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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\u20136, 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.<\/jats:p>","DOI":"10.3390\/ijms24054531","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:23:36Z","timestamp":1677468216000},"page":"4531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evidence for Extensive Duplication and Subfunctionalization of FCRL6 in Armadillo (Dasypus novemcinctus)"],"prefix":"10.3390","volume":"24","author":[{"given":"Maria Carolina","family":"Matos","sequence":"first","affiliation":[{"name":"CIBIO-UP, Centro de Investiga\u00e7\u00e3o em Biodiversidade e Recursos Gen\u00e9ticos, InBIO Laborat\u00f3rio Associado, Campus Agr\u00e1rio de Vair\u00e3o, Universidade do Porto, 4485-661 Vair\u00e3o, Portugal"},{"name":"BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, 4485-661 Vair\u00e3o, Portugal"},{"name":"Departamento de Biologia, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"given":"Ana","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"CIBIO-UP, Centro de Investiga\u00e7\u00e3o em Biodiversidade e Recursos Gen\u00e9ticos, InBIO Laborat\u00f3rio Associado, Campus Agr\u00e1rio de Vair\u00e3o, Universidade do Porto, 4485-661 Vair\u00e3o, Portugal"},{"name":"BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, 4485-661 Vair\u00e3o, Portugal"}]},{"given":"Randall S.","family":"Davis","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Microbiology, and Biochemistry & Molecular Genetics, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-8298","authenticated-orcid":false,"given":"Pedro J.","family":"Esteves","sequence":"additional","affiliation":[{"name":"CIBIO-UP, Centro de Investiga\u00e7\u00e3o em Biodiversidade e Recursos Gen\u00e9ticos, InBIO Laborat\u00f3rio Associado, Campus Agr\u00e1rio de Vair\u00e3o, Universidade do Porto, 4485-661 Vair\u00e3o, Portugal"},{"name":"BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, 4485-661 Vair\u00e3o, Portugal"},{"name":"Departamento de Biologia, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"},{"name":"CITS-Centro de Investiga\u00e7\u00e3o em Tecnologias de Sa\u00fade, Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio, CRL (CESPU), 4585-116 Gandra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ahmed, R., and Honjo, T. 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