title: Beta-globin gene evolution in the ruminants: evidence for an ancient origin of sheep haplotype B.
abstract: Domestic sheep (Ovis aries) can be divided into two groups with significantly different responses to hypoxic environments, determined by two allelic beta-globin haplotypes. Haplotype A is very similar to the goat beta-globin locus, whereas haplotype B has a deletion spanning four globin genes, including beta-C globin, which encodes a globin with high oxygen affinity. We surveyed the beta-globin locus using resequencing data from 70 domestic sheep from 42 worldwide breeds and three Ovis canadensis and two Ovis dalli individuals. Haplotype B has an allele frequency of 71.4% in O. aries and was homozygous (BB) in all five wild sheep. This shared ancestry indicates haplotype B is at least 2-3 million years old. Approximately 40 kb of the sequence flanking the ~37-kb haplotype B deletion had unexpectedly low identity between haplotypes A and B. Phylogenetic analysis showed that the divergent region of sheep haplotype B is remarkably distinct from the beta-globin loci in goat and cattle but still groups with the Ruminantia. We hypothesize that this divergent ~40-kb region in haplotype B may be from an unknown ancestral ruminant and was maintained in the lineage to O. aries, but not other Bovidae, evolving independently of haplotype A. Alternatively, the ~40-kb sequence in haplotype B was more recently acquired by an ancestor of sheep from an unknown non-Bovidae ruminant, replacing part of haplotype A. Haplotype B has a lower nucleotide diversity than does haplotype A, suggesting a recent bottleneck, whereas the higher frequency of haplotype B suggests a subsequent spread through the global population of O. aries.
authors.affiliation: CSIRO Agriculture Flagship, St. Lucia, Qld, 4067, Australia.|College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: CSIRO Agriculture Flagship, St. Lucia, Qld, 4067, Australia.
authors.forename: J W
authors.initials: JW
authors.lastname: Kijas
authors.affiliation: CSIRO Agriculture Flagship, St. Lucia, Qld, 4067, Australia.
authors.forename: B P
authors.initials: BP
authors.lastname: Dalrymple
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D005787:Gene Frequency; D056426:Genetic Loci; D005828:Genetics, Population; D006239:Haplotypes; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D034561:Sheep, Domestic / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*
chemical_list: D055544:beta-Globins
keywords: Bos taurus; Capra hircus; Ovis aries; Pantholops hodgsonii; balancing selection; horizontal transfer; introgression; oxygen affinity