Title: Adaptive Divergence in the Bovine Genome 1 2

21 Cattle diverged during the Pleistocene into two subspecies, one in temperate and one in 22 tropical environments. Here we have used next generation sequencing of the indicine 23 subspecies of cattle and compared it to the taurine subspecies. Although 23.8 million 24 single nucleotide polymorphisms (SNP) were found, the number of fixed amino acid 25 substitutions between the taurine and indicine subspecies was low and consistent with the 26 Haldane predictions for adaptive selection rather than with Neutral Theory. We noted 33 27 regions of enhanced divergence of nonsynonymous SNP between the subspecies, which 28 included an increased rate of deleterious variants. Signals of positive selection were found 29 for genes associated with immunity, including the Bovine Major Histocompatibility 30 Complex, which also showed an increased rate of deleterious amino acid variants. The 31 genes important in sensing the environment, especially the olfactory system, showed a 32 network wide signal of positive selection. 33 34 2 Introduction 38 39 Cattle are a rare example of adaptive divergence into temperate and tropical environments 40 in which the subspecies show hybrid vigour on being crossed. Genome wide analyses of 41 evolution in cattle have focussed on the expansion of gene families or on evidence of 42 selection signatures using population genetic evidence based on genotype or haplotype 43 frequencies, mainly in the taurine subspecies. The initial sequencing of cattle found gene 44 families that were expanded in cattle lineages, identifying genes associated with the 45 immune system in particular that were increased in number compared to other mammalian 46 species (Elsik et al. 2009). In addition, analyses of genotype or haplotype frequencies have 47 been used to identify signatures of selection and in some cases have linked these to the 48 known locations of quantitative trait loci (Barendse et al. Analyses of nonsynonymous and synonymous DNA variants 50 have been performed for a limited number of amplicons for genes expected to be involved 51 in animal production (MacEachern et al. 2009b). 52 53 The description of the genomic variation and structure of the indicus subspecies lags 54 behind that of the taurus subspecies of cattle. The taurine subspecies is of temperate origin 55 while the indicine subspecies is of tropical origin. Individuals of several of the breeds of 56 taurine cattle, 61 sequencing studies have documented variation, not only at the single nucleotide 62 polymorphism (SNP) level, but also structural variation …