Evolution and functional divergence of NLRPgenes in mammalian reproductive systems

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).

Generation and Characterization of a Novel Cyp2a(4/5)bgs-Null Mouse Model

“…Our finding that Cyp2a(4/5)bgs-null mice are viable and fertile indicates that these five non-Cyp genes are not critical for embryonic or postnatal development or for reproduction. The Nalp4 and Nalp9 (also named Nlrp4 and Nlrp9) genes are members of the NLRP (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing proteins) gene family (Tian et al, 2009), which are mainly expressed in oocytes and embryos in early developmental stages. The availability of the Cyp2a(4/5)bgs-null mouse, as a Nlrp9c-4a-9a knockout mouse, may be helpful for studies on potential compensatory mechanisms in the oocyte, and on other potential biologic functions of these proteins.…”

The human RBPome: From genes and proteins to human disease

“…Genes in this group included DCD-an antimicrobial peptide coding gene, member of the APOBEC family which are specific to primates and mammals [54]. Furthermore, nLRP11 -a member of the Nod-like receptor protein family was observed to be present only in mammals [55]. Analysis of the variations in the extent of conservation between classical and nonclassical RBPs across species showed that there is no significant difference (p=0.1, Fishers exact test)( Figure 3E).…”

Expression patterns of Nlrp9a, Nlrp9b and Nlrp9c during mouse development

“…Because three Nlrp genes show lineage-specific duplications including Nlrp1 (Nlrp1a, Nlrp1b and Nlrp1c), Nlrp4 (Nlrp4a-Nlrp4g) and Nlrp9 (Nlrp9a, Nlrp9b and Nlrp9c), meanwhile, Nlrp7, Nlrp8, Nlrp11 and Nlrp13 are lost in the mouse. The phylogenetic analyses identified a well supported reproduction-related clade including nine NLRP proteins (NLRP2,4,5,7,8,9,11,13 and 14) in humans (Tian et al 2009). In the reproduction-related NLRP cluster, there are several oocyte-specific NLRP genes including NLRP2, 4, 5, 8, 9 and 14 (Tian et al 2009).…”

“…The phylogenetic analyses identified a well supported reproduction-related clade including nine NLRP proteins (NLRP2,4,5,7,8,9,11,13 and 14) in humans (Tian et al 2009). In the reproduction-related NLRP cluster, there are several oocyte-specific NLRP genes including NLRP2, 4, 5, 8, 9 and 14 (Tian et al 2009). …”