Positive selection on two mitochondrial coding genes and adaptation signals in hares (genus Lepus) from China

Asma Awadi,Felix Knauer,Helmut Schaschl,Hichem Ben Slimen,Franz Suchentrunk

doi:10.1186/s12862-021-01832-7

Abstract

BackgroundAnimal mitochondria play a central role in energy production in the cells through the oxidative phosphorylation (OXPHOS) pathway. Recent studies of selection on different mitochondrial OXPHOS genes have revealed the adaptive implications of amino acid changes in these subunits. In hares, climatic variation and/or introgression were suggested to be at the origin of such adaptation. Here we looked for evidence of positive selection in three mitochondrial OXPHOS genes, using tests of selection, protein structure modelling and effects of amino acid substitutions on the protein function and stability. We also used statistical models to test for climate and introgression effects on sites under positive selection.ResultsOur results revealed seven sites under positive selection in ND4 and three sites in Cytb. However, no sites under positive selection were observed in the COX1 gene. All three subunits presented a high number of codons under negative selection. Sites under positive selection were mapped on the tridimensional structure of the predicted models for the respective mitochondrial subunit. Of the ten amino acid replacements inferred to have evolved under positive selection for both subunits, six were located in the transmembrane domain. On the other hand, three codons were identified as sites lining proton translocation channels. Furthermore, four codons were identified as destabilizing with a significant variation of Δ vibrational entropy energy between wild and mutant type. Moreover, our PROVEAN analysis suggested that among all positively selected sites two fixed amino acid replacements altered the protein functioning. Our statistical models indicated significant effects of climate on the presence of ND4 and Cytb protein variants, but no effect by trans-specific mitochondrial DNA introgression, which is not uncommon in a number of hare species.ConclusionsPositive selection was observed in several codons in two OXPHOS genes. We found that substitutions in the positively selected codons have structural and functional impacts on the encoded proteins. Our results are concordantly suggesting that adaptations have strongly affected the evolution of mtDNA of hare species with potential effects on the protein function. Environmental/climatic changes appear to be a major trigger of this adaptation, whereas trans-specific introgressive hybridization seems to play no major role for the occurrence of protein variants.

Highlights

Animal mitochondria play a central role in energy production in the cells through the oxidative phosphorylation (OXPHOS) pathway
These results suggested that the NADH dehydrogenase subunit 4 (ND4) gene was globally evolving under negative constraints, with a few percent of codons evolving under neutrality or positive selection
The CODEML analyses for Cytochrome oxidase 1 (COX1) showed that null models fitted better the data than models with positive selection indicating that this gene was evolving under neutrality

Summary

Introduction

Animal mitochondria play a central role in energy production in the cells through the oxidative phosphorylation (OXPHOS) pathway. The “mitochondrial climatic adaptation hypothesis” was often used to explain selection on mtDNA This hypothesis suggests that functional variation between mtDNA haplotypes plays an important role in shaping the genetic adaptation of populations to the temperatures of their environments [18]. The basis of this hypothesis is that mitochondrial genes encode multiple subunits in different enzyme complexes responsible for mitochondrial respiration, and these enzymatic processes are highly temperature sensitive [17]

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