AUTHOR=Côrte-Real João Vasco , Baldauf Hanna-Mari , Melo-Ferreira José , Abrantes Joana , Esteves Pedro José 

TITLE=Evolution of Guanylate Binding Protein (GBP) Genes in Muroid Rodents (Muridae and Cricetidae) Reveals an Outstanding Pattern of Gain and Loss

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.752186

DOI=10.3389/fimmu.2022.752186

ISSN=1664-3224

ABSTRACT=<p>Guanylate binding proteins (GBPs) are paramount in the host immunity by providing defense against invading pathogens. Multigene families related to the immune system usually show that the duplicated genes can either undergo deletion, gain new functions, or become non-functional. Here, we show that in muroids, the <italic>Gbp</italic> genes followed an unusual pattern of gain and loss of genes. Muroids present a high diversity and plasticity regarding <italic>Gbp</italic> synteny, with most species presenting two <italic>Gbp</italic> gene clusters. The phylogenetic analyses revealed seven different <italic>Gbps</italic> groups. Three of them clustered with <italic>GBP2</italic>, <italic>GBP5</italic> and <italic>GBP6</italic> of primates. Four new <italic>Gbp</italic> genes that appear to be exclusive to muroids were identified as <italic>Gbpa</italic>, <italic>b</italic>, <italic>c</italic> and <italic>d</italic>. A duplication event occurred in the <italic>Gbpa</italic> group in the common ancestor of Muridae and Cricetidae (~20 Mya), but both copies were deleted from the genome of <italic>Mus musculus</italic>, <italic>M. caroli</italic> and <italic>Cricetulus griseus</italic>. The <italic>Gbpb</italic> gene emerged in the ancestor of Muridae and Cricetidae and evolved independently originating <italic>Gbpb1</italic> in Muridae, <italic>Gbpb2</italic> and <italic>Gbpb3</italic> in Cricetidae. Since <italic>Gbpc</italic> appears only in three species, we hypothesize that it was present in the common ancestor and deleted from most muroid genomes. The second <italic>Gbp</italic> gene cluster, <italic>Gbp6</italic>, is widespread across all muroids, indicating that this cluster emerged before the Muridae and Cricetidae radiation. An expansion of <italic>Gbp6</italic> occurred in <italic>M. musculus</italic> and <italic>M. caroli</italic> probably to compensate the loss of <italic>Gbpa</italic> and <italic>b</italic>. <italic>Gbpd</italic> is divided in three groups and is present in most muroids suggesting that a duplication event occurred in the common ancestor of Muridae and Cricetidae. However, in <italic>Grammomys surdaster</italic> and <italic>Mus caroli, Gbpd2</italic> is absent, and in <italic>Arvicanthis niloticus, Gbpd1</italic> appears to have been deleted. Our results further demonstrated that primate <italic>GBP1</italic>, <italic>GBP3</italic> and <italic>GBP7</italic> are absent from the genome of muroids and showed that the <italic>Gbp</italic> gene annotations in muroids were incorrect. We propose a new classification based on the phylogenetic analyses and the divergence between the groups. Extrapolations to humans based on functional studies of muroid <italic>Gbps</italic> should be re-evaluated. The evolutionary analyses of muroid <italic>Gbp</italic> genes provided new insights about the evolution and function of these genes.</p>