The assembly and characterisation of two structurally distinct cattle MHC class I haplotypes point to the mechanisms driving diversity.

John C Schwartz,John A Hammond

doi:10.1007/s00251-015-0859-9

Abstract

In cattle, there are six classical MHC class I genes that are variably present between different haplotypes. Almost all known haplotypes contain between one and three genes, with an allele of Gene 2 present on the vast majority. However, very little is known about the sequence and therefore structure and evolutionary history of this genomic region. To address this, we have refined the MHC class I region in the Hereford cattle genome assembly and sequenced a complete A14 haplotype from a homozygous Holstein. Comparison of the two haplotypes revealed extensive variation within the MHC class Ia region, but not within the flanking regions, with each gene contained within a conserved 63- to 68-kb sequence block. This variable region appears to have undergone block gene duplication and likely deletion at regular breakpoints, suggestive of a site-specific mechanism. Phylogenetic analysis using complete gene sequences provided evidence of allelic diversification via gene conversion, with breakpoints between each of the extracellular domains that were associated with high guanine-cytosine (GC) content. Advancing our knowledge of cattle MHC class I evolution will help inform investigations of cattle genetic diversity and disease resistance.

Highlights

In cattle, there are six classical Major histocompatibility complex (MHC) class I genes that are variably present between different haplotypes
As well as allelic polymorphism, cattle MHC class I haplotypes vary in gene content; only one to three of these genes are present on any given haplotype, with Gene 2 being the most ubiquitous (Birch et al 2006; Codner et al 2012; Ellis et al 1999)
The allelic diversity of Holstein cattle MHC class I has been well studied; very little is known about the full gene sequences and underlying genomic structure between the numerous different haplotypes

Summary

Introduction

There are six classical MHC class I genes that are variably present between different haplotypes. The allelic diversity of Holstein cattle MHC class I has been well studied; very little is known about the full gene sequences and underlying genomic structure between the numerous different haplotypes.

Results

Conclusion