A skin-linked genetic variant in sheep became more common across Europe between the Neolithic period and the Middle Ages, offering a glimpse of how thousands of years of breeding may have changed not only sheep DNA but also how genes work in different parts of the body.
For about 10,000 years, people have bred sheep for traits such as wool, size and reproductive characteristics. Yet finding how this long history shaped the animals has been difficult. DNA studies can point to genome regions linked with a trait, but often cannot show which genes are involved, how they act or where in the body their effects occur.
An international research team, including scientists from Aarhus University, has created SheepGTEx, the most comprehensive map yet of how genetic variation influences gene regulation in sheep. The atlas draws on 6,761 RNA-sequencing samples from 2,816 sheep and covers 51 tissues and cell types. RNA sequencing measures activity in genes. The researchers studied seven types of molecular regulation and identified hundreds of thousands of regulatory effects.
The atlas connects genetic variants with genes, biological processes and the tissues where they act. That detail matters because a variant can affect a gene in one tissue without producing the same effect throughout the body. Comparing patterns across tissues can help researchers understand how particular traits may be shaped.
To look back through time, the team combined the atlas with DNA from 52 ancient sheep that lived across roughly 10,000 years. The evidence suggests that domestication and selective breeding left traces not just in DNA sequences, but also in the mechanisms that control gene activity. Variants regulating genes in only one or a few tissues showed stronger signs of selection than variants affecting several tissues.
Some of the patterns involved the skin and cervix, and fit with human selection for traits linked to wool, pigmentation and reproduction. One example is THNSL2, a gene whose activity in skin is influenced by genetic variation. A variant associated with higher THNSL2 activity in modern sheep generally grew more common among European sheep from the Neolithic period to the Middle Ages, though its frequency rose and fell over time.
Because wool grows from hair follicles in the skin, the pattern offers a possible link between changes in gene regulation and the development of wool-related traits. It does not prove that the variant directly increased wool production. Lingzhao Fang, an associate professor at Aarhus University's Center for Quantitative Genetics and Genomics, said the relationship between tissue-specific regulation and signs of selection was particularly surprising.
SheepGTEx also points toward questions about traits in modern animals. Researchers reported an association involving regulation of FXYD1 in the anterior pituitary gland, a tissue that produces hormones and plays an important role in reproduction. The source account does not provide further details about that finding.
Published in Nature Genetics, the atlas gives scientists a tool to move from broad genetic signals toward specific genes and tissues. Its mix of modern sheep data and ancient DNA shows how a long history of human choices can leave a record in the fine workings of biology. Further study will be needed to test what individual variants do, but the map offers a clearer starting point for tracing those effects.