Genetic variation in the major histocompatibility complex of the European brown hare (Lepus europaeus) across distinct phylogeographic areas

Abstract

The major histocompatibility complex is one of the best studied systems in vertebrates providing evidence for the long-term action of selection. Here, we examined the intra- and inter-population genetic diversity of the MHC class II DRB locus in European brown hare (Lepus europaeus) and correlated the results with genetic variability already estimated from the MHC DQA locus and from maternally (mitochondrial DNA (mtDNA)) and biparentally (allozymes, microsatellites) inherited loci. L. europaeus showed remarkable genetic polymorphism in both DQA and DRB1 loci. The Anatolian populations exhibited the highest genetic polymorphism for both loci. Balancing selection has established increased variability in the European populations despite the founder effects after the last glaciation. Different evolutionary rates were traced for DRB1 and DQA loci, as evidenced by the higher number of common DRB1 than DQA alleles and the greater differences between DRB1 alleles with common origin in comparison with DQA alleles. The high number of rare alleles with low frequencies detected implies that frequency-dependent selection drives MHC evolution in the brown hare through the advantage of rare alleles. Both loci were under the influence of positive selection within the peptide-binding region. The functional polymorphism, recorded as amino acid substitutions within the binding pockets, fell also within distinct geographic patterns, yet it was much narrower than the genetic polymorphism. We hypothesize that certain structural and functional characteristics of the binding pockets set limitations to the actual shape of genetic polymorphism in MHC.

Lepus europaeus(Lagomorpha: Leporidae)

“…There is a high and stable genetic polymorphism due to balancing selection and a significant difference between Anatolian and European populations with the Anatolian population exhibiting the highest genetic polymorphism for both loci. Functional polymorphism of the binding pockets also revealed the existence of distinct geographic patterns (Koutsogiannouli et al 2014).…”

“…The genetic variability of L. europaeus in its native range, including European and Anatolian regions was investigated by Koutsogiannouli et al (2014) who studied 80 L. europaeus from 16 geographically different populations, classified into four phylogeographic groups. Data were analyzed with regard to genetic polymorphism in the MHC (major histocompatibility complex) particularly DQA and DRB1 loci and functional polymorphism in binding pockets (amino acid substitutions).…”