Evolutionary Dynamics of the Casein Gene Family in Goat and Sheep: In-Silico Analysis of Structural, Functional and Regulatory Signatures

Abstract

Caseins, the primary milk proteins in ruminants, critically influence dairy quality and functionality, yet their evolutionary and regulatory divergence between goats (Capra hircus) and sheep (Ovis aries) remains unresolved. Here, we performed the first comparative genomics analysis of the casein gene family (CSN1S1, CSN1S2, CSN2, CSN3) in these species, integrating phylogenetics, promoter profiling and structural biology. Phylogenetic reconstruction confirmed shared ancestry between goats and sheep, with CSN1S1 and CSN2 clustering into distinct clades (bootstrap >85%). Caseins exhibited intrinsic disorder (39-72% disordered regions) and hydrophilicity (GRAVY <0), yet goats showed enhanced thermal resilience (aliphatic index >100 for CSN2), a likely adaptation to heat stress. Promoter analysis revealed goats elevated CSN1S2 and CSN2 activity scores and reduced YY1 repressor sites compared to sheep, which is novel regulatory divergence potentially enhancing lactation efficiency. These findings provide a genomic blueprint for optimizing milk traits in small ruminants, offering actionable targets for precision breeding in tropical agricultural economics.