# Evolution and Comparative Analysis of Sheep Reference Genomes: From Fragmented Assemblies to Telomere-to-Telomere Genomics

## TL;DR

This paper reviews how sheep reference genomes have improved from fragmented to complete, enabling new genetic studies and better breeding strategies.

## Contribution

The paper provides a systematic comparative analysis of sheep genome assembly improvements and their impact on genetic research and breeding.

## Key findings

- Improved genome resolution allows study of complex genetic features like repetitive regions and structural changes.
- High-quality genomes enable marker-based to multi-omics trait dissection in sheep genetics.
- Telomere-to-telomere genomes offer new applications in assembly methodologies and integrative analyses.

## Abstract

High-quality reference genomes are essential tools for understanding the genetic makeup of organisms and for applying this knowledge in agriculture and biology. In sheep, reference genomes have undergone continuous improvement over the past decade, evolving from early fragmented versions to nearly complete genomes that span entire chromosomes from end to end. However, many researchers and breeders are still unclear about how these improvements have changed what can be studied and achieved in sheep genetics. In this review, we summarize the development of sheep reference genomes from early incomplete assemblies to recent near-complete genome versions. We compare different genome versions in terms of their completeness, accuracy, and practical usefulness, and explain how better genome quality has enabled new types of genetic analyses. Our analysis shows that improvements in genome resolution have made it possible to study complex genetic features that were previously inaccessible, including repetitive regions and large structural changes in the genome. Overall, this work provides a clear overview of how advances in genome technology have transformed sheep genetic research and highlights how high-quality reference genomes can support future studies, livestock improvement, and more precise breeding strategies, benefiting both science and agricultural production.

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.