CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, InBIO Laboratório Associado, Campus Agrário de Vairão, Universidade do Porto, 4485-661 Vairão, Portugal.
BIOPOLIS Program in Genomics, Biodiversity and Land Planning, CIBIO, 4485-661 Vairão, Portugal.
Int J Mol Sci. 2023 Feb 25;24(5):4531. doi: 10.3390/ijms24054531.
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 () genes encode immunoregulatory molecules homologous to the receptors for the Fc portion of immunoglobulin (FCR). To date, nine different genes (, , and ) have been identified in mammalian organisms. is located at a separate chromosomal position from the locus, has conserved synteny in mammals and is situated between the and genes. Here, we show that this three gene block underwent repeated duplication in (nine-banded armadillo) resulting in six copies, of which five appear functional. Among 21 mammalian genomes analyzed, this expansion was unique to . Ig-like domains that derive from the five clustered 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 endured subfunctionalization during evolution in . Interestingly, is noteworthy for its natural resistance to the pathogen that causes leprosy. Because is chiefly expressed by cytotoxic T and NK cells, which are important in cellular defense responses against , we speculate that subfunctionalization could be relevant for the adaptation of to leprosy. These findings highlight the species-specific diversification of family members and the genetic complexity underlying evolving multigene families critical for modulating adaptive immune protection.
脊椎动物适应性免疫系统通过精细的调控来控制感染,以优化防御并最小化对宿主的伤害。Fc 受体样()基因编码与免疫球蛋白(FCR)Fc 部分的受体同源的免疫调节分子。迄今为止,已在哺乳动物中鉴定出九个不同的基因(、、和)。位于与基因座分离的染色体位置,在哺乳动物中有保守的同线性,位于和基因之间。在这里,我们表明这个三基因块在(九带犰狳)中经历了重复复制,导致六个拷贝,其中五个似乎是功能性的。在分析的 21 种哺乳动物基因组中,这种扩张是独特的。源自五个聚集的功能基因拷贝的 Ig 样结构域显示出高度的结构保守性和序列同一性。然而,存在多个非同义氨基酸变化,这些变化会使个体受体功能多样化,这导致了这样的假说,即在进化过程中,发生了亚功能化。有趣的是,值得注意的是,它对引起麻风病的病原体具有天然抗性。因为主要由细胞毒性 T 和 NK 细胞表达,这些细胞在针对的细胞防御反应中很重要,我们推测在进化过程中,的亚功能化可能与对麻风病的适应有关。这些发现强调了家族成员的物种特异性多样化以及对调节适应性免疫保护至关重要的多基因家族进化的遗传复杂性。