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1.
PLoS Genet ; 16(9): e1008956, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32911491

RESUMO

The genomic diversity of the domestic dog is an invaluable resource for advancing understanding of mammalian biology, evolutionary biology, morphologic variation, and behavior. There are approximately 350 recognized breeds in the world today, many established through hybridization and selection followed by intense breeding programs aimed at retaining or enhancing specific traits. As a result, many breeds suffer from an excess of particular diseases, one of many factors leading to the recent trend of "designer breed" development, i.e. crossing purebred dogs from existing breeds in the hope that offspring will be enriched for desired traits and characteristics of the parental breeds. We used a dense panel of 150,106 SNPs to analyze the population structure of the Australian labradoodle (ALBD), to understand how such breeds are developed. Haplotype and admixture analyses show that breeds other than the poodle (POOD) and Labrador retriever (LAB) contributed to ALBD formation, but that the breed is, at the genetic level, predominantly POOD, with all small and large varieties contributing to its construction. Allele frequency analysis reveals that the breed is enhanced for variants associated with a poodle-like coat, which is perceived by breeders to have an association with hypoallergenicity. We observed little enhancement for LAB-specific alleles. This study provides a blueprint for understanding how dog breeds are formed, highlighting the limited scope of desired traits in defining new breeds.


Assuntos
Animais Domésticos/genética , Cães/genética , Seleção Genética/genética , Alelos , Animais , Austrália , Cruzamento/métodos , Frequência do Gene/genética , Testes Genéticos , Variação Genética , Genômica , Genótipo , Haplótipos , Fenótipo , Filogenia
2.
Proc Natl Acad Sci U S A ; 117(34): 20672-20680, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32817464

RESUMO

Rapid phenotypic adaptation is often observed in natural populations and selection experiments. However, detecting the genome-wide impact of this selection is difficult since adaptation often proceeds from standing variation and selection on polygenic traits, both of which may leave faint genomic signals indistinguishable from a noisy background of genetic drift. One promising signal comes from the genome-wide covariance between allele frequency changes observable from temporal genomic data (e.g., evolve-and-resequence studies). These temporal covariances reflect how heritable fitness variation in the population leads changes in allele frequencies at one time point to be predictive of the changes at later time points, as alleles are indirectly selected due to remaining associations with selected alleles. Since genetic drift does not lead to temporal covariance, we can use these covariances to estimate what fraction of the variation in allele frequency change through time is driven by linked selection. Here, we reanalyze three selection experiments to quantify the effects of linked selection over short timescales using covariance among time points and across replicates. We estimate that at least 17 to 37% of allele frequency change is driven by selection in these experiments. Against this background of positive genome-wide temporal covariances, we also identify signals of negative temporal covariance corresponding to reversals in the direction of selection for a reasonable proportion of loci over the time course of a selection experiment. Overall, we find that in the three studies we analyzed, linked selection has a large impact on short-term allele frequency dynamics that is readily distinguishable from genetic drift.


Assuntos
Adaptação Biológica/genética , Frequência do Gene/genética , Seleção Genética/genética , Aclimatação/genética , Adaptação Fisiológica/genética , Alelos , Animais , Evolução Biológica , Evolução Molecular , Frequência do Gene/fisiologia , Deriva Genética , Genética Populacional/métodos , Genômica/métodos , Humanos , Modelos Genéticos , Herança Multifatorial/genética , Densidade Demográfica
3.
Proc Natl Acad Sci U S A ; 117(36): 22303-22310, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32817535

RESUMO

Penguins are the only extant family of flightless diving birds. They currently comprise at least 18 species, distributed from polar to tropical environments in the Southern Hemisphere. The history of their diversification and adaptation to these diverse environments remains controversial. We used 22 new genomes from 18 penguin species to reconstruct the order, timing, and location of their diversification, to track changes in their thermal niches through time, and to test for associated adaptation across the genome. Our results indicate that the penguin crown-group originated during the Miocene in New Zealand and Australia, not in Antarctica as previously thought, and that Aptenodytes is the sister group to all other extant penguin species. We show that lineage diversification in penguins was largely driven by changing climatic conditions and by the opening of the Drake Passage and associated intensification of the Antarctic Circumpolar Current (ACC). Penguin species have introgressed throughout much of their evolutionary history, following the direction of the ACC, which might have promoted dispersal and admixture. Changes in thermal niches were accompanied by adaptations in genes that govern thermoregulation and oxygen metabolism. Estimates of ancestral effective population sizes (N e ) confirm that penguins are sensitive to climate shifts, as represented by three different demographic trajectories in deeper time, the most common (in 11 of 18 penguin species) being an increased N e between 40 and 70 kya, followed by a precipitous decline during the Last Glacial Maximum. The latter effect is most likely a consequence of the overall decline in marine productivity following the last glaciation.


Assuntos
Evolução Molecular , Genoma/genética , Spheniscidae , Animais , Regiões Antárticas , Austrália , Mudança Climática , Ecossistema , Estudo de Associação Genômica Ampla , Nova Zelândia , Filogenia , Seleção Genética/genética , Spheniscidae/classificação , Spheniscidae/genética , Spheniscidae/fisiologia
4.
Proc Natl Acad Sci U S A ; 117(36): 22323-22330, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32848059

RESUMO

Distinguishing which traits have evolved under natural selection, as opposed to neutral evolution, is a major goal of evolutionary biology. Several tests have been proposed to accomplish this, but these either rely on false assumptions or suffer from low power. Here, I introduce an approach to detecting selection that makes minimal assumptions and only requires phenotypic data from ∼10 individuals. The test compares the phenotypic difference between two populations to what would be expected by chance under neutral evolution, which can be estimated from the phenotypic distribution of an F2 cross between those populations. Simulations show that the test is robust to variation in the number of loci affecting the trait, the distribution of locus effect sizes, heritability, dominance, and epistasis. Comparing its performance to the QTL sign test-an existing test of selection that requires both genotype and phenotype data-the new test achieves comparable power with 50- to 100-fold fewer individuals (and no genotype data). Applying the test to empirical data spanning over a century shows strong directional selection in many crops, as well as on naturally selected traits such as head shape in Hawaiian Drosophila and skin color in humans. Applied to gene expression data, the test reveals that the strength of stabilizing selection acting on mRNA levels in a species is strongly associated with that species' effective population size. In sum, this test is applicable to phenotypic data from almost any genetic cross, allowing selection to be detected more easily and powerfully than previously possible.


Assuntos
Cruzamentos Genéticos , Modelos Genéticos , Seleção Genética/genética , Animais , Produtos Agrícolas/genética , Drosophila/anatomia & histologia , Drosophila/genética , Evolução Molecular , Variação Genética/genética , Humanos , Fenótipo , Locos de Características Quantitativas/genética , Característica Quantitativa Herdável , Saccharomyces cerevisiae/genética , Pigmentação da Pele/genética
5.
PLoS Pathog ; 16(8): e1008718, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32797103

RESUMO

APOBEC3 enzymes are innate immune effectors that introduce mutations into viral genomes. These enzymes are cytidine deaminases which transform cytosine into uracil. They preferentially mutate cytidine preceded by thymidine making the 5'TC motif their favored target. Viruses have evolved different strategies to evade APOBEC3 restriction. Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. Hence, the APOBEC3s left on the genome of certain viruses an evolutionary footprint. The aim of our study is the identification of these viruses having a genome shaped by the APOBEC3s. We analyzed the genome of 33,400 human viruses for the depletion of APOBEC3-favored motifs. We demonstrate that the APOBEC3 selection pressure impacts at least 22% of all currently annotated human viral species. The papillomaviridae and polyomaviridae are the most intensively footprinted families; evidencing a selection pressure acting genome-wide and on both strands. Members of the parvoviridae family are differentially targeted in term of both magnitude and localization of the footprint. Interestingly, a massive APOBEC3 footprint is present on both strands of the B19 erythroparvovirus; making this viral genome one of the most cleaned sequences for APOBEC3-favored motifs. We also identified the endemic coronaviridae as significantly footprinted. Interestingly, no such footprint has been detected on the zoonotic MERS-CoV, SARS-CoV-1 and SARS-CoV-2 coronaviruses. In addition to viruses that are footprinted genome-wide, certain viruses are footprinted only on very short sections of their genome. That is the case for the gamma-herpesviridae and adenoviridae where the footprint is localized on the lytic origins of replication. A mild footprint can also be detected on the negative strand of the reverse transcribing HIV-1, HIV-2, HTLV-1 and HBV viruses. Together, our data illustrate the extent of the APOBEC3 selection pressure on the human viruses and identify new putatively APOBEC3-targeted viruses.


Assuntos
Citidina Desaminase/metabolismo , Genoma Viral/genética , Interações Hospedeiro-Patógeno/genética , Seleção Genética/genética , Replicação Viral/genética , Coronaviridae/genética , Humanos , Imunidade Inata/imunologia , Papillomaviridae/genética , Parvoviridae/genética , Polyomaviridae/genética , Proteínas Virais/genética
6.
PLoS One ; 15(8): e0236351, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785293

RESUMO

Hybrid performance during wheat breeding can be improved by analyzing genetic distance (GD) among wheat genotypes and determining its correlation with heterosis. This study evaluated the GD between 16 wheat genotypes by using 60 simple sequence repeat (SSR) markers to classify them according to their relationships and select those with greater genetic diversity, evaluate the correlation of the SSR marker distance with heterotic performance and specific combining ability (SCA) for heat stress tolerance, and identify traits that most influence grain yield (GY). Eight parental genotypes with greater genetic diversity and their 28 F1 hybrids generated using diallel crossing were evaluated for 12 measured traits in two seasons. The GD varied from 0.235 to 0.911 across the 16 genotypes. Cluster analysis based on the GD estimated using SSRs classified the genotypes into three major groups and six sub-groups, almost consistent with the results of principal coordinate analysis. The combined data indicated that five hybrids showed 20% greater yield than mid-parent or better-parent. Two hybrids (P2 × P4) and (P2 × P5), which showed the highest performance of days to heading (DH), grain filling duration (GFD), and GY, and had large genetic diversity among themselves (0.883 and 0.911, respectively), were deemed as promising heat-tolerant hybrids. They showed the best mid-parent heterosis and better-parent heterosis (BPH) for DH (-11.57 and -7.65%; -13.39 and -8.36%, respectively), GFD (12.74 and 12.17%; 12.09 and 10.59%, respectively), and GY (36.04 and 20.04%; 44.06 and 37.73%, respectively). Correlation between GD and each of BPH and SCA effects based on SSR markers was significantly positive for GFD, hundred kernel weight, number of kernels per spike, harvest index, GY, and grain filling rate and was significantly negative for DH. These correlations indicate that the performance of wheat hybrids with high GY and earliness could be predicted by determining the GD of the parents by using SSR markers. Multivariate analysis (stepwise regression and path coefficient) suggested that GFD, hundred kernel weight, days to maturity, and number of kernels per spike had the highest influence on GY.


Assuntos
Resposta ao Choque Térmico/genética , Vigor Híbrido/genética , Seleção Genética/genética , Triticum/genética , Pão , Cruzamento , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Flores/genética , Flores/crescimento & desenvolvimento , Genótipo , Humanos , Hibridização Genética/genética , Repetições de Microssatélites/genética , Fenótipo , Triticum/crescimento & desenvolvimento
7.
PLoS Genet ; 16(8): e1008987, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32853297

RESUMO

Replication-transcription conflicts promote mutagenesis and give rise to evolutionary signatures, with fundamental importance to genome stability ranging from bacteria to metastatic cancer cells. This review focuses on the interplay between replication-transcription conflicts and the evolution of gene directionality. In most bacteria, the majority of genes are encoded on the leading strand of replication such that their transcription is co-directional with the direction of DNA replication fork movement. This gene strand bias arises primarily due to negative selection against deleterious consequences of head-on replication-transcription conflict. However, many genes remain head-on. Can head-on orientation provide some benefit? We combine insights from both mechanistic and evolutionary studies, review published work, and analyze gene expression data to evaluate an emerging model that head-on genes are temporal targets for adaptive mutagenesis during stress. We highlight the alternative explanation that genes in the head-on orientation may simply be the result of genomic inversions and relaxed selection acting on nonessential genes. We seek to clarify how the mechanisms of replication-transcription conflict, in concert with other mutagenic mechanisms, balanced by natural selection, have shaped bacterial genome evolution.


Assuntos
Replicação do DNA/genética , Evolução Molecular , Seleção Genética/genética , Transcrição Genética , Bactérias/genética , Genoma Bacteriano/genética
8.
Am J Hum Genet ; 107(3): 473-486, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32781046

RESUMO

Africa contains more human genetic variation than any other continent, but the majority of the population-scale analyses of the African peoples have focused on just two of the four major linguistic groups, the Niger-Congo and Afro-Asiatic, leaving the Nilo-Saharan and Khoisan populations under-represented. In order to assess genetic variation and signatures of selection within a Nilo-Saharan population and between the Nilo-Saharan and Niger-Congo and Afro-Asiatic, we sequenced 50 genomes from the Nilo-Saharan Lugbara population of North-West Uganda and 250 genomes from 6 previously unsequenced Niger-Congo populations. We compared these data to data from a further 16 Eurasian and African populations including the Gumuz, another putative Nilo-Saharan population from Ethiopia. Of the 21 million variants identified in the Nilo-Saharan population, 3.57 million (17%) were not represented in dbSNP and included predicted non-synonymous mutations with possible phenotypic effects. We found greater genetic differentiation between the Nilo-Saharan Lugbara and Gumuz populations than between any two Afro-Asiatic or Niger-Congo populations. F3 tests showed that Gumuz contributed a genetic component to most Niger-Congo B populations whereas Lugabara did not. We scanned the genomes of the Lugbara for evidence of selective sweeps. We found selective sweeps at four loci (SLC24A5, SNX13, TYRP1, and UVRAG) associated with skin pigmentation, three of which already have been reported to be under selection. These selective sweeps point toward adaptations to the intense UV radiation of the Sahel.


Assuntos
Adaptação Fisiológica/genética , Variação Genética/genética , Seleção Genética/genética , Pigmentação da Pele/genética , Grupo com Ancestrais do Continente Africano/genética , Antiporters/genética , Gerenciamento de Dados , Etiópia/epidemiologia , Feminino , Genética Populacional , Genoma Humano/genética , Haplótipos/genética , Humanos , Masculino , Glicoproteínas de Membrana/genética , Oxirredutases/genética , Polimorfismo de Nucleotídeo Único/genética , Nexinas de Classificação/genética , Proteínas Supressoras de Tumor/genética , Uganda/epidemiologia
9.
Nat Med ; 26(8): 1240-1246, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32601336

RESUMO

The conserved region of influenza hemagglutinin (HA) stalk (or stem) has gained attention as a potent target for universal influenza vaccines1-5. Although the HA stalk region is relatively well conserved, the evolutionarily dynamic nature of influenza viruses6 raises concerns about the possible emergence of viruses carrying stalk escape mutation(s) under sufficient immune pressure. Here we show that immune pressure on the HA stalk can lead to expansion of escape mutant viruses in study participants challenged with a 2009 H1N1 pandemic influenza virus inoculum containing an A388V polymorphism in the HA stalk (45% wild type and 55% mutant). High level of stalk antibody titers was associated with the selection of the mutant virus both in humans and in vitro. Although the mutant virus showed slightly decreased replication in mice, it was not observed in cell culture, ferrets or human challenge participants. The A388V mutation conferred resistance to some of the potent HA stalk broadly neutralizing monoclonal antibodies (bNAbs). Co-culture of wild-type and mutant viruses in the presence of either a bNAb or human serum resulted in rapid expansion of the mutant. These data shed light on a potential obstacle for the success of HA-stalk-targeting universal influenza vaccines-viral escape from vaccine-induced stalk immunity.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/genética , Seleção Genética/genética , Animais , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , Sequência Conservada/genética , Reações Cruzadas/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Camundongos , Seleção Genética/imunologia
10.
Nat Immunol ; 21(8): 857-867, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32601469

RESUMO

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by homozygous or compound heterozygous gain-of-function mutations in MEFV, which encodes pyrin, an inflammasome protein. Heterozygous carrier frequencies for multiple MEFV mutations are high in several Mediterranean populations, suggesting that they confer selective advantage. Among 2,313 Turkish people, we found extended haplotype homozygosity flanking FMF-associated mutations, indicating evolutionarily recent positive selection of FMF-associated mutations. Two pathogenic pyrin variants independently arose >1,800 years ago. Mutant pyrin interacts less avidly with Yersinia pestis virulence factor YopM than with wild-type human pyrin, thereby attenuating YopM-induced interleukin (IL)-1ß suppression. Relative to healthy controls, leukocytes from patients with FMF harboring homozygous or compound heterozygous mutations and from asymptomatic heterozygous carriers released heightened IL-1ß specifically in response to Y. pestis. Y. pestis-infected MefvM680I/M680I FMF knock-in mice exhibited IL-1-dependent increased survival relative to wild-type knock-in mice. Thus, FMF mutations that were positively selected in Mediterranean populations confer heightened resistance to Y. pestis.


Assuntos
Resistência à Doença/genética , Febre Familiar do Mediterrâneo/genética , Peste , Pirina/genética , Seleção Genética/genética , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas da Membrana Bacteriana Externa/metabolismo , Resistência à Doença/imunologia , Haplótipos , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Peste/imunologia , Peste/metabolismo , Pirina/imunologia , Pirina/metabolismo , Turquia , Fatores de Virulência/imunologia , Fatores de Virulência/metabolismo , Yersinia pestis
11.
Proc Natl Acad Sci U S A ; 117(31): 18582-18590, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32680961

RESUMO

Cells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations of Escherichia coli with genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.


Assuntos
Adaptação Biológica/genética , Evolução Molecular , Modelos Genéticos , Seleção Genética/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Mutação/genética , Fator Tu de Elongação de Peptídeos/genética , Biossíntese de Proteínas/genética
12.
PLoS One ; 15(6): e0234504, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542006

RESUMO

The continual loss of threatened biodiversity is occurring at an accelerated pace. High-throughput sequencing technologies are now providing opportunities to address this issue by aiding in the generation of molecular data for many understudied species of high conservation interest. Our overall goal of this study was to begin building the genomic resources to continue investigations and conservation of the Spot-Tailed Earless lizard. Here we leverage the power of high-throughput sequencing to generate the liver transcriptome for the Northern Spot-Tailed Earless Lizard (Holbrookia lacerata) and Southern Spot-Tailed Earless Lizard (Holbrookia subcaudalis), which have declined in abundance in the past decades, and their sister species, the Common Lesser Earless Lizard (Holbrookia maculata). Our efforts produced high quality and robust transcriptome assemblies validated by 1) quantifying the number of processed reads represented in the transcriptome assembly and 2) quantifying the number of highly conserved single-copy orthologs that are present in our transcript set using the BUSCO pipeline. We found 1,361 1-to-1 orthologs among the three Holbrookia species, Anolis carolinensis, and Sceloporus undulatus. We carried out dN/dS selection tests using a branch-sites model and identified a dozen genes that experienced positive selection in the Holbrookia lineage with functions in development, immunity, and metabolism. Our single-copy orthologous sequences additionally revealed significant pairwise sequence divergence (~.73%) between the Northern H. lacerata and Southern H. subcaudalis that further supports the recent elevation of the Southern Spot-Tailed Earless Lizard to full species.


Assuntos
Biodiversidade , Lagartos/genética , Seleção Genética/genética , Transcriptoma/genética , Animais , Genoma/genética , Sequenciamento de Nucleotídeos em Larga Escala , Lagartos/crescimento & desenvolvimento , Filogenia , Análise de Sequência de RNA , Sequenciamento Completo do Exoma
13.
Genet Sel Evol ; 52(1): 31, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527317

RESUMO

BACKGROUND: The traditional way to estimate variance components (VC) is based on the animal model using a pedigree-based relationship matrix (A) (A-AM). After genomic selection was introduced into breeding programs, it was anticipated that VC estimates from A-AM would be biased because the effect of selection based on genomic information is not captured. The single-step method (H-AM), which uses an H matrix as (co)variance matrix, can be used as an alternative to estimate VC. Here, we compared VC estimates from A-AM and H-AM and investigated the effect of genomic selection, genotyping strategy and genotyping proportion on the estimation of VC from the two methods, by analyzing a dataset from a commercial broiler line and a simulated dataset that mimicked the broiler population. RESULTS: VC estimates from H-AM were severely overestimated with a high proportion of selective genotyping, and overestimation increased as proportion of genotyping increased in the analysis of both commercial and simulated data. This bias in H-AM estimates arises when selective genotyping is used to construct the H-matrix, regardless of whether selective genotyping is applied or not in the selection process. For simulated populations under genomic selection, estimates of genetic variance from A-AM were also significantly overestimated when the effect of genomic selection was strong. Our results suggest that VC estimates from H-AM under random genotyping have the expected values. Predicted breeding values from H-AM were inflated when VC estimates were biased, and inflation differed between genotyped and ungenotyped animals, which can lead to suboptimal selection decisions. CONCLUSIONS: We conclude that VC estimates from H-AM are biased with selective genotyping, but are close to expected values with random genotyping.VC estimates from A-AM in populations under genomic selection are also biased but to a much lesser degree. Therefore, we recommend the use of H-AM with random genotyping to estimate VC for populations under genomic selection. Our results indicate that it is still possible to use selective genotyping in selection, but then VC estimation should avoid the use of genotypes from one side only of the distribution of phenotypes. Hence, a dual genotyping strategy may be needed to address both selection and VC estimation.


Assuntos
Cruzamento/métodos , Técnicas de Genotipagem/métodos , Seleção Genética/genética , Análise de Variância , Animais , Galinhas/genética , Simulação por Computador , Genoma/genética , Genômica/métodos , Genótipo , Modelos Animais , Modelos Genéticos , Linhagem , Fenótipo
14.
Genet Sel Evol ; 52(1): 32, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576143

RESUMO

BACKGROUND: Cattle international genetic evaluations allow the comparison of estimated breeding values (EBV) across different environments, i.e. countries. For international evaluations, across-country genetic correlations (rg) need to be estimated. However, lack of convergence of the estimated parameters and high standard errors of the rg are often experienced for beef cattle populations due to limited across-country genetic connections. Furthermore, using all available genetic connections to estimate rg is prohibitive due to computational constraints, thus sub-setting the data is necessary. Our objective was to investigate and compare the impact of strategies of data sub-setting on estimated across-country rg and their computational requirements. METHODS: Phenotype and pedigree information for age-adjusted weaning weight was available for ten European countries and 3,128,338 Limousin beef cattle males and females. Using a Monte Carlo based expectation-maximization restricted maximum likelihood (MC EM REML) methodology, we estimated across-country rg by using a multi-trait animal model where countries are modelled as different correlated traits. Values of rg were estimated using the full data and four different sub-setting strategies that aimed at selecting the most connected herds from the largest population. RESULTS: Using all available data, direct and maternal rg (standard errors in parentheses) were on average equal to 0.79 (0.14) and 0.71 (0.19), respectively. Direct-maternal within-country and between-country rg were on average equal to - 0.12 (0.09) and 0.00 (0.14), respectively. Data sub-setting scenarios gave similar results: on average, estimated rg were smaller compared to using all data for direct (0.02) and maternal (0.05) genetic effects. The largest differences were obtained for the direct-maternal within-country and between-country rg, which were, on average 0.13 and 0.12 smaller compared to values obtained by using all data. Standard errors always increased when reducing the data, by 0.02 to 0.06, on average. The proposed sub-setting strategies reduced the required computing time up to 22% compared to using all data. CONCLUSIONS: Estimating all 120 across-country rg that are required for beef cattle international evaluations, using a multi-trait MC EM REML approach, is feasible but involves long computing time. We propose four strategies to reduce computational requirements while keeping a multi-trait estimation approach. In all scenarios with data sub-setting, the estimated rg were consistently smaller (mainly for direct-maternal rg) and had larger standard errors.


Assuntos
Bovinos/genética , Técnicas de Genotipagem/métodos , Seleção Genética/genética , Algoritmos , Animais , Peso Corporal , Cruzamento , Europa (Continente) , Feminino , Genoma/genética , Genômica/métodos , Genótipo , Masculino , Modelos Genéticos , Método de Monte Carlo , Linhagem , Fenótipo , Carne Vermelha , Desmame
15.
Genet Sel Evol ; 52(1): 33, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591011

RESUMO

BACKGROUND: Natural and artificial directional selection in cosmopolitan and autochthonous pig breeds and wild boars have shaped their genomes and resulted in a reservoir of animal genetic diversity. Signatures of selection are the result of these selection events that have contributed to the adaptation of breeds to different environments and production systems. In this study, we analysed the genome variability of 19 European autochthonous pig breeds (Alentejana, Bísara, Majorcan Black, Basque, Gascon, Apulo-Calabrese, Casertana, Cinta Senese, Mora Romagnola, Nero Siciliano, Sarda, Krskopolje pig, Black Slavonian, Turopolje, Moravka, Swallow-Bellied Mangalitsa, Schwäbisch-Hällisches Schwein, Lithuanian indigenous wattle and Lithuanian White old type) from nine countries, three European commercial breeds (Italian Large White, Italian Landrace and Italian Duroc), and European wild boars, by mining whole-genome sequencing data obtained by using a DNA-pool sequencing approach. Signatures of selection were identified by using a single-breed approach with two statistics [within-breed pooled heterozygosity (HP) and fixation index (FST)] and group-based FST approaches, which compare groups of breeds defined according to external traits and use/specialization/type. RESULTS: We detected more than 22 million single nucleotide polymorphisms (SNPs) across the 23 compared populations and identified 359 chromosome regions showing signatures of selection. These regions harbour genes that are already known or new genes that are under selection and relevant for the domestication process in this species, and that affect several morphological and physiological traits (e.g. coat colours and patterns, body size, number of vertebrae and teats, ear size and conformation, reproductive traits, growth and fat deposition traits). Wild boar related signatures of selection were detected across all the genome of several autochthonous breeds, which suggests that crossbreeding (accidental or deliberate) occurred with wild boars. CONCLUSIONS: Our findings provide a catalogue of genetic variants of many European pig populations and identify genome regions that can explain, at least in part, the phenotypic diversity of these genetic resources.


Assuntos
Técnicas de Genotipagem/métodos , Seleção Genética/genética , Suínos/genética , Aclimatação/genética , Adaptação Fisiológica/genética , Algoritmos , Animais , Cruzamento , Domesticação , Europa (Continente) , Feminino , Genoma/genética , Genômica/métodos , Genótipo , Masculino , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Sequenciamento Completo do Genoma/métodos
16.
Am J Hum Genet ; 107(1): 83-95, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32516569

RESUMO

Synonymous codon usage has been identified as a determinant of translational efficiency and mRNA stability in model organisms and human cell lines. However, whether natural selection shapes human codon content to optimize translation efficiency is unclear. Furthermore, aside from those that affect splicing, synonymous mutations are typically ignored as potential contributors to disease. Using genetic sequencing data from nearly 200,000 individuals, we uncover clear evidence that natural selection optimizes codon content in the human genome. In deriving intolerance metrics to quantify gene-level constraint on synonymous variation, we discover that dosage-sensitive genes, DNA-damage-response genes, and cell-cycle-regulated genes are particularly intolerant to synonymous variation. Notably, we illustrate that reductions in codon optimality in BRCA1 can attenuate its function. Our results reveal that synonymous mutations most likely play an underappreciated role in human variation.


Assuntos
Uso do Códon/genética , Genoma Humano/genética , Seleção Genética/genética , Códon/genética , Evolução Molecular , Humanos , Mutação/genética , Processamento de RNA/genética , Estabilidade de RNA/genética
17.
Am J Hum Genet ; 107(1): 60-71, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32533944

RESUMO

Adult height is one of the earliest putative examples of polygenic adaptation in humans. However, this conclusion was recently challenged because residual uncorrected stratification from large-scale consortium studies was considered responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. We re-examined this question, focusing on one of the shortest European populations, the Sardinians, in addition to mainland European populations. We utilized height-associated loci from the Biobank Japan (BBJ) dataset to further alleviate concerns of biased ascertainment of GWAS loci and showed that the Sardinians remain significantly shorter than expected under neutrality (∼0.22 standard deviation shorter than Utah residents with ancestry from northern and western Europe [CEU] on the basis of polygenic height scores, p = 3.89 × 10-4). We also found the trajectory of polygenic height scores between the Sardinian and the British populations diverged over at least the last 10,000 years (p = 0.0082), consistent with a signature of polygenic adaptation driven primarily by the Sardinian population. Although the polygenic score-based analysis showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in the UK population by using a haplotype-based statistic, the trait singleton density score (tSDS), driven by the height-increasing alleles (p = 9.1 × 10-4). In summary, by ascertaining height loci in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, the adaptive signature was detected in haplotype-based analysis but not in polygenic score-based analysis.


Assuntos
Adaptação Fisiológica/genética , Estatura/genética , Herança Multifatorial/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Bancos de Espécimes Biológicos , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional/métodos , Genoma Humano/genética , Estudo de Associação Genômica Ampla/métodos , Haplótipos/genética , Humanos , Itália , Japão , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Seleção Genética/genética
18.
Viruses ; 12(5)2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32414076

RESUMO

Bovine coronavirus (BCoV) is widespread in cattle and wild ruminant populations throughout the world. The virus causes neonatal calf diarrhea and winter dysentery in adult cattle, as well as upper and lower respiratory tract infection in young cattle. We isolated and deep sequenced whole genomes of BCoV from calves with respiratory distress in the south-west of France and conducted a comparative genome analysis using globally collected BCoV sequences to provide insights into the genomic characteristics, evolutionary origins, and global diversity of BCoV. Molecular clock analyses allowed us to estimate that the BCoV ancestor emerged in the 1940s, and that two geographically distinct lineages diverged from the 1960s-1970s. A recombination event in the spike gene (breakpoint at nt 1100) may be at the origin of the genetic divergence sixty years ago. Little evidence of genetic mixing between the spatially segregated lineages was found, suggesting that BCoV genetic diversity is a result of a global transmission pathway that occurred during the last century. However, we found variation in evolution rates between the European and non-European lineages indicating differences in virus ecology.


Assuntos
Doenças dos Bovinos/epidemiologia , Infecções por Coronavirus/epidemiologia , Coronavirus Bovino/genética , Gastroenteropatias/epidemiologia , Gastroenteropatias/veterinária , Infecções Respiratórias/epidemiologia , Animais , Bovinos , Doenças dos Bovinos/transmissão , Infecções por Coronavirus/transmissão , Coronavirus Bovino/patogenicidade , Evolução Molecular , França/epidemiologia , Genoma Viral/genética , Geografia , Filogenia , Infecções Respiratórias/transmissão , Infecções Respiratórias/veterinária , Seleção Genética/genética , Tropismo Viral/genética
19.
PLoS One ; 15(5): e0232818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407352

RESUMO

Breeding for yield and fruit quality traits in passion fruits is complex due to the polygenic nature of these traits and the existence of genetic correlations among them. Therefore, studies focused on crop management practices and breeding using modern quantitative genetic approaches are still needed, especially for Passiflora alata, an understudied crop, popularly known as the sweet passion fruit. It is highly appreciated for its typical aroma and flavor characteristics. In this study, we aimed to reevaluate 30 genotypes previously selected for fruit quality from a 100 full-sib sweet passion fruit progeny in three environments, with a view to estimating the heritability and genetic correlations, and investigating the GEI and response to selection for nine fruit traits (weight, diameter and length of the fruit; thickness and weight of skin; weight and yield of fruit pulp; soluble solids, and yield). Pairwise genetic correlations among the fruit traits showed mostly intermediate to high values, especially those associated with fruit size and shape. Different genotype rankings were obtained regarding the predicted genetic values of weight of skin, thickness of skin and weight of pulp in each environment. Finally, we used a multiplicative selection index to select simultaneously for weight of pulp and against fruit skin thickness and weight. The response to selection was positive for all traits except soluble solids, and the 20% superior (six) genotypes were ranked. Based on the assumption that incompatibility mechanisms exist in P. alata, the selected genotypes were intercrossed in a complete diallel mating scheme. It is worth noting that all genotypes produced fruits, which is essential to guarantee yields in commercial orchards.


Assuntos
Frutas/genética , Interação Gene-Ambiente , Passiflora/genética , Cruzamento , Capsicum/genética , Capsicum/crescimento & desenvolvimento , Frutas/crescimento & desenvolvimento , Variação Genética/genética , Genótipo , Passiflora/crescimento & desenvolvimento , Seleção Genética/genética
20.
Genet Sel Evol ; 52(1): 26, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414320

RESUMO

BACKGROUND: Estimating the genetic component of a complex phenotype is a complicated problem, mainly because there are many allele effects to estimate from a limited number of phenotypes. In spite of this difficulty, linear methods with variable selection have been able to give good predictions of additive effects of individuals. However, prediction of non-additive genetic effects is challenging with the usual prediction methods. In machine learning, non-additive relations between inputs can be modeled with neural networks. We developed a novel method (NetSparse) that uses Bayesian neural networks with variable selection for the prediction of genotypic values of individuals, including non-additive genetic effects. RESULTS: We simulated several populations with different phenotypic models and compared NetSparse to genomic best linear unbiased prediction (GBLUP), BayesB, their dominance variants, and an additive by additive method. We found that when the number of QTL was relatively small (10 or 100), NetSparse had 2 to 28 percentage points higher accuracy than the reference methods. For scenarios that included dominance or epistatic effects, NetSparse had 0.0 to 3.9 percentage points higher accuracy for predicting phenotypes than the reference methods, except in scenarios with extreme overdominance, for which reference methods that explicitly model dominance had 6 percentage points higher accuracy than NetSparse. CONCLUSIONS: Bayesian neural networks with variable selection are promising for prediction of the genetic component of complex traits in animal breeding, and their performance is robust across different genetic models. However, their large computational costs can hinder their use in practice.


Assuntos
Previsões/métodos , Herança Multifatorial/genética , Fenótipo , Algoritmos , Alelos , Animais , Teorema de Bayes , Frequência do Gene/genética , Genética Populacional/métodos , Genômica/métodos , Genótipo , Humanos , Modelos Genéticos , Redes Neurais de Computação , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Seleção Genética/genética
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