Abstract

BackgroundNLRPs (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.ResultsBy 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.ConclusionIn 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).

Highlights

  • NLRPs (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing Proteins) are members of NLR (Nod-like receptors) protein family

  • We focus on the evolution and functional divergence of reproduction-related NLRPs, as well as lineage-specific expansion of Nlrp4 and Nlrp9 in rodents

  • By using Site-Models implemented in PAML4, we evaluated the variation of selective pressure acting on Nlrp4 and Nlrp9 duplicates, respectively

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Summary

Introduction

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 expressed in the oocyte in mammals. More and more researches have recently revealed that some NLRP genes play roles in mammalian reproduction. The mouse Nlrp (known as MATER) was one of the first identified mammalian maternal effect genes, i.e. it encodes mRNA required for successful development of a fertilized oocyte [8]. The recent expression analyses of NLRP genes in the human and the rhesus macaque (Macaca mulatta) have shown that most if not all NLRP genes are expressed in primate gametes and early embryos, suggesting a role of NLRPs in primate preimplantation development [15,16]

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