Eutherian-Specific Gene TRIML2 Attenuates Inflammation in the Evolution of Placentation.

Xuzhe Zhang,Mihaela Pavlicev,Helen N Jones,Louis J Muglia,Yoko Satta

doi:10.1093/molbev/msz238

Abstract

Evolution of highly invasive placentation in the stem lineage of eutherians and subsequent extension of pregnancy set eutherians apart from other mammals, that is, marsupials with short-lived placentas, and oviparous monotremes. Recent studies suggest that eutherian implantation evolved from marsupial attachment reaction, an inflammatory process induced by the direct contact of fetal placenta with maternal endometrium after the breakdown of the shell coat, and shortly before the onset of parturition. Unique to eutherians, a dramatic downregulation of inflammation after implantation prevents the onset of premature parturition, and is critical for the maintenance of gestation. This downregulation likely involved evolutionary changes on maternal as well as fetal/placental side. Tripartite-motif family-like2 (TRIML2) only exists in eutherian genomes and shows preferential expression in preimplantation embryos, and trophoblast-derived structures, such as chorion and placental disc. Comparative genomic evidence supports that TRIML2 originated from a gene duplication event in the stem lineage of Eutheria that also gave rise to eutherian TRIML1. Compared with TRIML1, TRIML2 lost the catalytic RING domain of E3 ligase. However, only TRIML2 is induced in human choriocarcinoma cell line JEG3 with poly(I:C) treatment to simulate inflammation during viral infection. Its knockdown increases the production of proinflammatory cytokines and reduces trophoblast survival during poly(I:C) stimulation, while its overexpression reduces proinflammatory cytokine production, supporting TRIML2’s role as a regulatory inhibitor of the inflammatory pathways in trophoblasts. TRIML2’s potential virus-interacting PRY/SPRY domain shows significant signature of selection, suggesting its contribution to the evolution of eutherian-specific inflammation regulation during placentation.

Highlights

Gene duplication is one of the most common approaches for new gene to emerge
The paradox between the high incidence of preterm birth seen in human, and its significant reproduction/survival disadvantage may point to the constrains over the evolution of reproduction mode, which unavoidably involves the modification of pleotropic preexisting pathways, as well as the competition of interests, such as the trade-off between mother and the offspring, and the arms race between host and infectious pathogens
As many tripartite motif (TRIM), especially vertebrate-specific group-2 TRIMs, exist in spatial gene clusters (Versteeg et al 2014), we scanned for TRIM clusters that exist in all four representative species of extant eutherian superorders though UCSC genome browser, and found that TRIML1 and Tripartite-motif family-like2 (TRIML2) at the telomeric end of the long arm of human chromosome 4 exist in all four representative species (Fig 1-1)

Summary

Introduction

Gene duplication is one of the most common approaches for new gene to emerge. Despite the impotence of gene duplication in evolution, adding additional copies can pose major challenges to the organism due to the changes in gene dosage. Orthologs, i.e. genes found in different species that can be traced back to a single genomic locus in a common ancestor, are more likely to show similarities in their expression patterns and/or functions (Kaessmann 2010). Homology based phylogenetic reconstruction followed by reconciliation with species tree is one of the most important ways to infer the sequence and time of the major evolutionary events, i.e. speciation and duplication events, that gave rise to the gene family (Capra et al 2013). In ML method, the likelihoods of different tree topologies are calculated based on the substitution model, and the tree topology with the maximum likelihood is inferred as most plausible (Felsenstein 1981). The posterior probability is used as the measure of the confidence of the estimate (Rannala and Yang, 1996)

Methods

Results

Conclusion