Tian Xin, Pascal Géraldine, Monget Philippe
Physiologie de la Reproduction et des Comportements, UMR 6175 INRA-CNRS-Université François Rabelais de Tours-Haras Nationaux, 37380 Nouzilly, France.
BMC Evol Biol. 2009 Aug 14;9:202. doi: 10.1186/1471-2148-9-202.
NLRPs (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing Proteins) are members of NLR (Nod-like receptors) protein family. Recent researches have shown that NLRP genes play important roles in both mammalian innate immune system and reproductive system. Several of NLRP genes were shown to be specifically expressed in the oocyte in mammals. The aim of the present work was to study how these genes evolved and diverged after their duplication, as well as whether natural selection played a role during their evolution.
By using in silico methods, we have evaluated the evolution and functional divergence of NLRP genes, in particular of mouse reproduction-related Nlrp genes. We found that (1) major NLRP genes have been duplicated before the divergence of mammals, with certain lineage-specific duplications in primates (NLRP7 and 11) and in rodents (Nlrp1, 4 and 9 duplicates); (2) tandem duplication events gave rise to a mammalian reproduction-related NLRP cluster including NLRP2, 4, 5, 7, 8, 9, 11, 13 and 14 genes; (3) the function of mammalian oocyte-specific NLRP genes (NLRP4, 5, 9 and 14) might have diverged during gene evolution; (4) recent segmental duplications concerning Nlrp4 copies and vomeronasal 1 receptor encoding genes (V1r) have been undertaken in the mouse; and (5) duplicates of Nlrp4 and 9 in the mouse might have been subjected to adaptive evolution.
In conclusion, this study brings us novel information on the evolution of mammalian reproduction-related NLRPs. On the one hand, NLRP genes duplicated and functionally diversified in mammalian reproductive systems (such as NLRP4, 5, 9 and 14). On the other hand, during evolution, different lineages adapted to develop their own NLRP genes, particularly in reproductive function (such as the specific expansion of Nlrp4 and Nlrp9 in the mouse).
NLRP（含核苷酸结合寡聚化结构域、富含亮氨酸重复序列和吡啉结构域的蛋白质）是NLR（Nod样受体）蛋白家族的成员。最近的研究表明，NLRP基因在哺乳动物的先天免疫系统和生殖系统中都发挥着重要作用。有几种NLRP基因在哺乳动物的卵母细胞中特异性表达。本研究的目的是研究这些基因在复制后是如何进化和分化的，以及自然选择在其进化过程中是否发挥了作用。
通过计算机模拟方法，我们评估了NLRP基因的进化和功能分化，特别是与小鼠繁殖相关的Nlrp基因。我们发现：（1）主要的NLRP基因在哺乳动物分化之前就已经复制，在灵长类动物（NLRP7和11）和啮齿动物（Nlrp1、4和9的复制）中存在特定的谱系特异性复制；（2）串联复制事件产生了一个与哺乳动物繁殖相关的NLRP簇，包括NLRP2、4、5、7、8、9、11、13和14基因；（3）哺乳动物卵母细胞特异性NLRP基因（NLRP4、5、9和14）的功能可能在基因进化过程中发生了分化；（4）小鼠中发生了与Nlrp4拷贝和犁鼻器1受体编码基因（V1r）相关的近期片段重复；（5）小鼠中Nlrp4和9的复制可能经历了适应性进化。
总之，本研究为哺乳动物繁殖相关NLRP的进化带来了新的信息。一方面，NLRP基因在哺乳动物生殖系统中复制并功能多样化（如NLRP4、5、9和14）。另一方面，在进化过程中，不同的谱系适应发展出自己的NLRP基因，特别是在生殖功能方面（如小鼠中Nlrp4和Nlrp9的特异性扩增）。
