Evolutionary genetics of MHC class II beta genes in the brown hare, Lepus europaeus

Abstract

The genes of the major histocompatibility complex (MHC) are attractive candidates for investigating the link between adaptive variation and individual fitness. High levels of diversity at the MHC are thought to be the result of parasite-mediated selection and there is growing evidence to support this theory. Most studies, however, target just a single gene within the MHC and infer any evidence of selection to be representative of the entire gene region. Here we present data from three MHC class II beta genes (DPB, DQB, and DRB) for brown hares in two geographic regions and compare them against previous results from a class II alpha-chain gene (DQA). We report moderate levels of diversity and high levels of population differentiation in the DQB and DRB genes (Na = 11, D (est) = 0.071 and Na = 15, D (est) = 0.409, respectively), but not for the DPB gene (Na = 4, D (est) = 0.00). We also detected evidence of positive selection within the peptide binding region of the DQB and DRB genes (95% CI, ω > 1.0) but found no signature of selection for DPB. Mutation and recombination were both found to be important processes shaping the evolution of the class II genes. Our findings suggest that while diversifying selection is a significant contributor to the generally high levels of MHC diversity, it does not act in a uniform manner across the entire MHC class II region. The beta-chain genes that we have characterized provide a valuable set of MHC class II markers for future studies of the evolution of adaptive variation in Leporids.

Fig. 1

Sampling localities of brown hares from Belgium (hatched circles) and Austria (stars). BK Bulskamp, SL Sint Laureins, MB Moerbeke, OW/STR Oberweiden/Stripfing, ZW Zwerndorf, BG/LA Baumgarten/Lassee

Fig. 2

Omega Plot output for a the DQB gene and b the DRB gene. The dotted line indicates omega (ω) = 1. The unbroken line shows the mean value for ω from posterior distribution, and the shadowed area displays the 95% confidence interval. Amino acid codes are shown above each plot, and those presumed to be involved in peptide binding based on the human sequence are in bold. Codon positions are given with respect to the standard human HLA numbering and are considered to be significantly under the influence of positive selection if the mean and 95% confidence interval for ω > 1. Positively selected sites for DQB are 26S and 60 N and for DRB are 11 V, 57I, 67 L, 71R, 74S, and 78Y. All positively selected sites correspond to proposed peptide-binding regions