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The Evolution of Reproduction-Related NLRP Genes

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Abstract

NLRP proteins are important components of inflammasomes with a major role in innate immunity. A subset of NLRP genes, with unknown functions, are expressed in oocytes and early embryos. Mutations of Nlrp5 in mice are associated with maternal-effect embryonic lethality and mutations of NLRP7 in women are associated with conception of biparental complete hydatidiform moles (biCHMs), suggesting perturbed processes of genomic imprinting. Recessive mutations on NLRP2/7 in humans are associated with reproductive disorders and appear to be induced by a demethylation of the maternal pronucleus. In this study, we find that radiation of NLRP genes occurred before the common ancestor of Afrotheria and Boreoeutheria, with the clade of oocyte-expressed genes originating before the divergence of marsupial and eutherian mammals. There have been multiple independent duplications of NLRP2 genes one of which produced the NLRP7 gene associated with biCHMs.

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Correspondence to Edgar A. Duéñez-Guzmán.

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Supported by an Innovative Collaboration Award by the Howard Hughes Medical Institute to Catherine Dulac.

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239_2014_9614_MOESM1_ESM.pdf

Consensus phylogenetic tree of the NLRP gene family using Bayesian and maximumlikelihood methods. The support for the two methods is given as a pair of numbers between 0 (no support)and 1 (full support) for the Bayesian and maximum likelihood methods, respectively. These two valuesare separated by a vertical line character. A consensus cut-off threshold of 0:75 was used. Supportbelow the threshold is shown as an asterisk. (PDF 27 KB)

239_2014_9614_MOESM2_ESM.pdf

Table of all the sequences used in the analyses. The table contains the gene name,species of origin, chromosome location, NCBI accession number, and nucleotide position in the chromosome. (PDF 58 KB)

239_2014_9614_MOESM3_ESM.eps

Graphical depiction of NLRP genes and their flanking markers in all mammalianspecies used in this study. Genes are depicted as squares, chromosomes as vertical lines, and gene duplicationsand moves are depicted by arches. Genes are colored according to three categories. Non-NLRPgenes are gray, orthologs of human NLRP genes are cyan and gene duplications are colored yellow. (PS 144 KB)

Consensus phylogenetic tree of pig and human NLRP proteins as of May 2012. (PS 63 KB)

239_2014_9614_MOESM5_ESM.eps

Consensus phylogenetic tree of the NLRP gene family excluding reconstructed pseudogenes.The phylogenetic tree was inferred using MrBayes for 5,000,000 time steps, using the sameparameters as in Fig. 1. (PS 353 KB)

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Duéñez-Guzmán, E.A., Haig, D. The Evolution of Reproduction-Related NLRP Genes. J Mol Evol 78, 194–201 (2014). https://doi.org/10.1007/s00239-014-9614-3

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  • DOI: https://doi.org/10.1007/s00239-014-9614-3

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