Positive selection and climatic effects on MHC class II gene diversity in hares (Lepus capensis) from a steep ecological gradient

Asma Awadi,Franz Suchentrunk,Felix Knauer,Steve Smith,Hichem Ben Slimen,Mohamed Makni

doi:10.1038/s41598-018-29657-3

Abstract

In natural populations, allelic diversity of the major histocompatibility complex (MHC) is commonly interpreted as resulting from positive selection in varying spatiotemporal pathogenic landscapes. Composite pathogenic landscape data are, however, rarely available. We studied the spatial distribution of allelic diversity at two MHC class II loci (DQA, DQB) in hares, Lepus capensis, along a steep ecological gradient in North Africa and tested the role of climatic parameters for the spatial distribution of DQA and DQB proteins. Climatic parameters were considered to reflect to some extent pathogenic landscape variation. We investigated historical and contemporary forces that have shaped the variability at both genes, and tested for differential selective pressure across the ecological gradient by comparing allelic variation at MHC and neutral loci. We found positive selection on both MHC loci and significantly decreasing diversity from North to South Tunisia. Our multinomial linear models revealed significant effects of geographical positions that were correlated with mean annual temperature and precipitation on the occurrence of protein variants, but no effects of co-occurring DQA or DQB proteins, respectively. Diversifying selection, recombination, adaptation to local pathogenic landscapes (supposedly reflected by climate parameters) and neutral demographic processes have shaped the observed MHC diversity and differentiation patterns.

Highlights

Genetic studies of natural populations based on presumably neutral markers such as mitochondrial d-loop DNA, microsatellites or SNPs are important to infer phylogeny, population history and gene flow[1,2]
Adaptation to local or regional pathogenic landscapes is often addressed by analyses of major histocompatibility genes (MHC) which code for glycoproteins that recognize and bind antigens in order to present them to CD4+ and CD8+T-lymphocytes to initiate the adaptive immune response against pathogens
We expect that major histocompatibility complex (MHC) diversity varies significantly between the regional populations under study given that spatial changes in parasite communities and dynamics with environmental conditions might alter the selection pressures they exert on their host populations[17]

Summary

Introduction

Genetic studies of natural populations based on presumably neutral markers such as mitochondrial d-loop DNA (mtDNA), microsatellites or SNPs are important to infer phylogeny, population history and gene flow[1,2]. A study of Tunisian hare populations indicated a strong population structure at mitochondrial OXPHOS genes, which are under positive selection at several codons, despite a high gene flow at neutral markers[5] These findings are consistent with local adaptation according to climate variation[5]. These domains are highly polymorphic and are encoded by the second exon of A and B MHCII genes Given their role in presenting antigenic determinant peptides to the cell surface, these loci are typically expected to be subject to strong positive selection, since their greater allelic diversity should be associated with a response to a wider range of pathogens[16]. Neutral demographic processes (i.e., gene flow, genetic drift...) can have significant effects on the genetic diversity of natural populations[4,34]

Methods

Results

Conclusion