Evolution of CCR5 and CCR2 Genes in Bats Showed Multiple Independent Gene Conversion Events.

Pedro J. Esteves,Ana Águeda-Pinto,Ana Pinheiro,Alexandre P. Fernandes,Hugo Rebelo

doi:10.3390/v14020169

Abstract

Chemokine receptors are an important determinant for the infectiousness of different pathogens, which are able to target the host cells by binding to the extracellular domains of these proteins. This is the mechanism of infection of HIV-1, among other concerning human diseases. Over the past years, it has been shown that two chemokine receptors, CCR2 and CCR5, have been shaped by events of gene conversion in different mammalian lineages, which has been linked to a possible selective advantage against pathogens. Here, by taking advantage of available bat genomes, we present the first insight of CCR2 and CCR5 evolution within the Chiroptera order. In total, four independent events of recombination between CCR2 and CCR5 were detected: two in a single species, Miniopterus natalensis; one in two species from the Rhinolophoidea superfamily; and one in four species from the Pteropodidae family. The regions affected by the gene conversions were generally extensive and always encompassed extracellular domains. Overall, we demonstrate that CCR2 and CCR5 have been subject to extensive gene conversion in multiple species of bats. Considering that bats are known to be large reservoirs of virus in nature, these results might indicate that chimeric CCR2-CCR5 genes might grant some bat species a selective advantage against viruses that rely in the extracellular portions of either CCR2 or CCR5 as gateways into the cell.

Highlights

Chemokine receptors are a family of seven-transmembrane-spanning G proteins important to immunological pathway signaling due to their binding ability with chemokines
The coding DNA sequences (CDSs) of CCR2 and CCR5 genes from 18 bat species were manually extracted from the NCBI database
Our main goal was to determine whether the CCR2 and CCR5 genes of bats were affected by gene conversion during their evolutionary history

Summary

Introduction

Chemokine receptors are a family of seven-transmembrane-spanning G proteins important to immunological pathway signaling due to their binding ability with chemokines. Two hypotheses have been put forward as possible explanations for the fixation of chimeric CCR2-CCR5 genes in different orders of mammals: (i) they facilitate the formation of CCR2-CCR5 heterodimers, which have been shown to naturally occur in human cells [14]; or (ii) they provide a selective advantage against viruses which may have used either CCR5 or CCR2 as gateways to enter the cell (in a similar fashion to HIV-1 in humans) [15,16,17] Such CCR2-CCR5 recombinants have been reported in rodent, feline, leporid, guinea pig, horse, pig, marsupial, and primate lineages [14,15,16,17,18,19]. We investigate possible events of gene conversion happening in CCR2 and CCR5 genes from different bat species, which may pave the way to further clarify their immune system function on these mammals

Data Retrieval

Detection of Recombination and Phylogenetic Analysis

Results and Discussion