02565nas a2200277   4500000000100000008004100001260001200042653002400054653002200078653003900100653003400139653001700173653002200190653002100212653001400233100001300247700001500260700001300275700001500288245010900303856006800412300000900480490000700489520177700496022001402273       2023                            d  bMDPI AG10aInorganic Chemistry10aOrganic Chemistry10aPhysical and Theoretical Chemistry10aComputer Science Applications10aSpectroscopy10aMolecular Biology10aGeneral Medicine10aCatalysis1 aMatos MC1 aPinheiro A1 aDavis RS1 aEsteves PJ00aEvidence for Extensive Duplication and Subfunctionalization of FCRL6 in Armadillo (Dasypus novemcinctus)  uhttps://www.mdpi.com/1422-0067/24/5/4531/pdf?version=1677656817  a45310 v243 a<p>The control of infections by the vertebrate adaptive immune system requires careful modulation to optimize defense and minimize harm to the host. The Fc receptor-like (FCRL) genes encode immunoregulatory molecules homologous to the receptors for the Fc portion of immunoglobulin (FCR). To date, nine different genes (FCRL1–6, FCRLA, FCRLB and FCRLS) have been identified in mammalian organisms. FCRL6 is located at a separate chromosomal position from the FCRL1-5 locus, has conserved synteny in mammals and is situated between the SLAMF8 and DUSP23 genes. Here, we show that this three gene block underwent repeated duplication in Dasypus novemcinctus (nine-banded armadillo) resulting in six FCRL6 copies, of which five appear functional. Among 21 mammalian genomes analyzed, this expansion was unique to D. novemcinctus. Ig-like domains that derive from the five clustered FCRL6 functional gene copies show high structural conservation and sequence identity. However, the presence of multiple non-synonymous amino acid changes that would diversify individual receptor function has led to the hypothesis that FCRL6 endured subfunctionalization during evolution in D. novemcinctus. Interestingly, D. novemcinctus is noteworthy for its natural resistance to the Mycobacterium leprae pathogen that causes leprosy. Because FCRL6 is chiefly expressed by cytotoxic T and NK cells, which are important in cellular defense responses against M. leprae, we speculate that FCRL6 subfunctionalization could be relevant for the adaptation of D. novemcinctus to leprosy. These findings highlight the species-specific diversification of FCRL family members and the genetic complexity underlying evolving multigene families critical for modulating adaptive immune protection.</p>
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