RESUMO
The long-term balancing selection acting on mating types or sex-determining genes is expected to lead to the accumulation of deleterious mutations in the tightly linked chromosomal segments that are locally 'sheltered' from purifying selection. However, the factors determining the extent of this accumulation are poorly understood. Here, we took advantage of variations in the intensity of balancing selection along a dominance hierarchy formed by alleles at the sporophytic self-incompatibility system of the Brassicaceae to compare the pace at which linked deleterious mutations accumulate among them. We first experimentally measured the phenotypic manifestation of the linked load at three different levels of the dominance hierarchy. We then sequenced and phased polymorphisms in the chromosomal regions linked to 126 distinct copies of S-alleles in two populations of Arabidopsis halleri and three populations of Arabidopsis lyrata. We find that linkage to the S-locus locally distorts phylogenies over about 10-30 kb along the chromosome. The more intense balancing selection on dominant S-alleles results in greater fixation of linked deleterious mutations, while recessive S-alleles accumulate more linked deleterious mutations that are segregating. Hence, the structure rather than the overall magnitude of the linked genetic load differs between dominant and recessive S-alleles. Our results have consequences for the long-term evolution of new S-alleles, the evolution of dominance modifiers between them, and raise the question of why the non-recombining regions of some sex and mating type chromosomes expand over evolutionary times while others, such as the S-locus of the Brassicaceae, remain restricted to small chromosomal regions.
Assuntos
Alelos , Arabidopsis , Arabidopsis/genética , Seleção Genética , Autoincompatibilidade em Angiospermas/genética , Carga Genética , Mutação , Genes Dominantes , FenótipoRESUMO
Dominance is a fundamental parameter in genetics, determining the dynamics of natural selection on deleterious and beneficial mutations, the patterns of genetic variation in natural populations, and the severity of inbreeding depression in a population. Despite this importance, dominance parameters remain poorly known, particularly in humans or other non-model organisms. A key reason for this lack of information about dominance is that it is extremely challenging to disentangle the selection coefficient (s) of a mutation from its dominance coefficient (h). Here, we explore dominance and selection parameters in humans by fitting models to the site frequency spectrum (SFS) for nonsynonymous mutations. When assuming a single dominance coefficient for all nonsynonymous mutations, we find that numerous h values can fit the data, so long as h is greater than ~0.15. Moreover, we also observe that theoretically-predicted models with a negative relationship between h and s can also fit the data well, including models with h = 0.05 for strongly deleterious mutations. Finally, we use our estimated dominance and selection parameters to inform simulations revisiting the question of whether the out-of-Africa bottleneck has led to differences in genetic load between African and non-African human populations. These simulations suggest that the relative burden of genetic load in non-African populations depends on the dominance model assumed, with slight increases for more weakly recessive models and slight decreases shown for more strongly recessive models. Moreover, these results also demonstrate that models of partially recessive nonsynonymous mutations can explain the observed severity of inbreeding depression in humans, bridging the gap between molecular population genetics and direct measures of fitness in humans. Our work represents a comprehensive assessment of dominance and deleterious variation in humans, with implications for parameterizing models of deleterious variation in humans and other mammalian species.
Assuntos
Genética Populacional , Genoma Humano , Modelos Genéticos , Mutação , Seleção Genética , Humanos , Seleção Genética/genética , Genes Dominantes , Variação Genética , Carga Genética , Depressão por Endogamia/genéticaRESUMO
Current rates of habitat degradation and climate change are causing unprecedented declines in global biodiversity. Studies on vertebrates highlight how conservation genomics can be effective in identifying and managing threatened populations, but it is unclear how vertebrate-derived metrics of genomic erosion translate to invertebrates, with their markedly different population sizes and life histories. The Black-veined White butterfly (Aporia crataegi) was extirpated from Britain in the 1920s. Here, we sequenced historical DNA from 17 specimens collected between 1854 and 1924 to reconstruct demography and compare levels of genomic erosion between extirpated British and extant European mainland populations. We contrast these results using modern samples of the Common Blue butterfly (Polyommatus icarus); a species with relatively stable demographic trends in Great Britain. We provide evidence for bottlenecks in both these species around the period of post-glacial colonization of the British Isles. Our results reveal different demographic histories and Ne for both species, consistent with their fates in Britain, likely driven by differences in life history, ecology and genome size. Despite a difference, by an order of magnitude, in historical effective population sizes (Ne), reduction in genome-wide heterozygosity in A. crataegi was comparable to that in P. icarus. Symptomatic of A. crataegi's disappearance were marked increases in runs-of-homozygosity (RoH), potentially indicative of recent inbreeding, and accumulation of putatively mildly and weakly deleterious variants. Our results provide a rare glimpse of genomic erosion in a regionally extinct insect and support the potential use of genomic erosion metrics in identifying invertebrate populations or species in decline.
Assuntos
Borboletas , Evolução Molecular , Animais , Borboletas/genética , Europa (Continente) , Extinção Biológica , Carga Genética , Variação Genética , Endogamia , Perda de Heterozigosidade , Dinâmica Populacional , Reino UnidoRESUMO
The Chinese pangolin (Manis pentadactyla, MP) has been extensively exploited and is now on the brink of extinction, but its population structure, evolutionary history, and adaptive potential are unclear. Here, we analyzed 94 genomes from three subspecies of the Chinese pangolin and identified three distinct genetic clusters (MPA, MPB, and MPC), with MPB further divided into MPB1 and MPB2 subpopulations. The divergence of these populations was driven by past climate change. For MPB2 and MPC, recent human activities have caused dramatic population decline and small population size as well as increased inbreeding, but not decrease in genomic variation and increase in genetic load probably due to strong gene flow; therefore, it is crucial to strengthen in situ habitat management for these two populations. By contrast, although human activities have a milder impact on MPA, it is at high risk of extinction due to long-term contraction and isolation, and genetic rescue is urgently needed. MPB1 exhibited a relatively healthy population status and can potentially serve as a source population. Overall, our findings provide novel insights into the conservation of the Chinese pangolin and biogeography of the mammals of eastern Asia.
Assuntos
Pangolins , Pangolins/genética , Animais , Genômica , Atividades Humanas , Humanos , Espécies em Perigo de Extinção , Evolução Biológica , Mudança Climática , Carga Genética , Cruzamento , Genética Populacional , ÁsiaRESUMO
The future survival of coral reefs in the Anthropocene depends on the capacity of corals to adapt as oceans warm and extreme weather events become more frequent. Targeted interventions designed to assist evolutionary processes in corals require a comprehensive understanding of the distribution and structure of standing variation, however, efforts to map genomic variation in corals have so far focussed almost exclusively on SNPs, overlooking structural variants that have been shown to drive adaptive processes in other taxa. Here, we show that the reef-building coral, Acropora kenti, harbours at least five large, highly polymorphic structural variants, all of which exhibit signatures of strongly suppressed recombination in heterokaryotypes, a feature commonly associated with chromosomal inversions. Based on their high minor allele frequency, uniform distribution across habitats and elevated genetic load, we propose that these inversions in A. kenti are likely to be under balancing selection. An excess of SNPs with high impact on protein-coding genes within these loci elevates their importance both as potential targets for adaptive selection and as contributors to genetic decline if coral populations become fragmented or inbred in future.
Assuntos
Antozoários , Inversão Cromossômica , Recifes de Corais , Polimorfismo de Nucleotídeo Único , Antozoários/genética , Inversão Cromossômica/genética , Animais , Polimorfismo de Nucleotídeo Único/genética , Seleção Genética , Frequência do Gene , Carga Genética , Mutação , Genética PopulacionalRESUMO
The 22q11.2 deletion syndrome (22q11.2DS) is associated with high psychiatric morbidity. However, large phenotypic heterogeneity hampers early detection of 22q11.2DS individuals at highest risk. Here, we investigated whether individuals with 22q11.2DS can be subdivided into clinically relevant subgroups based on their severity of cognitive impairments and whether such subgroups differ in polygenic risk. Using a cross-sectional design, we examined the number of lifetime psychiatric diagnoses and polygenic risk scores for schizophrenia in an unselected nationwide biobank cohort of individuals with 22q11.2DS (n = 183). Approximately 35% of this sample, aged 10-30 years, had a history with one or more psychiatric diagnosis. In a representative nested subgroup of 28 children and youth, we performed additional comprehensive cognitive evaluation and assessed psychiatric symptoms. Unsupervised hierarchical cluster analysis was performed to divide the subgroup of 22q11.2DS individuals, based on their performance on the cognitive testing battery. This produced two groups that did not differ in mean age or gender composition, but were characterized by low cognitive (LF) and high cognitive (HF) functional levels. The LF group, which had significantly lower global cognitive functioning scores, also displayed higher negative symptom scores; whereas, the HF group displayed lower rate of current psychiatric disorders than the LF group and the reminder of the biobank cohort. The polygenic risk score for schizophrenia was insignificantly lower for the low functioning group than for the high functioning group, after adjustment. Cognitive functioning may provide useful information on psychiatric risk.
Assuntos
Disfunção Cognitiva , Síndrome de DiGeorge , Humanos , Síndrome de DiGeorge/complicações , Síndrome de DiGeorge/fisiopatologia , Feminino , Masculino , Adolescente , Criança , Adulto , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Adulto Jovem , Estudos Transversais , Carga Genética , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Herança MultifatorialRESUMO
Zoo populations of threatened species are a valuable resource for the restoration of wild populations. However, their small effective population size poses a risk to long-term viability, especially in species with high genetic load. Recent bioinformatic developments can identify harmful genetic variants in genome data. Here, we advance this approach, analysing the genetic load in the threatened pink pigeon (Nesoenas mayeri). We lifted the mutation-impact scores that had been calculated for the chicken (Gallus gallus) to estimate the genetic load in six pink pigeons. Additionally, we perform in silico crossings to predict the genetic load and realized load of potential offspring. We thus identify the optimal mate pairs that are theoretically expected to produce offspring with the least inbreeding depression. We use computer simulations to show how genomics-informed conservation can reduce the genetic load whilst reducing the loss of genome-wide diversity. Genomics-informed management is likely to become instrumental in maintaining the long-term viability of zoo populations.
Assuntos
Cruzamento , Columbidae , Columbidae/genética , Columbidae/fisiologia , Animais , Animais de Zoológico , Carga Genética , Cruzamento/métodos , Genômica , Conservação dos Recursos Naturais , Simulação por Computador , Depressão por EndogamiaRESUMO
High intra-specific genetic diversity is associated with adaptive potential, which is key for resilience to global change. However, high variation may also support deleterious alleles through genetic load, thereby increasing the risk of inbreeding depression if population sizes decrease. Purging of deleterious variation has been demonstrated in some threatened species. However, less is known about the costs of declines and inbreeding in species with large population sizes and high genetic diversity even though this encompasses many species globally that are expected to undergo population declines. Caribou is a species of ecological and cultural significance in North America with a wide distribution supporting extensive phenotypic variation but with some populations undergoing significant declines resulting in their at-risk status in Canada. We assessed intra-specific genetic variation, adaptive divergence, inbreeding, and genetic load across populations with different demographic histories using an annotated chromosome-scale reference genome and 66 whole-genome sequences. We found high genetic diversity and nine phylogenomic lineages across the continent with adaptive diversification of genes, but also high genetic load among lineages. We found highly divergent levels of inbreeding across individuals, including the loss of alleles by drift but not increased purging in inbred individuals, which had more homozygous deleterious alleles. We also found comparable frequencies of homozygous deleterious alleles between lineages regardless of nucleotide diversity. Thus, further inbreeding may need to be mitigated through conservation efforts. Our results highlight the "double-edged sword" of genetic diversity that may be representative of other species atrisk affected by anthropogenic activities.
Assuntos
Genética Populacional , Rena , Humanos , Animais , Carga Genética , Endogamia , Dinâmica Populacional , Variação GenéticaRESUMO
While haplotype-specific genetic load shapes the evolutionary trajectory of natural and captive populations, mixed-haplotype assembly and genotyping hindered its characterization in diploids. Herein, we produced two phased genome assemblies of the critically endangered fish Chinese Bahaba (Bahaba taipingensis, Sciaenidae, Teleostei) and resequenced 20 whole genomes to quantify population genetic load at a haplotype level. We identified frame-shifting variants as the most deleterious type, followed by mutations in the 5'-UTR, 3'-UTR and missense mutations at conserved amino acids. Phased haplotypes revealed gene deletions and high-impact deleterious variants. We estimated ~1.12% of genes missing or interrupted per haplotype, with a significant overlap of disrupted genes (30.35%) between haplotype sets. Relative proportions of deleterious variant categories differed significantly between haplotypes. Simulations suggested that purifying selection struggled to purge slightly deleterious genetic load in captive breeding compared to genotyping interventions, and that higher inter-haplotypic variance of genetic load predicted more efficient purging by artificial selection. Combining the knowledge of haplotype-resolved genetic load with predictive modelling will be immensely useful for understanding the evolution of deleterious variants and guiding conservation planning.
Assuntos
Variação Genética , Perciformes , Animais , Haplótipos/genética , Carga Genética , Mutação , Perciformes/genética , ChinaRESUMO
The genetic load hypothesis of Hermann Muller raised the profound question of possible species extinction, even for humans, following a prolonged accumulation of recessive genes due to ionizing radiation exposure within the population. Two major mouse radiation research teams in the United States provided the most extensive tests of Muller's hypothesis. One group continued its study for more than two decades, over 82 consecutive generations, approximating 2500 human years. Even though Muller had stressed for decades his fear of species-threatening effects, no significant effects were observed for related factors such as reproductive fitness and longevity. Yet, the paper presenting the data of the 82-generation negative study has only been cited five times in 45 years. Altogether numerous laboratories worldwide collected vast amounts of data on mice, rats, and swine in an unsuccessful attempt to see if there was convincing evidence to support the genetic load theory and claims that species might deteriorate or be rendered extinct. This paper re-examines Muller's genetic load hypothesis with a new evaluation of how that hypothesis was tested and the significance of the findings, with most of those studies being completed before the BEIR I Committee Report in 1972. That committee briefly discussed the available evidence, mostly ignoring those results as they proceeded to make hereditary risk estimates both for (1) the first generation after a radiation exposure and (2) for the time, in the distant future, when a hypothetical genetic equilibrium would be reached. Their estimates assumed accumulation of harmful mutations and a linear no-threshold dose response extending all of the way down to a single ionization. More recent data on induction by ionizing radiation of dominant mutations that affect the skeletons of mice provide further robust supporting evidence that the generationally cumulative and LNT-based assumptions underpinning Muller's genetic load hypothesis are not correct.
Assuntos
Extinção Biológica , Exposição à Radiação , Humanos , Animais , Camundongos , Ratos , Suínos , Carga Genética , Mutação , Radiação IonizanteRESUMO
Sintomas de ansiedade e depressão na infância têm sido amplamente investigados na atualidade. Os estudos apontam que esses sintomas têm natureza multifatorial, sendo os fatores ambientais, como as caraterísticas do funcionamento familiar, alvo de atenção dos pesquisadores. Por isso, este estudo avaliou a correlação e o poder preditivo dos fatores da parentalidade e da coparentalidade em sintomas clínicos de ansiedade e depressão nos filhos. Os participantes, 50 indivíduos que vivem em coabitação com o parceiro e têm pelo menos um filho com idade entre 7 e 11 anos, preencheram um instrumento composto por seis escalas, que avaliaram a parentalidade, a coparentalidade e a sintomatologia na prole. Os resultados indicaram correlações baixas e moderadas entre os fatores da parentalidade e da coparentalidade e os sintomas emocionais e comportamentais dos filhos. O conflito familiar coparental e a supervisão do comportamento foram preditores de 16% dos sintomas de ansiedade generalizada na prole e a triangulação familiar de 17% dos sintomas de depressão. Evidencia-se, como indica a literatura, que os filhos são suscetíveis à qualidade do funcionamento dos subsistemas parental e coparental.(AU)
Anxiety and depression symptoms in the early childhood have been investigated extensively in current times. Studies have point out that these symptoms have a multifactorial nature, with environment factors, such as the characteristics of the familiar functioning, as the researchers' target. Therefore, this study evaluated the correlation and the predictive power of parenting and co-parenting factors on clinical symptoms of anxiety and depression in the children. The participants, 50 individuals who lived in cohabitation with their partners and that had at least one child aged between 7 and 11 years old, filled in a form composed of six scales; which evaluated the parenting, the coparenting, and the offspring symptomatology. The results revealed low and moderate correlations between the parenting and coparenting variables and the emotional and behavioral symptoms of the children. The coparental familiar conflict and the behavior monitoring were predictors of 16% of the generalized anxiety symptom in the offspring, and the familiar triangulation of 17% of the depression symptoms. It shows, as the literature suggests, that the children are vulnerable to the quality of the functioning of the parental and coparental subsystems.(AU)
Los síntomas de ansiedad y depresión en la infancia son ampliamente investigados en la actualidad. Los estudios demuestran que los síntomas son multifactoriales, de los cuales los factores ambientales y las características de funcionamiento de la familia están en el centro de la atención de los investigadores. Por lo tanto, este estudio evaluó la correlación y el poder predictivo de los factores de la parentalidad y de la coparentalidad en los síntomas clínicos de ansiedad y depresión en los niños. Los participantes, 50 individuos que conviven con su pareja y tienen al menos un hijo, de entre 7 y 11 años, completaron una herramienta que se compone de seis escalas que evaluaban la crianza, la coparentalidad y la sintomatología en sus hijos. Los resultados indicaron correlaciones bajas y moderadas entre los factores de la parentalidad y de la coparentalidad y los síntomas emocionales y conductuales de los niños. El conflicto familiar coparental y la supervisión del comportamiento fueron predictores del 16% de los síntomas de ansiedad generalizada en la descendencia y la triangulación familiar del 17% de los síntomas de depresión. Esto coincide con la literatura al indicar que los niños son susceptibles a la calidad del funcionamiento de los subsistemas parental y coparental.(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Ansiedade , Criança , Poder Familiar , Depressão , Relações Pais-Filho , Apetite , Psicologia , Carência Psicossocial , Associação , Transtorno do Deficit de Atenção com Hiperatividade , Sinais e Sintomas , Apoio Social , Socialização , Comportamento , Sintomas Comportamentais , Poder Psicológico , Família , Maus-Tratos Infantis , Desenvolvimento Infantil , Educação Infantil , Proteção da Criança , Causalidade , Transtorno da Conduta , Aconselhamento , Impacto Psicossocial , Carga Genética , Amigos , Transtorno Depressivo , Diagnóstico , Educação não Profissionalizante , Meio Ambiente , Conflito Familiar , Medo , Bullying , Transtorno de Aprendizagem Específico , Análise de Dados , Relações Interpessoais , Ira , Deficiências da Aprendizagem , Transtornos MentaisRESUMO
AbstractDeleterious genetic variation is abundant in wild populations, and understanding the ecological and conservation implications of such variation is an area of active research. Genomic methods are increasingly used to quantify the impacts of deleterious variation in natural populations; however, these approaches remain limited by an inability to accurately predict the selective and dominance effects of mutations. Computational simulations of deleterious variation offer a complementary tool that can help overcome these limitations, although such approaches have yet to be widely employed. In this perspective article, we aim to encourage ecological and conservation genomics researchers to adopt greater use of computational simulations to aid in deepening our understanding of deleterious variation in natural populations. We first provide an overview of the components of a simulation of deleterious variation, describing the key parameters involved in such models. Next, we discuss several approaches for validating simulation models. Finally, we compare and validate several recently proposed deleterious mutation models, demonstrating that models based on estimates of selection parameters from experimental systems are biased toward highly deleterious mutations. We describe a new model that is supported by multiple orthogonal lines of evidence and provide example scripts for implementing this model (https://github.com/ckyriazis/simulations_review).
Assuntos
Carga Genética , Genética Populacional , Variação Genética , Endogamia , Modelos Genéticos , Mutação , Seleção GenéticaRESUMO
High genetic diversity is a good predictor of long-term population viability, yet some species persevere despite having low genetic diversity. Here we study the genomic erosion of the Seychelles paradise flycatcher (Terpsiphone corvina), a species that narrowly avoided extinction after having declined to 28 individuals in the 1960s. The species recovered unassisted to over 250 individuals in the 1990s and was downlisted from Critically Endangered to Vulnerable in the International Union for the Conservation of Nature Red List in 2020. By comparing historical, prebottleneck (130+ years old) and modern genomes, we uncovered a 10-fold loss of genetic diversity. Highly deleterious mutations were partly purged during the bottleneck, but mildly deleterious mutations accumulated. The genome shows signs of historical inbreeding during the bottleneck in the 1960s, but low levels of recent inbreeding after demographic recovery. Computer simulations suggest that the species long-term small Ne reduced the masked genetic load and made the species more resilient to inbreeding and extinction. However, the reduction in genetic diversity due to the chronically small Ne and the severe bottleneck is likely to have reduced the species adaptive potential to face environmental change, which together with a higher load, compromises its long-term population viability. Thus, small ancestral Ne offers short-term bottleneck resilience but hampers long-term adaptability to environmental shifts. In light of rapid global rates of population decline, our work shows that species can continue to suffer the effect of their decline even after recovery, highlighting the importance of considering genomic erosion and computer modeling in conservation assessments.
Assuntos
Espécies em Perigo de Extinção , Variação Genética , Humanos , Animais , Carga Genética , Endogamia , Aves/genéticaRESUMO
In theoretical biology, a prevailing hypothesis posits a profound interconnection between effective population size (Ne), genetic diversity, inbreeding, and genetic load. The domestication and improvement processes are believed to be pivotal in diminishing genetic diversity while elevating levels of inbreeding and increasing genetic load. In this study, we performed a whole genome analysis to quantity genetic diversity, inbreeding, and genetic load across seven wild Ovis species and five domesticated sheep breeds. Our research demonstrates that the genetic load and diversity of species in the genus Ovis have no discernible impact on recent Ne, and three species within the subgenus Pachyceros tend to carry a higher genetic load and lower genetic diversity patterns. The results coincide with these species' dramatic decline in population sizes within the subgenus Pachyceros ~80-250 thousand years ago. European mouflon presented with the lowest Ne, lower genetic diversity, and higher individual inbreeding coefficient but a lower genetic load (missense and LoF). This suggests that the small Ne of European mouflon could reduce harmful mutations compared to other species within the genus Ovis. We showed lower genetic diversity in domesticated sheep than in Asiatic mouflon, but counterintuitive patterns of genetic load, i.e., lower weak genetic load (missense mutation) and no significant difference in strong genetic load (LoF mutation) between domestic sheep and Asiatic mouflon. These findings reveal that the "cost of domestication" during domestication and improvement processes reduced genetic diversity and purified weak genetic load more efficiently than wild species.
Assuntos
Domesticação , Carneiro Doméstico , Animais , Ovinos/genética , Carneiro Doméstico/genética , Densidade Demográfica , Carga Genética , MutaçãoRESUMO
Sexual selection on males is predicted to increase population fitness, and delay population extinction, when mating success negatively covaries with genetic load across individuals. However, such benefits of sexual selection could be counteracted by simultaneous increases in genome-wide drift resulting from reduced effective population size caused by increased variance in fitness. Resulting fixation of deleterious mutations could be greatest in small populations, and when environmental variation in mating traits partially decouples sexual selection from underlying genetic variation. The net consequences of sexual selection for genetic load and population persistence are therefore likely to be context dependent, but such variation has not been examined. We use a genetically explicit individual-based model to show that weak sexual selection can increase population persistence time compared to random mating. However, for stronger sexual selection such positive effects can be overturned by the detrimental effects of increased genome-wide drift. Furthermore, the relative strengths of mutation-purging and drift critically depend on the environmental variance in the male mating trait. Specifically, increasing environmental variance caused stronger sexual selection to elevate deleterious mutation fixation rate and mean selection coefficient, driving rapid accumulation of drift load and decreasing population persistence times. These results highlight an intricate balance between conflicting positive and negative consequences of sexual selection on genetic load, even in the absence of sexually antagonistic selection. They imply that environmental variances in key mating traits, and intrinsic genetic drift, should be properly factored into future theoretical and empirical studies of the evolution of population fitness under sexual selection.
Assuntos
Preferência de Acasalamento Animal , Seleção Sexual , Animais , Masculino , Carga Genética , Mutação , Seleção GenéticaRESUMO
Our ability to assess the threat posed by the genetic load to small and declining populations has been greatly improved by advances in genome sequencing and computational approaches. Yet, considerable confusion remains around the definitions of the genetic load and its dynamics, and how they impact individual fitness and population viability. We illustrate how both selective purging and drift affect the distribution of deleterious mutations during population size decline and recovery. We show how this impacts the composition of the genetic load, and how this affects the extinction risk and recovery potential of populations. We propose a framework to examine load dynamics and advocate for the introduction of load estimates in the management of endangered populations.
Assuntos
Carga Genética , Genética Populacional , Densidade Demográfica , Endogamia , Variação GenéticaRESUMO
Balancing selection is a form of natural selection maintaining diversity at the sites it targets and at linked nucleotide sites. Due to selection favoring heterozygosity, it has the potential to facilitate the accumulation of a "sheltered" load of tightly linked recessive deleterious mutations. However, precisely evaluating the extent of these effects has remained challenging. Taking advantage of plant self-incompatibility as one of the best-understood examples of long-term balancing selection, we provide a highly resolved picture of the genomic extent of balancing selection on the sheltered genetic load. We used targeted genome resequencing to reveal polymorphism of the genomic region flanking the self-incompatibility locus in three sample sets in each of the two closely related plant species Arabidopsis halleri and Arabidopsis lyrata, and used 100 control regions from throughout the genome to factor out differences in demographic histories and/or sample structure. Nucleotide polymorphism increased strongly around the S-locus in all sample sets, but only over a limited genomic region, as it became indistinguishable from the genomic background beyond the first 25-30â kb. Genes in this chromosomal interval exhibited no excess of mutations at 0-fold degenerated sites relative to putatively neutral sites, hence revealing no detectable weakening of the efficacy of purifying selection even for these most tightly linked genes. Overall, our results are consistent with the predictions of a narrow genomic influence of linkage to the S-locus and clarify how natural selection in one genomic region affects the evolution of the adjacent genomic regions.
Assuntos
Arabidopsis , Arabidopsis/genética , Carga Genética , Polimorfismo Genético , Seleção Genética , NucleotídeosRESUMO
OBJECTIVE: Patients with incomplete lupus erythematosus (ILE) have lupus features but insufficient criteria for SLE classification. Some patients with ILE transition to SLE, but most avoid major organ involvement. This study tested whether the milder disease course in ILE is influenced by reduced SLE risk allele genetic load. METHODS: We calculated the genetic load based on 99 SLE-associated risk alleles in European American patients with SLE (≥4 American College of Rheumatology (ACR) 1997 criteria, n=170), patients with ILE (3 ACR 1997 criteria, n=169), a subset of patients with ILE not meeting Systemic Lupus International Collaborating Clinics (SLICC) classification (ILESLICC, n=119) and healthy controls (n=133). Unweighted genetic loads were calculated as the total sum of risk alleles for each individual, while weighted genetic loads were defined as the sum of risk alleles multiplied by the natural logarithm of the previously published OR of each risk allele for SLE susceptibility. RESULTS: The median unweighted and weighted SLE risk allele genetic load was significantly greater in patients with ILE (unweighted: 81, p value=0.01; weighted: 16.3, p value=0.001) and patients with SLE (80, p value=0.02; 16.29, p value=0.0006) compared with healthy controls (78, 15.76). Patients with ILESLICC trended towards an increased genetic load, although not statistically significant (unweighted: 80, p value=0.14; weighted: 16.05, p value=0.07). However, the median genetic load did not significantly differ between ILE and SLE, and genetic load did not differentiate patients with ILE and SLE (area under the curve=0.51, p=0.78) by receiver operator characteristic analysis. CONCLUSIONS: Patients with ILE and SLE have comparable genetic loads of SLE risk loci, suggesting similar genetic predispositions between these conditions. Phenotypical differences between SLE and ILE may instead be influenced by ILE-specific variants and gene-environment interactions.
Assuntos
Lúpus Eritematoso Sistêmico , Reumatologia , Humanos , Estados Unidos , Lúpus Eritematoso Sistêmico/genética , Carga Genética , Índice de Gravidade de Doença , Progressão da DoençaRESUMO
Small populations are vulnerable to increased genetic load and drift that can lead to reductions in fitness and adaptive potential. By analyzing 66 individual whole genomes of Montezuma Quail (Cyrtonyx montezumae) from multiple populations, we illustrate how genetic load is dynamic over evolutionary time. We show that Montezuma Quail are evolving like a ring species, where the terminal extant populations from Arizona and Texas have been separated for ~16,500 years. The Texas populations have remained small but stable since the separation, whereas the Arizona population is much larger today but has been contracting for thousands of years. Most deleterious mutations across the genome are young and segregating privately in each population and a greater number of deleterious alleles are present in the larger population. Our data indicate that ancestral load is purged during strong bottlenecks, but the reduced efficiency of selection in small populations means that segregating deleterious mutations are more likely to rise in frequency over time. Forward-time simulations indicate that severe population declines in historically large populations is more detrimental to individual fitness, whereas long-term small populations are more at risk for reduced adaptive potential and population-level fitness. Our study highlights the intimate connections among evolutionary history, historical demography, genetic load, and evolutionary potential in wild populations.