Sheep (Ovis aries) were domesticated around 10,000 years ago and have since become an integral part of human agriculture, providing essential resources, such as wool, meat, and milk. Over the past century, advances in communication and agricultural productivity have driven the evolution of selective breeding practices, further enhancing the value of sheep in the global economy. Recently, the rapid development of whole-genome resequencing (WGR) technologies has significantly accelerated research in sheep molecular biology, facilitating the discovery of genetic underpinnings for critical traits. This review offers a comprehensive overview of the evolution of whole-genome resequencing and its application to sheep genetics. It explores the domestication and genetic origins of sheep, examines the genetic structure and differentiation of various sheep populations, and discusses the use of WGR in the development of genetic maps. In particular, the review highlights how WGR technology has advanced our understanding of key traits, such as wool production, lactation, reproductive performance, disease resistance, and environmental adaptability. The review also covers the use of WGR technology in the conservation and sustainable utilization of sheep genetic resources, offering valuable insights for future breeding programs aimed at enhancing the genetic diversity and resilience of sheep populations.

Goats (Capra hircus) are a widely distributed livestock known for their exceptional environmental adaptability. This review presents an integrated overview of recent advances in understanding the genetic and molecular mechanisms underlying goat adaptation to heat, cold, and high-altitude hypoxia. We first discuss the development of high-quality reference genomes, including recent telomere-to-telomere assemblies. We then examine major adaptive genes such as HSP70, ACTHR, EPAS1, SLC2A1, FGF12, and UCP1, and their roles in thermoregulation, oxygen metabolism, and stress resistance. Additionally, the review explores the synergistic role of immune signaling pathways in environmental adaptation, as well as the regulatory effects of epigenetic mechanisms such as DNA methylation, histone modification, and non-coding RNAs. Future efforts should focus on integrating multi-omics data to uncover the complex molecular networks involved in goat adaptation. This comprehensive synthesis offers valuable insights for precision breeding and long-term sustainability in the context of environmental challenges and climate change.

Multi-omics studies have multiplied associations, but many still lack causal resolution and a clear path to application. We present a practical roadmap built on four sequential steps: first, identify signals from genome-wide association studies; second, confirm these signals through regulatory colocalization and transcriptome-wide association analyses; third, integrate the evidence using network analyses and causal inference; and, fourth, test shortlisted candidates through functional and phenotypic validation. The roadmap is supported by three safeguards that make results reliable and reusable: containerized workflows that ensure end-to-end reproducibility, harmonization across batches with concise minimum-information records, and consistent identifier mapping with quality control across data layers. Across four classes of traits—growth and development, carcass and meat quality, reproduction, and environmental adaptation and resilience—we prioritize signals that remain robust across ancestries and environments, highlight modules with explicit regulatory support, and advance candidates that have already progressed to functional testing. Two application tracks follow from this process: integrating stable candidates into selection indices with context-dependent weighting, and recording and targeting mechanistic nodes for nutritional and management interventions. Taken together, this roadmap improves causal interpretability, strengthens cross-population robustness, and shortens the path from statistical association to genetic evaluation and industry uptake.

Background: The Chungtien schizothoracin (Ptychobarbus chungtienensis) is a threatened freshwater fish endemic to the Qinghai–Tibet Plateau and adjacent high-altitude regions of northwestern Yunnan, China. Although a complete mitochondrial genome of P. chungtienensis has been previously reported, direct comparison with a mitogenome generated using high-accuracy long-read sequencing can provide additional information on mitochondrial genome structure and sequence variation. This study aimed to assemble and annotate a complete mitogenome of P. chungtienensis using PacBio HiFi sequencing and to compare its mitogenomic characteristics with previously published Ptychobarbus mitogenomes. Methods: High-molecular-weight genomic DNA from a single specimen was sequenced using PacBio HiFi long-read technology. The mitochondrial genome was assembled using MitoHiFi, annotated using MitoFinder followed by manual curation, and compared with previously published Ptychobarbus mitogenomes. Phylogenetic relationships were evaluated using maximum-likelihood analysis with expanded taxon sampling, and selection pressure on the 13 mitochondrial protein-coding genes was assessed using dN/dS-based branch and branch-site models. Results: The assembled mitogenome is 16,583 bp in length and contains the typical 37 mitochondrial genes, including 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes, together with a control region and the origin of light-strand replication (O_L). The overall A + T content was 54.97%. Direct comparison with the previously reported 16,970 bp mitogenome showed that the 387 bp length difference was concentrated in non-coding regions, particularly the control region and the tRNA-Thr–tRNA-Pro intergenic region. Phylogenetic analysis based on 22 complete mitogenomes placed the newly assembled P. chungtienensis sequence in a strongly supported mitochondrial clade with Schizothorax macropogon (bootstrap = 100%), whereas the previously reported P. chungtienensis sequence clustered with P. kaznakovi (bootstrap = 100%), indicating that the two P. chungtienensis records represent distinct mitochondrial lineages. The dN/dS values of all 13 mitochondrial protein-coding genes were below 1, and neither branch nor branch–site analyses detected significant evidence of lineage-specific positive selection. Conclusions: This long-read-based mitogenome provides a high-quality genomic resource for P. chungtienensis and reveals substantial mitochondrial sequence and lineage variation among available records. These results provide a basis for comparative mitogenomic and conservation genetic studies while also indicating that species-level phylogenetic relationships and high-altitude adaptation should not be inferred from mitochondrial data alone.

The reference genome serves as a fundamental resource for sheep genetic research and molecular breeding, and iterative improvements in assembly quality have directly driven advances in these fields. A systematic literature review was conducted by retrieving relevant studies from major scientific databases using predefined keywords related to sheep reference genomes and genome assembly technologies, followed by structured screening and comparative analysis of eligible publications. This review systematically summarizes the developmental trajectory of the sheep reference genome from early fragmented assemblies to telomere-to-telomere (T2T) genome assembly approaches. Different genome versions are comparatively analyzed from multiple perspectives, including assembly strategies, quality metrics, and functional annotation. Importantly, we propose a genome-resolution-driven analytical framework that explicitly links successive improvements in reference genome completeness with paradigm shifts in sheep genetic analysis, ranging from marker-based studies to structural variation- and multi-omics-enabled trait dissection. Particular emphasis is placed on the potential applications and biological research value of T2T genomes in assembly methodologies and multi-omics integrative analyses. Furthermore, the practical significance of different reference genome versions in genetic dissection, trait mapping, and breeding applications is reviewed, and future directions for sheep genome research are discussed. This review provides both a systematic synthesis and a forward-looking conceptual roadmap for advancing sheep molecular genetics and precision breeding in the T2T genomics era.

High-altitude environments impose severe physiological challenges on mammals, yet the genetic basis of adaptation in Ethiopian indigenous cattle remains poorly understood. Here, we analyzed whole-genome resequencing data from 70 Ethiopian indigenous cattle representing seven breeds (Abigar, Barka, Boran, Felata, Fogera, Gojjam-Highland, and Horro) distributed across elevations ranging from 523 to 3410 m, obtained from the NCBI Sequence Read Archive. After alignment to the ARS-UCD2.0 reference genome, we identified 49,196,624 high-confidence SNPs and performed population genomic analyses (PCA, phylogenetic reconstruction, and ADMIXTURE), along with genome-wide selection scans using FST and nucleotide diversity (θπ), and in silico virtual knockout of candidate genes in bovine lung single-cell transcriptomics. Population structure analyses revealed marked genetic differentiation between low- and mid-to-high-altitude populations, with substantial genetic connectivity and shared ancestry among high-altitude groups. We identified 398 candidate selective regions showing concordant FST and θπ signals, encompassing 1816 candidate genes, significantly enriched in hypoxia-related and vascular remodeling pathways (phospholipase D, Ras, ErbB, Wnt, Hedgehog). Two hub candidate genes, PIK3CA and RHOA, were prioritized; virtual perturbation of PIK3CA altered extracellular matrix, focal adhesion, and integrin networks, whereas RHOA perturbation activated immune and inflammatory programs (NF-κB, phagocytosis, chemokine pathways) with upregulation of TYROBP, IL1B, TLR4, and NLRP3. Our findings indicate that Ethiopian cattle have evolved distinct genomic signatures associated with adaptation to chronic high-altitude environments, in which PIK3CA and RHOA may represent candidate regulators associated with extracellular matrix organization and immune-related transcriptional regulation, respectively, thereby providing new insights into mammalian adaptation to extreme environments.