcome a decline in average fitness and allow an increase in mutation rate. We propose that sexual selection for beneficial mutations could overcome the ‘two-fold cost of sex’ much more readily than choice for males with low mutational load and may therefore be a more powerful explanation for the prevalence of sexual reproduction than the existing theory. If sexual selection results in higher fitness at higher mutation rates, and if the variability produced by mutation itself promotes sexual selection, then a feedback loop between these two factors could have had a decisive role in driving adaptation.

Mutational load and deleterious mutations in goat genome from Kenya

Different domestication processes such as selection and effective population size are among other factors responsible for the accumulation of mutations in an animal. This study investigated the mutation load and accumulation of deleterious mutations in Kenyan goat populations using Single Nucleotide Polymorphism (SNP) data obtained from local (Galla = 12) and exotic (Saanen = 24, Alpine = 28, and Toggenburg = 30) goat genotypes. The SNP annotation was done on the ENSEMBLE goat (Capra hircus) using the Variant Effect Predictor (VEP). Sorting Intolerant from Tolerant (SIFT) was done on the annotated file using a score of > 0.01 to describe highly deleterious mutations. Biomart tool in the ENSEMBL goat C. hircus was used for Gene Ontology (GO) for the genes identified from highly deleterious mutations. The analysis disclosed no differences in mutation load among the studied genotypes. Overall, the synonymous mutations were in abundance compared to missense mutations, totaling 693 and 258 representing 1.01% and 0.37%, respectively. The calculated mutation load was similar (0.37) suggesting exposure of goats to similar domestication processes that are creating similar effects on the animal’s genome. Further analysis of the missense variants revealed 126 deleterious mutations and 132 tolerated mutations. A total of 111 genes were identified from the deleterious mutations and only 5 were among the highly deleterious mutations (SIFT score > 0.01) which include PROS1, EHBP1, LTN1, LRRN4, and FNDC3A. Gene Ontology describes these genes as responsible for different functions associated with animal reproduction, diseases, and memory. This study's results have confirmed the levels of mutation load and the presence of deleterious mutations in Kenyan goats. This can be used as a base to predict the future rate of mutation load to ensure better implementation of conservation programs to avoid an accumulation of deleterious mutations.

Prediction of fitness under different breeding designs in conservation programs

AbstractThe expected change in fitness under inbreeding due to deleterious recessive alleles depends on the amount of inbreeding load harbored by a population, that is, the load of deleterious recessive mutations concealed in the heterozygous state, and the opposing effect of genetic purging to remove such a load. This change in fitness can be thus predicted if an estimate of the inbreeding load and the purging coefficient (the parameter that quantifies the amount of purging) are available. These two parameters can be estimated in pedigreed populations, as has been shown for populations under random mating. A question arises whether these parameters can also be estimated under other breeding systems as well as whether they allow accurate prediction of the corresponding expected change in fitness. In conservation programs, it is usually recommended to preserve genetic diversity by equalizing contributions from parents to progeny and avoiding inbred matings. Regular systems of inbreeding have also been proposed as breeding conservation strategies to purge the inbreeding load. Using computer simulations, we first test a method to jointly estimate the initial inbreeding load and the purging coefficient in populations subjected to equalization of parental contributions, circular mating, and partial full‐sib mating. Then, using the expected values of the inbreeding coefficient and the variance of family size, as well as the estimates of the inbreeding load and the purging coefficient, we make simple predictions of the change in fitness over generations under these breeding systems and compare them with simulation results. We discuss how these fitness predictions can help undertaking conservation designs under different breeding scenarios.

No evidence for temporally balanced selection on larval Pacific oysters Crassostrea gigas: a comment on Durland et al. (2021).

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Hedgecock Dennis 2022No evidence for temporally balanced selection on larval Pacific oysters Crassostrea gigas: a comment on Durland et al. (2021)Proc. R. Soc. B.2892021257920212579http://doi.org/10.1098/rspb.2021.2579SectionYou have accessCommentNo evidence for temporally balanced selection on larval Pacific oysters Crassostrea gigas: a comment on Durland et al. (2021) Dennis Hedgecock Dennis Hedgecock http://orcid.org/0000-0002-3995-646X Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-0371, USA [email protected] Google Scholar Find this author on PubMed Search for more papers by this author Dennis Hedgecock Dennis Hedgecock http://orcid.org/0000-0002-3995-646X Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-0371, USA [email protected] Google Scholar Find this author on PubMed Search for more papers by this author Published:01 June 2022https://doi.org/10.1098/rspb.2021.2579This article comments on the following:Research ArticleTemporally balanced selection during development of larval Pacific oysters (Crassostrea gigas) inherently preserves genetic diversity within offspringhttps://doi.org/10.1098/rspb.2020.3223 Evan Durland, Pierre De Wit and Chris Langdon volume 288issue 1958Proceedings of the Royal Society B: Biological Sciences01 September 2021 Review history Review history is available via Web of Science at https://www.webofscience.com/api/gateway/wos/peer-review/10.1098/rspb.2021.2579/ Durland et al. [1] claim that temporally balanced selection preserves genetic diversity in a developing larval cohort of Pacific oysters produced from wild-caught parents. Their assertion is based upon pooled DNA sequencing estimates of changes in SNP minor-allele frequencies (MAFs) in the cohort. Finding bidirectional changes in allele frequencies for 17% of markers—allele-frequency change is detected at 473 of 751 markers; of these, 127 show bidirectional changes over the course of 22 days of development—they conclude that ‘temporal patterns of changes in allele frequencies for a significant proportion of loci are inconsistent with simple explanations of directional selection and purging of deleterious mutations’. Durland et al.'s null hypothesis that purifying selection ought only to produce unidirectional changes in MAF is ill-informed, divorced from classical mutational load theory [2], and at odds with abundant empirical evidence concerning large genetic loads in the Pacific oyster and other bivalve molluscs.Frequencies of marker genotypes change within bivalve families because of viability selection against linked deleterious mutations (Plough [3] reviews nearly a half-century of research on this topic), but in a mixed cohort of families, the magnitude and direction of allele-frequency changes are necessarily conditioned on the complex genetic architectures (i.e. linkage of markers and mutations, strength of selection and degree of dominance) and temporal patterns of genotype-dependent viability selection within each family [4–10]. Two simple examples suffice to illustrate that trajectories of SNP MAFs in a mixed cohort of families with different genetic architectures need not be unidirectional (table 1). One reason not to expect simple directional changes in MAF is that a deleterious mutation (mapped as a quantitative-trait locus affecting viability or a vQTL [7,9,10]) may be linked either to the minor allele or to its alternative in different families, leading possibly to offsetting changes in MAF (table 1a). Another reason not to expect a simple directional change in MAF is that different vQTL may be expressed at different stages of larval development [7], leading potentially to bidirectional changes in MAF (table 1b). Simply put, the nature of genotype-dependent selection within families cannot be inferred from observing MAF changes in a pool of those families. Durland et al.'s data are compatible with the paradigm of purifying selection, which has been established by direct observations of genotype-dependent survival within families [3–10]. Durland et al.'s additional expectation that purifying selection should have eliminated some SNP alleles is unreasonable, since partially dominant, deleterious mutations in random-bred families would be carried in heterozygotes, which have average fitness of 0.5–0.7 relative to wild-type homozygotes [9,10] and would not be eliminated within a single generation. Table 1. Examples of MAFs in pools of two families with different SNP-vQTL architectures.a Collapse family 1vQTL in family 1family 2vQTL in family 2MAF in poolcross: a*A//bB × bC//bDACADBCBDcross: aA//b*B × bC//bDACADBCBDdayf[a](a) selection at day 10 against haplotype a*-A in family 1 and against haplotype b*-B in family 2frequency at fertilization0.250.250.250.250.250.250.250.2500.25fitness day 100.50.511110.50.5frequency at day 120.1670.1670.3330.3330.3330.3330.1670.167120.25(b) selection at day 10 against haplotype a*-A in family 1; selection at day 20 against haplotype b*-B in family 2frequency at fertilization0.250.250.250.250.250.250.250.2500.25fitness day 100.50.5111111frequency at day 120.1670.1670.3330.3330.250.250.250.25120.21fitness day 201111110.3330.333frequency at day 220.1670.1670.3330.3330.3750.3750.1250.125220.26aSNP alleles denoted by lowercase letters; a, minor allele; asterisk denotes tight linkage to deleterious mutation at vQTL. Alleles at vQTL are A, B (paternal) and C, D (maternal). Fitness values modelled after [7,8]. Pools start out 1 : 1, but the ratio changes, following selective mortality; allele frequencies in pool are weighted by family survival proportions.Durland et al. produced a larval cohort by a factorial cross of 5 males × 19 females, pooling families in approximately equal proportions 1 h after fertilization. Substantial research has repeatedly shown that mass or pooled spawns of bivalves result in progressively uneven representations of families through larval development, owing to a high variance in reproductive success [11–21]. This variance in reproductive success arises from variation in gamete quality, sperm-egg interactions and larval mortality and has non-genetic [22] and genetic components [11,23]. Often, over the course of larval development, there is a complete loss of half-sib families (rows or columns in a factorial mating design), even though fertilization is initially apparently successful [11,24,25]. Such variance in reproductive success reduces the effective size of a cohort, by 30% or more from the actual number of parents [11,15]. Thus, of the 24 parents used by Durland et al., far fewer were likely represented in the cohort by the end of larval development. Parental contributions and the relative abundances of families, moreover, are only weakly correlated or are uncorrelated from one time point to another during larval development [15,16,18]. Thus, SNP-allele frequencies are expected to change markedly and in different directions in pools of families over time, not because of changing selection pressures on SNP alleles, as claimed by Durland et al., but because of shifting family composition in the cohort.Finally, Durland et al. estimate SNP-allele frequencies from fertilized egg and larval DNA pools, but this approach assumes that individuals in a sample provide a similar number of DNA templates, which is doubtful. For example, because polar bodies remain adhered to fertilized eggs [26], the ratio of female to male DNA in a pool of eggs collected at 1 h post-fertilization is 4 : 1. Later, during development, individual larvae, even full-sibs, become progressively heterogeneous in size and mass; by day 10, for example, ash-free dry organic mass of the largest larva in a family can be 5× that of its smallest sibling and the average dry organic mass of larvae in a fast-growing family may be 2× that of larvae in a slow-growing family (calculated, for example, from data in [27], using the dry organic mass-to-length regression in [28]; cell numbers and DNA content are directly proportional to biochemical composition in marine invertebrate larvae [29]). That families can have very different average sizes is also demonstrated by the very different proportions of families in a size-graded mixed cohort compared to its non-graded control [16]. Thus, Durland et al.'s estimates of SNP-allele frequencies in pooled samples are biased, likely, by differences in template abundance, violating a basic assumption of DNA-pooling methods [30].Durland et al.'s inference of temporally balanced selection acting on larval Pacific oysters is based on fundamental conceptual and methodological errors. Their observations are compatible with and more readily explained by a large load of deleterious mutations affecting the survival of early life stages and by variance in the reproductive success of pooled, hatchery-propagated families. The hypothesis that temporally balanced selection preserves genetic diversity within larval cohorts is neither warranted nor necessary.Pooled DNA-sequencing approaches have been used in several recent studies of genetic change in larval cohorts of bivalves and other marine invertebrates (e.g. [31–33]). While a detailed critique of these works is beyond the scope of this comment, the caveats expressed here about pooling of samples may apply to them as well. Pooled DNA-sequencing in experiments is facile and possibly suited to answering some biological questions, but understanding genotype-dependent selection is still probably best achieved by applying the tried-and-true methods of Mendelian experimental genetics (i.e. analyses of individual progeny from single-pair crosses or assignment of individual progeny to parents if families must be pooled, coupled with QTL-mapping methods to identify genomic foci and modes of selection).Data accessibilityThis article has no additional data.Authors' contributionsD.H.: conceptualization, writing—original draft and writing—review and editing.Competing interestsI declare I have no competing interests.FundingI received no funding for this study.AcknowledgementsThe author thanks Drs Louis V. Plough, Xiaoshen Yin and especially Donal T. Manahan for reading and commenting on this note. He is grateful, as well, for the support provided to the Paxson H. Offield Professor in Fisheries Ecology.FootnotesThe accompanying reply can be viewed at http://dx.doi.org/10.1098/rspb.2022.0197.© 2022 The Author(s)Published by the Royal Society. All rights reserved.

Demographic History and Natural Selection Shape Patterns of Deleterious Mutation Load and Barriers to Introgression across Populus Genome

Hybridization and resulting introgression are important processes shaping the tree of life and appear to be far more common than previously thought. However, how the genome evolution was shaped by various genetic and evolutionary forces after hybridization remains unresolved. Here we used whole-genome resequencing data of 227 individuals from multiple widespread Populus species to characterize their contemporary patterns of hybridization and to quantify genomic signatures of past introgression. We observe a high frequency of contemporary hybridization and confirm that multiple previously ambiguous species are in fact F1 hybrids. Seven species were identified, which experienced different demographic histories that resulted in strikingly varied efficacy of selection and burdens of deleterious mutations. Frequent past introgression has been found to be a pervasive feature throughout the speciation of these Populus species. The retained introgressed regions, more generally, tend to contain reduced genetic load and to be located in regions of high recombination. We also find that in pairs of species with substantial differences in effective population size, introgressed regions are inferred to have undergone selective sweeps at greater than expected frequencies in the species with lower effective population size, suggesting that introgression likely have higher potential to provide beneficial variation for species with small populations. Our results, therefore, illustrate that demography and recombination have interplayed with both positive and negative selection in determining the genomic evolution after hybridization.

Distinctive mitogenomic lineages within populations of White-tailed Eagles

Abstract Using whole mitochondrial DNA sequences from 89 White-tailed Eagles (Haliaeetus albicilla) sampled from Iceland, Greenland, Norway, Denmark and Estonia between 1990 and 2018, we investigate the mitogenomic variation within and between countries. We show that there is a substantial population differentiation between the countries, reflecting similar major phylogeographic patterns obtained previously for the control region of the mitochondria, which suggested two main refugia during the last glacial period. Distinct mitogenomic lineages are observed within countries with divergence times exceeding the end of the last glacial period of the Ice Age. Deviations from neutrality indicate that these lineages have been maintained by natural selection and there is an excess of segregating amino acids in comparison with number of fixations suggesting a large load of deleterious mutations. The maintenance of the distinct mitogenic lineages within countries inflates our estimates of divergence times.

Demographic history and identification of threats revealed by population genomic analysis provide insights into conservation for an endangered maple.

Recent advancements in whole genome sequencing techniques capable of covering nearly all the nucleotide variations of a genome would make it possible to set up a conservation framework for threatened plants at the genomic level. Here we applied a whole genome resequencing approach to obtain genome-wide data from 105 individuals sampled from the 10 currently known extant populations of Acer yangbiense, an endangered species with fragmented habitats and restricted distribution in Yunnan, China. To inform meaningful conservation action, we investigated what factors might have contributed to the formation of its extremely small population sizes and what threats it currently suffers at a genomic level. Our results revealed that A.yangbiense has low genetic diversity and comprises different numbers of genetic groups based on neutral (seven) and selected loci (13), with frequent gene flow between populations. Repeated bottleneck events, particularly the most recent one occurring within ~10,000years before present, which decreased its effective population size (Ne )<200, and severe habitat fragmentation resulting from anthropogenic activities as well as a biased gender ratio of mature individuals in its natural habitat, might have together contributed to the currently fragmented and endangered status of A.yangbiense. The species has suffered from inbreeding and deleterious mutation load, both of which varied among populations but had similar patterns; that is, populations with higher FROH (frequency of runs of homozygosity) always carried a larger number of deleterious mutations in the homozygous state than in populations with lower FROH. In addition, based on our genetic differentiation results, and the distribution patterns of homozygous deleterious mutations in individuals, we recommend certain conservation actions regarding the genetic rescue of A.yangbiense. Overall, our study provides meaningful insights into the conservation genetics and a framework for the further conservation for the endangered A.yangbiense.

Relaxation of purifying selection suggests low effective population size in eusocial Hymenoptera and solitary pollinating bees

With one of the highest number of parasite, eusocial and pollinator species among all insect orders, Hymenoptera features a great diversity of specific lifestyles. At the population genetic level, such life-history strategies are expected to decrease effective population size and efficiency of purifying selection. In this study, we tested this hypothesis by estimating the relative rate of non-synonymous substitution in 169 species to investigate the variation in natural selection efficiency throughout the hymenopteran tree of life. We found no effect of parasitism or body size, but show that relaxed selection is associated with eusociality, suggesting that the division of reproductive labour decreases effective population size in ants, bees and wasps. Unexpectedly, the effect of eusociality is marginal compared to a striking and widespread relaxation of selection in both social and non social bees, which indicates that these keystone pollinator species generally feature low effective population sizes. This widespread pattern suggests specific constraints in pollinating bees potentially linked to limited resource and high parental investment. The particularly high load of deleterious mutations we report in the genome of these crucial ecosystem engineer species also raises new concerns about their ongoing population decline.

Genetic load has potential in large populations but is realized in small inbred populations.

Populations with higher genetic diversity and larger effective sizes have greater evolutionary capacity (i.e., adaptive potential) to respond to ecological stressors. We are interested in how the variation captured in protein‐coding genes fluctuates relative to overall genomic diversity and whether smaller populations suffer greater costs due to their genetic load of deleterious mutations compared with larger populations. We analyzed individual whole‐genome sequences (N = 74) from three different populations of Montezuma quail (Cyrtonyx montezumae), a small ground‐dwelling bird that is sustainably harvested in some portions of its range but is of conservation concern elsewhere. Our historical demographic results indicate that Montezuma quail populations in the United States exhibit low levels of genomic diversity due in large part to long‐term declines in effective population sizes over nearly a million years. The smaller and more isolated Texas population is significantly more inbred than the large Arizona and the intermediate‐sized New Mexico populations we surveyed. The Texas gene pool has a significantly smaller proportion of strongly deleterious variants segregating in the population compared with the larger Arizona gene pool. Our results demonstrate that even in small populations, highly deleterious mutations are effectively purged and/or lost due to drift. However, we find that in small populations the realized genetic load is elevated because of inbreeding coupled with a higher frequency of slightly deleterious mutations that are manifested in homozygotes. Overall, our study illustrates how population genomics can be used to proactively assess both neutral and functional aspects of contemporary genetic diversity in a conservation framework while simultaneously considering deeper demographic histories.