AUTHOR=Matos Maria Carolina , Pinheiro Ana , Melo-Ferreira José , Davis Randall S. , Esteves Pedro José 

TITLE=Evolution of Fc Receptor-Like Scavenger in Mammals

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.590280

DOI=10.3389/fimmu.2020.590280

ISSN=1664-3224

ABSTRACT=<p>Fc receptor-like (FCRL) molecules comprise a large family of receptors, homologous to the receptors for the Fc portion of immunoglobulins (FCR). Within this family, an unusual gene known to exist in mice, rats and dogs, termed <italic>FCRLS</italic>, encodes a chimeric protein with both Ig-like FCRL and type B scavenger-receptor cysteine-rich (SRCR)-like domains. In mice, <italic>FCRLS</italic> is located next to the <italic>CD5L</italic> and <italic>KIRREL1</italic> genes. Here, we show that the curious <italic>FCRLS</italic> gene is actually present across major mammalian groups, but its annotation is generally incorrect or absent. Anchored on mouse <italic>FCRLS</italic> and <italic>FCRL2</italic> genomic sequence alignments, phylogenetic analyses demonstrated that many mammalian sequences currently annotated as <italic>FCRL2</italic> cluster with <italic>FCRLS</italic>, supported by a conserved genetic synteny among organisms. This analysis shows that <italic>FCRLS</italic> is present in Rodentia, some Carnivora (Canidae and Ursidae), Chiroptera, Arctiodactyla, Proboscidae, and some Primata. Thus, the <italic>FCRLS</italic> most likely originated in a eutherian mammal ancestor since it is not present in Monotremata or Marsupialia. <italic>FCRLS</italic> has a peculiar distribution pattern across mammalian lineages, being present in some species, but absent in others from the same family, as in carnivores for example. The most parsimonious hypothesis to explain this <italic>FCRLS</italic> evolution is that it was convergently lost in several independent mammalian lineages. Analyses of branch-specific nucleotide evolutionary rates, show that <italic>FCRL2</italic> and <italic>FCRLS</italic> have similar ranges of rates across mammals, suggesting that both genes have crucial, but separate functions in the immune system. Bayesian estimates of evolutionary rates for <italic>FCRLS</italic> in mammalian lineages revealed that carnivores display the highest mutation rate after rodents. Additionally, positive diversifying selection was detected for both <italic>FCRL2</italic> and <italic>FCRLS</italic>. Our results show that the presence of the <italic>FCRLS</italic> gene is older and more widespread across mammals than previously thought and appears to be functional, being under positive selection. Its precise physiologic role should thus be investigated.</p>