Genomic signatures of selection in drug metabolizing genes across cattle populations

Abstract

Cattle are integral to agriculture and rural livelihoods in India, where diverse indigenous breeds have adapted to varied environments. The diversity of Indian breeds has shaped genetic traits linked to toxin processing, disease resistance, and metabolic efficiency. The genomic study of cattle reveals significant insights into the evolutionary pressures shaping drug-metabolizing genes (DMGs) across breeds. This study analyzed genome-wide selection signatures in seven cattle breeds, including Indigenous such as Red Sindhi (n = 96), Tharparkar (n = 72), Gir (n = 96), crossbred such as Frieswal (n = 14), Vrindavani (n = 72), and exotic cattle populations such as Holstein Friesian (n = 63), Jersey (n = 28). We utilized 50K and ddRAD SNP genotyping data to perform intra-population analyses (iHS, CLR, ROH) and inter-population analyses (F_ST, XP-EHH) for detecting genomic regions under selection. Key findings include the identification of cytochrome P450 genes (e.g., CYP7A1, CYP4A11, CYP19A1) and other DMGs exhibiting selection signatures linked to metabolic and biosynthetic processes. Red Sindhi cattle exhibited selection in genes like CYP7A1 and CYP2W1, which were involved in steroid biosynthesis and chemical stimulus response. Tharparkar cattle demonstrated positive selection in CYP4A11 and related genes involved in the functionalization of compounds. Crossbreeds of Vrindavani and Frieswal displayed intermediate signatures, reflecting mixed genetic contributions. Our research shows that Indigenous purebred cattle possess a superior selection signature of drug-metabolizing ability, enhanced disease resistance, and greater adaptability than crossbred and exotic breeds. This research contributes to understanding breed-specific adaptations, informing pharmacological interventions and conservation efforts.

Keywords: CYP; Cattle; Cytochrome 450; Drug metabolizing genes; Selection signature.