The domestication and subsequent development of sheep are crucial events in the history of human civilization and the agricultural revolution. However, the impact of interspecific introgression on the genomic regions under domestication and subsequent selection remains unclear. Here, we analyze the whole genomes of domestic sheep and their wild relative species. We found introgression from wild sheep such as the snow sheep and its American relatives (bighorn and thinhorn sheep) into urial, Asiatic and European mouflons. We observed independent events of adaptive introgression from wild sheep into the Asiatic and European mouflons, as well as shared introgressed regions from both snow sheep and argali into Asiatic mouflon before or during the domestication process. We revealed European mouflons might arise through hybridization events between a now extinct sheep in Europe and feral domesticated sheep around 6000–5000 years BP. We also unveiled later introgressions from wild sheep to their sympatric domestic sheep after domestication. Several of the introgression events contain loci with candidate domestication genes (e.g.,PAPPA2,NR6A1,SH3GL3,RFX3andCAMK4), associated with morphological, immune, reproduction or production traits (wool/meat/milk). We also detected introgression events that introduced genes related to nervous response (NEURL1), neurogenesis (PRUNE2), hearing ability (USH2A), and placental viability (PAG11andPAG3) into domestic sheep and their ancestral wild species from other wild species.

Previous studies reveal extensive genetic introgression between Ovis species, which affects genetic adaptation and morphological traits. However, the exact evolutionary scenarios underlying the hybridization between sheep and allopatric wild relatives remain unknown. To address this problem, we here integrate the reference genomes of several ovine and caprine species: domestic sheep, argali, bighorn sheep, snow sheep, and domestic goats. Additionally, we use 856 whole genomes representing 169 domestic sheep populations and their 6 wild relatives: Asiatic mouflon, urial, argali, snow sheep, thinhorn sheep and bighorn sheep. We implement a comprehensive set of analyses to test introgression among these species. We infer that the argali lineage originated ca. 3.08-3.35 Mya and hybridized with the ancestor of Pachyceriforms (e.g., bighorn sheep and snow sheep) at ∼1.56 Mya. Previous studies show apparent introgression from North American Pachyceriforms into the Bashibai sheep, a Chinese native sheep breed, despite their wide geographic separation. We show here that, in fact, the apparent introgression from the Pachyceriforms into Bashibai can be explained by the old introgression from Pachyceriforms into argali, and subsequent recent introgression from argali into Bashibai. Our results illustrate the challenges of estimating complex introgression histories and provide an example of how indirect and direct introgression can be distinguished.

In theoretical biology, a prevailing hypothesis posits a profound interconnection between effective population size (N_e), 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 N_e, 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 N_e, lower genetic diversity, and higher individual inbreeding coefficient but a lower genetic load (missense and LoF). This suggests that the small N_e 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.

Background: Asiatic mouflon ( O. gmelini ) consists of several subspecies mainly distributed in Armenia, southern Azerbaijan, Cyprus, northern, southern, and western regions of Iran, and eastern and central regions of Turkey nowadays. Genome analyses of Asiatic mouflon in Iran revealed that they could have diverged from the direct ancestor of domestic sheep, and showed genetic introgression into domestic sheep after domestication. However, the impact of the Asiatic mouflon subspecies in Iran on sheep domestication remains unclear. Results: Here, we conducted a comprehensive population genomics analysis of Asiatic mouflons in Iran with 780 whole-genome sequences, 767 whole mitogenomes, and 239 Y chromosomes. Whole-genome sequence analyses revealed two subpopulations of the Asiatic mouflons in Iran: O. gmelini _2 limited in Kabudan and O. gmelini _1 over a wide geographic area. Phylogenetic analyses of the Asiatic mouflons in Iran based on uniparental variants revealed a monophyletic lineage with the mitochondrial haplogroups C+E, and clustered into a monophyletic with Y-chromosomal lineage HY2 of sheep. Additionally, introgression tests detected significant signals of genetic introgression from O. gmelini _2 to four sheep populations (e.g., Garut, Garole, Bangladeshi, and Sumatra) in South and Southeast Asia. In the four sheep populations, selective tests and introgression signals revealed that the wild introgression could have contributed to their small body size and local adaptation to the hot and humid environments in the Indian Peninsula. Conclusions: Our results suggested that the maternal haplogroups C+E and paternal lineage HY2 could have originated from the Asiatic mouflon in Iran. Also, our findings provide new insights into sheep domestication and subsequent introgressions from wild ancestors to domestic populations.

Endoderm, one of three primary germ layers of vertebrate embryos, makes major contributions to the respiratory and gastrointestinal tracts and associated organs, including the liver and pancreas. In mammals, transcription factor (TF) SOX17 is vital for endoderm organ formation and can induce endoderm progenitor identity. Duplication of ancestral sox17 before or during the early evolution of ray-finned fishes produced paralogs sox32 and sox17 in zebrafish. Sox32 is required for specification of endoderm and progenitors of the left–right (LR) organizer (Kupffer's Vesicle, KV), with Sox17 a downstream target of Sox32 implicated in further KV development. Phenotypic evidence, therefore, suggests functional similarities between zebrafish Sox32 and Sox17 and mammalian SOX17. Here, we directly compare these orthologs and paralogs, using the early zebrafish embryo as a biological platform for functional testing. Our results indicate that, unlike Sox32, human SOX17 cannot induce endoderm specification in zebrafish. Furthermore, using hybrid protein functional analyses, we show that Sox32 specificity for the endoderm gene regulatory network is linked to evolutionary divergence in its DNA-binding High Mobility Group domain from its paralog Sox17. Additionally, changes in the C-terminal regions of Sox32 and Sox17 underpin their differing target specificities. Finally, we establish that specific conserved peptides in the Sox17 C-terminal domain are essential for its role in establishing correct organ asymmetry. Overall, our results illuminate the molecular basis for functional divergence of Sox32 and Sox17 in vertebrate endoderm development and LR patterning, and reveal that alterations in specific domains of both TFs at different points during the evolution of fish are critical to their distinct and essential functions.

The domestication and subsequent development of sheep are crucial events in the history of human civilization and the agricultural revolution. However, the impact of interspecific introgression on the genomic regions under domestication and subsequent selection remains unclear. Here, we analyze the whole genomes of domestic sheep and all their wild relative species. We found introgression from wild sheep such as the snow sheep and its American relatives (bighorn and thinhorn sheep) into urial, Asiatic and European mouflons. We observed independent events of adaptive introgression from wild sheep into the Asiatic and European mouflons, as well as shared introgressed regions from both snow sheep and argali into Asiatic mouflon before or during the domestication process. We revealed European mouflons arose through hybridization events between a now extinct sheep in Europe and feral domesticated sheep around 6,000 – 5,000 years BP. We also unveiled later introgressions from wild sheep to their sympatric domestic sheep after domestication. Several of the introgression events contain loci with candidate domestication genes (e.g., PAPPA2 , NR6A1 , SH3GL3 , RFX3 and CAMK4 ), associated with morphological, immune, reproduction or production traits (wool/meat/milk). We also detected introgression events that introduced genes related to nervous response ( NEURL1 ), neurogenesis ( PRUNE2 ), hearing ability ( USH2A ) and placental viability ( PAG11 and PAG3 ) to domestic sheep and their ancestral wild species from other wild species.