Genetic diversity of BoLA-DRB3 in South American Zebu cattle populations

Shin-nosuke Takeshima, Claudia Corbi-Botto, Guillermo Giovambattista, Yoko Aida

Bovine leukocyte antigens (BoLAs) are used extensively as markers of disease and immunological traits in cattle. However, until now, characterization of BoLA gene polymorphisms in Zebu breeds using high resolution typing methods has been poor. Here, we used a polymerase chain reaction sequence-based typing (PCR-SBT) method to sequence exon 2 of the BoLA class II DRB3 gene from 421 cattle (116 Bolivian Nellore, 110 Bolivian Gir, and 195 Peruvian Nellore-Brahman). Data from 1416 Taurine and Zebu samples were also included in the analysis. We identified 46 previously reported alleles and no novel variants. Of note, 1/3 of the alleles were detected only in Zebu cattle. Comparison of the degree of genetic variability at the population and sequence levels with genetic distance in the three above mentioned breeds and nine previously reported breeds revealed that Zebu breeds had a gene diversity score higher than 0.86, a nucleotide diversity score higher than 0.06, and a mean number of pairwise differences greater than 16, being similar to those estimated for other cattle breeds. A neutrality test revealed that only Nellore-Brahman cattle showed the even gene frequency distribution expected under a balanced selection scenario. The FST index and the exact G test showed significant differences across all cattle populations (FST = 0.057; p <  0.001). Neighbor-joining trees and principal component analysis identified two major clusters: one comprising mainly European Taurine breeds and a second comprising Zebu breeds. This is consistent with the historical and geographical origin of these breeds. Some of these differences may be explained by variation of amino acid motifs at antigen-binding sites. The results presented herein show that the historical divergence between Taurine and Zebu cattle breeds is a result of origin, selection, and adaptation events, which would explain the observed differences in BoLA-DRB3 gene diversity between the two major bovine types. This allelic information will be important for investigating the relationship between the major histocompatibility complex and disease, and contribute to an ongoing effort to catalog bovine MHC allele frequencies according to breed and location.