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Mol Biol Evol ; 39(2)2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-34893856


Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.

Genoma , Carneiro Doméstico , Animais , Ásia , Europa (Continente) , Variação Genética , Irã (Geográfico) , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Ovinos/genética , Carneiro Doméstico/genética
Mol Biol Evol ; 38(3): 838-855, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941615


How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667-248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

Adaptação Biológica/genética , Resistência à Doença/genética , Introgressão Genética , Ovinos/genética , Animais , Evolução Biológica , Mudança Climática , Variação Genética , Filogeografia , Pneumonia/imunologia , Ovinos/imunologia
Nat Commun ; 11(1): 2815, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499537


Understanding the genetic changes underlying phenotypic variation in sheep (Ovis aries) may facilitate our efforts towards further improvement. Here, we report the deep resequencing of 248 sheep including the wild ancestor (O. orientalis), landraces, and improved breeds. We explored the sheep variome and selection signatures. We detected genomic regions harboring genes associated with distinct morphological and agronomic traits, which may be past and potential future targets of domestication, breeding, and selection. Furthermore, we found non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds. We identified PDGFD as a likely causal gene for fat deposition in the tails of sheep through transcriptome, RT-PCR, qPCR, and Western blot analyses. Our results provide insights into the demographic history of sheep and a valuable genomic resource for future genetic studies and improved genome-assisted breeding of sheep and other domestic animals.

Criação de Animais Domésticos/métodos , Animais Selvagens/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Carneiro Doméstico/genética , Alelos , Animais , Cruzamento , Feminino , Frequência do Gene , Variação Genética , Genética , Genômica , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Desequilíbrio de Ligação , Mutação , Fenótipo , Polimorfismo de Nucleotídeo Único , Seleção Genética , Análise de Sequência de DNA , Ovinos , Especificidade da Espécie , Sequenciamento Completo do Genoma
Yi Chuan ; 38(9): 831-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27644744


In animal cells, inhibition of non-homologous end joining (NHEJ) pathway improves the efficiency of homologous recombination (HR)-mediated double-strand brakes (DSBs) repair. To improve the efficiency of HR in sheep embryo fibroblasts, the NHEJ key molecule DNA ligase 4 (Lig4) was suppressed by siRNA interference. Four pairs of siRNA targeting Lig4 were designed and chemically synthesized. These siRNA were electro-transferred into sheep embryo fibroblasts respectively. Compared with the control groups, two pairs of siRNA were identified to effectively inhibit the expression of sheep Lig4 gene by qRT-PCR and Western blotting. The plasmid rejoining assay was adopted for examining the efficiency of HR-mediated DSB repair. I-SceⅠ endonuclease linearized vector and siRNA were co-transfected into sheep embryo fibroblasts. Flow cytometry analysis of cells after transfection for 72 h showed that suppression of Lig4 using siRNAs increased the rejoining efficiency of HR vector by 3-4 times compared with the control groups. Therefore, enhanced HR vector rejoining frequency by instant inhabition of Lig4 gene provides theoretical basis for improving gene targeting efficiency of sheep embryo fibroblasts.

DNA Ligases/genética , Fibroblastos/metabolismo , Recombinação Homóloga/genética , RNA Interferente Pequeno/genética , Reparo de DNA por Recombinação/genética , Ovinos/genética , Animais , Quebras de DNA de Cadeia Dupla , Dano ao DNA/genética , Proteínas de Ligação a DNA/genética , Marcação de Genes/métodos , Proteínas Nucleares/genética , Ovinos/metabolismo