The most significant KEGG pathway in river buffaloes was the ‘ubiquitin-mediated proteolysis’ (P = 6.20E-04) (Fig. 3C, Supplementary Table 25 and Supplementary Fig. 32) and we found that six genes (HERC1, RFWD2, SKP1, UBR5, HERC4, CUL5) had functions regulating the ubiquitination and degradation of the misfolded proteins, which evoke neurotoxicity in many diseases like Alzheimer's and Parkinson's diseases [35]. Here, COP1 is linked to Parkinson disease.