Detecting the effects of selection at the population level in six bovine immune genes

BACKGROUND: The capacity of a species or population to respond to and survive novel infectious disease challenge is one of the most significant selective forces shaping genetic diversity and the period following animal domestication was likely one of the most important in terms of newly emerging diseases. Inter-specific genome-wide comparison has suggested that genes, including cluster of differentiation 2 (CD2), ADP-ribosyltransferase 4 (ART4), tyrosine kinase binding protein (TYROBP) and interleukins IL2, IL5, IL13, may have undergone positive selection during the evolution of the bovine lineage. Past adaptive change implies that more recent variation may have also been subject to selective forces. RESULTS: In this paper, we re-sequence each of these genes in cattle cohorts from Europe, Africa and Asia to investigate patterns of polymorphism at the population level. Patterns of diversity are higher within Bos indicus suggesting different demographic history to that of Bos taurus. Significant coding polymorphism was observed within each of the cell-surface receptors. In particular, CD2 shows two divergent haplotypes defined by a series of six derived nonsynonymous substitutions that are significantly clustered on the extracellular surface of the protein and give significant values for Fay and Wu's H, strongly suggesting a recent adaptive history. In contrast, the signaling molecules (especially IL13) display outlying allele frequency spectra which are consistent with the effects of selection, but display negligible coding polymorphism. CONCLUSION: We present evidence suggestive of recent adaptive history in bovine immune genes; implying some correspondence between intra- and inter-specific signals of selection. Interestingly, three signaling molecules have negligible nonsynonymous variation but show outlying test statistics in contrast to three receptors, where it is protein sequence diversity that suggests selective history.