Whole-body adipose tissue multi-omic analyses in sheep reveal molecular mechanisms underlying local adaptation to extreme environments

Abstract

The fat tail of sheep is an important organ that has evolved to adapt to extreme environments. However, the genetic mechanisms underlying the fat tail phenotype remain poorly understood. Here, we characterize transcriptome and lipidome profiles and morphological changes in 250 adipose tissues from two thin-tailed and three fat-tailed sheep populations in summer and winter. We implement whole-genome selective sweep tests to identify genetic variants related to fat-tails. We identify a set of functional genes that show differential expression in the tail fat of fat-tailed and thin-tailed sheep in summer and winter. These genes are significantly enriched in pathways, such as lipid metabolism, extracellular matrix (ECM) remodeling, molecular transport, and inflammatory response. In contrast to thin-tailed sheep, tail fat from fat-tailed sheep show slighter changes in adipocyte size, ECM remodeling, and lipid metabolism, and had less inflammation in response to seasonal changes, indicating improved homeostasis. Whole-genome selective sweep tests identify genes involved in preadipocyte commitment (e.g., BMP2, PDGFD) and terminal adipogenic differentiation (e.g., VEGFA), which could contribute to enhanced adipocyte hyperplasia. Altogether, we establish a model of regulatory networks regulating adipose homeostasis in sheep tails. These findings improve our understanding of how adipose homeostasis is maintained, in response to extreme environments in animals.

Genomic analyses of Asiatic Mouflon in Iran provide insights into the domestication and evolution of sheep

“…We also found introgression signals in the PCDH9 (Figure 5E), which had been reported to be associated with local adaptation (e.g., hot and arid environments) in sheep and goats 69,70 , and fat deposition 71 . Also, early studies showed adipogenesis, ECM remodeling, inflammation, and lipid droplet dynamics in mature adipose tissue played essential roles in response to climate changes in sheep 72 . Further analysis from Chip-seq and RNA-Seq data will be required to uncover the function and regulatory mechanisms of PCDH9 to adapt to hot and humid environments in sheep.…”

“…These results implied that the AI region may regulate the function of PCDH9 . Also, early studies showed adipogenesis, ECM remodeling, inflammation, and lipid droplet dynamics in mature adipose tissue played essential roles in response to climate changes in sheep [73]. Further analysis from Chip-seq and RNA-Seq data will be required to uncover the function and regulatory mechanisms of PCDH9 to adapt to hot and humid environments in sheep.…”

Integration of selective sweeps across the sheep genome: understanding the relationship between production and adaptation traits

“…In livestock species, variants in the ADIPOQ gene are associated with marbling [ 102 , 103 ], body measurements [ 104 , 105 ], and growth and carcass traits [ 106 ]. It is crucial to recall that lipid metabolism plays an important role in sheep adaptation to extreme environments [ 107 ]. In addition, seasonality and adiposity in the body are associated; for instance, seasonal changes in body weight and fat percentage are observed frequently [ 108 ].…”

Genomic Landscape of Copy Number Variations and Their Associations with Climatic Variables in the World’s Sheep

“…CNV harboring functional candidate gene ( OAS2 ) with a high Wald score was associated with fat deposition in sheep breeds [ 68 ]. The tail fat might benefit adaptation to extreme environments and harsh seasons [ 69 ]. These results suggested that the genes with different numbers of copies are under climate-mediated selective pressures.…”