Divergent evolution in the cytoplasmic domains of PRLR and GHR genes in Artiodactyla

Abstract

Background: Prolactin receptor (PRLR) and growth hormone receptor (GHR) belong to the large superfamily of class 1 cytokine receptors. Both of them have been identified as candidate genes affecting key quantitative traits, like growth and reproduction in livestock. We have previously studied the molecular anatomy of the cytoplasmic domain of GHR in different cattle breeds and artiodactyl species. In this study we have analysed the corresponding cytoplasmic signalling region of PRLR.

Results: We sequenced PRLR gene exon 10, coding for the major part of the cytoplasmic domain, from cattle, American bison, European bison, yak, sheep, pig and wild boar individuals. We found different patterns of variation in the two receptors within and between ruminants and pigs. Pigs and bison species have no variation within GHR exon 10, but show high haplotype diversity for the PRLR exon 10. In cattle, PRLR shows lower diversity than GHR. The Bovinae PRLR haplotype network fits better the known phylogenetic relationships between the species than that of the GHR, where differences within cattle breeds are larger than between the different species in the subfamily. By comparison with the wild boar haplotypes, a high number of subsequent nonsynonymous substitutions seem to have accumulated in the pig PRLR exon 10 after domestication.

Conclusion: Both genes affect a multitude of traits that have been targets of selection after domestication. The genes seem to have responded differently to different selection pressures imposed by human artificial selection. The results suggest possible effects of selective sweeps in GHR before domestication in the pig lineage or species divergence in the Bison lineage. The PRLR results may be explained by strong directional selection in pigs or functional switching.

Figure 1

Statistically inferred cattle, yak, American bison and European bison haplotypes from the PRLR exon 10. Only variable sites are shown. SNP numbering is based on the sequence NM_001039726.1. Amino acid numbering starts from the first methionine in the protein sequence NP_001034815.1.

Figure 2

Statistically inferred sheep haplotypes from the PRLR exon 10.

Figure 3

Statistically inferred pig haplotypes from the PRLR exon 10.

Figure 4

Sliding window presentation of the nucleotide divergence along PRLR exon 10 among 18 different species. Bta = cattle, Bbi = American bison, Bbo = European bison, Ovis = sheep, Sus = pig. The positions of the detected SNPs are shown on the X-axis.

Figure 5

Parsimony network reconstructions. a) Bovinae haplotype network. Different colours represent different cattle breed groups and/or species. b) Ovis haplotype network c) Sus haplotype network. The size of the pie is proportional to the frequency of the haplotype for the breed group in question and the size of the node area is proportional to the total frequency of the haplotype in the whole population. Small black circles represent the hypothetical haplotypes not present in this study. BOS = cattle, Bbi = American bison, Bbo = European bison, BOSgr = yak, SUS = pig, OVIS = sheep.