Evolutionary Analyses and Natural Selection of Betaine-Homocysteine S-Methyltransferase (BHMT) and BHMT2 Genes

Betaine-homocysteine S-methyltransferase (BHMT) and BHMT2 convert homocysteine to methionine using betaine and S-methylmethionine, respectively, as methyl donor substrates. Increased levels of homocysteine in blood are associated with cardiovascular disease. Given their role in human health and nutrition, we identified BHMT and BHMT2 genes and proteins from 38 species of deuterostomes including human and non-human primates. We aligned the genes to look for signatures of selection, to infer evolutionary rates and events across lineages, and to identify the evolutionary timing of a gene duplication event that gave rise to two genes, BHMT and BHMT2. We found that BHMT was present in the genomes of the sea urchin, amphibians, reptiles, birds and mammals; BHMT2 was present only across mammals. BHMT and BHMT2 were present in tandem in the genomes of all monotreme, marsupial and placental species examined. Evolutionary rates were accelerated for BHMT2 relative to BHMT. Selective pressure varied across lineages, with the highest dN/dS ratios for BHMT and BHMT2 occurring immediately following the gene duplication event, as determined using GA Branch analysis. Nine codons were found to display signatures suggestive of positive selection; these contribute to the enzymatic or oligomerization domains, suggesting involvement in enzyme function. Gene duplication likely occurred after the divergence of mammals from other vertebrates but prior to the divergence of extant mammalian subclasses, followed by two deletions in BHMT2 that affect oligomerization and methyl donor specificity. The faster evolutionary rate of BHMT2 overall suggests that selective constraints were reduced relative to BHMT. The dN/dS ratios in both BHMT and BHMT2 was highest following the gene duplication, suggesting that purifying selection played a lesser role as the two paralogs diverged in function

Mother’s Pre-pregnancy BMI and Placental Candidate miRNAs: Findings from the ENVIRONAGE Birth Cohort

There is increasing evidence that the predisposition for development of chronic diseases arises at the earliest times of life. In this context, maternal pre-pregnancy weight might modify fetal metabolism and the child's predisposition to develop disease later in life. The aim of this study is to investigate the association between maternal pre-pregnancy body mass index (BMI) and miRNA alterations in placental tissue at birth. In 211 mother-newborn pairs from the ENVIRONAGE birth cohort, we assessed placental expression of seven miRNAs important in crucial cellular processes implicated in adipogenesis and/or obesity. Multiple linear regression models were used to address the associations between pre-pregnancy BMI and placental candidate miRNA expression. Maternal pre-pregnancy BMI averaged (+/- SD) 23.9 (+/- 4.1) kg/m(2). In newborn girls ( not in boys) placental miR-20a, miR-34a and miR-222 expression was lower with higher maternal pre-pregnancy BMI. In addition, the association between maternal pre-pregnancy BMI and placental expression of these miRNAs in girls was modified by gestational weight gain. The lower expression of these miRNAs in placenta in association with pre-pregnancy BMI, was only evident in mothers with low weight gain (< 14 kg). The placental expression of miR-20a, miR-34a, miR-146a, miR-210 and miR-222 may provide a sex-specific basis for epigenetic effects of pre-pregnancy BMI.The ENVIRONAGE birth cohort is supported by grants from the European Research Council (ERC-2012-StG310898) and Flemish Research Council (FWO G073315N). Karen Vrijens is a postdoctoral fellow of the FWO (12D7714N)

Primate vaginal microbiomes exhibit species specificity without universal Lactobacillus dominance

Bacterial communities colonizing the reproductive tracts of primates (including humans) impact the health, survival and fitness of the host, and thereby the evolution of the host species. Despite their importance, we currently have a poor understanding of primate microbiomes. The composition and structure of microbial communities vary considerably depending on the host and environmental factors. We conducted comparative analyses of the primate vaginal microbiome using pyrosequencing of the 16S rRNA genes of a phylogenetically broad range of primates to test for factors affecting the diversity of primate vaginal ecosystems. The nine primate species included: humans (Homo sapiens), yellow baboons (Papio cynocephalus), olive baboons (Papio anubis), lemurs (Propithecus diadema), howler monkeys (Alouatta pigra), red colobus (Piliocolobus rufomitratus), vervets (Chlorocebus aethiops), mangabeys (Cercocebus atys) and chimpanzees (Pan troglodytes). Our results indicated that all primates exhibited host-specific vaginal microbiota and that humans were distinct from other primates in both microbiome composition and diversity. In contrast to the gut microbiome, the vaginal microbiome showed limited congruence with host phylogeny, and neither captivity nor diet elicited substantial effects on the vaginal microbiomes of primates. Permutational multivariate analysis of variance and Wilcoxon tests revealed correlations among vaginal microbiota and host species-specific socioecological factors, particularly related to sexuality, including: female promiscuity, baculum length, gestation time, mating group size and neonatal birth weight. The proportion of unclassified taxa observed in nonhuman primate samples increased with phylogenetic distance from humans, indicative of the existence of previously unrecognized microbial taxa. These findings contribute to our understanding of host–microbe variation and coevolution, microbial biogeography, and disease risk, and have important implications for the use of animal models in studies of human sexual and reproductive diseases