Biology subjects

Mika, K.

Publications and source records attributed to Mika, K..

8 recordsLinked to original sources

bioRxiv2021

Transposable elements continuously remodel the regulatory landscape, transcriptome, and function of decidual stromal cells

Gene expression evolution underlies the origin, divergence, and conservation of biological characters including cell-types, tissues, and organ systems. Previously we showed that large-scale gene expression changes in decidual stromal cells contributed to the origins of pregnancy in eutherians and the divergence of pregnancy traits in primates, and that transposable elements likely contributed to these gene expression changes. Here we show that two large waves of TEs remodeled the transcriptome and regulatory landscape of decidual stromal cells, including a major wave in primates. Genes nearby TE-derived regulatory elements are among the most progesterone responsive in the genome and play essential roles in orchestrating progesterone responsiveness and the core function of decidual cells by donating progesterone receptor binding sites to the genome. We tested the regulatory abilities of 89 TE consensus sequences and found nearly all acted as repressors in mammalian cells, but treatment with a histone deacetylase inhibitor unmasked latent enhancer functions. These data indicate TEs have played an important role in the development, evolution, and function of primate decidual stromal cells and suggest a two-step model in which latent enhancer functions of TEs are unmasked after they lose primary repressors functions. Significance statementGene expression patterns evolved very rapidly during the evolutionary origins of pregnancy in early mammals and in primates. These episodes of gene expression evolution and linked with important processes that establish and maintain pregnancy, and appear to be driven by domestication of transposable elements.

evolutionary biology↗

bioRxiv2021

Gene expression phylogenies and ancestral transcriptome reconstruction resolves major transitions in the origins of pregnancy

Structural and physiological changes in the female reproductive system underlie the origins of pregnancy in multiple vertebrate lineages. In mammals, for example, the glandular portion of the lower reproductive tract has transformed into a structure specialized for supporting fetal development. These specializations range from relatively simple maternal provisioning in egg-laying monotremes to an elaborate suite of traits that support intimate maternal-fetal interactions in Eutherians. Among these traits are the maternal decidua and fetal component of the placenta, but there is considerable uncertainty about how these structures evolved. We identified the origins of pregnancy utilizing ancestral transcriptome reconstruction to infer functional evolution of the maternal-fetal interface. Remarkably, we found that maternal gene expression profiles are correlated with degree of placental invasion. These results indicate that an epitheliochorial-like placenta evolved early in the mammalian stem-lineage and that the ancestor of Eutherians had a hemochorial placenta, and suggest maternal control of placental invasiveness. Collectively, these data resolve major transitions in the evolution of pregnancy and indicate that ancestral transcriptome reconstruction can be used to study the function of ancestral cell, tissue, and organ systems.

evolutionary biology↗

bioRxiv2021

Olfactory receptor-dependent receptor repression in Drosophila

In olfactory systems across phyla, most sensory neurons transcribe a single olfactory receptor gene selected from a large genomic repertoire. We describe novel receptor gene-dependent mechanisms that ensure singular expression of receptors encoded by a tandem gene array in Drosophila. Transcription from upstream genes in the cluster runs through the coding region of downstream loci to inhibit their expression in cis, via transcriptional interference. Moreover, one receptor blocks expression of other receptor proteins in trans through a post-transcriptional mechanism. These repression mechanisms operate in endogenous neurons to ensure their unique expression. Our data provide evidence for inter-olfactory receptor regulation in invertebrates, and highlight unprecedented, but potentially widespread, mechanisms for ensuring exclusive expression of chemosensory receptors, and other protein families, encoded by tandemly-arranged genes.

neuroscience↗

bioRxiv2021

Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes

Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian ("Placental") mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy. We found that hundreds of genes gained or lost endometrial expression in the human lineage. Among these are genes that may contribute to human-specific maternal-fetal communication (HTR2B) and maternal-fetal immunotolerance (PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion (CORIN). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. We also anticipate our results will advance the emerging synthesis of evolution and medicine ("evolutionary medicine") and be a starting point for more sophisticated studies of the maternal-fetal interface. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.

evolutionary biology↗

bioRxiv2020

Intergenerational microbial transmission in the little skate (Leucoraja erinacea)

BackgroundMicrobial transmission from parent to offspring is hypothesized to be widespread in vertebrates. However, evidence for this is limited as many evolutionarily important clades remain unexamined. There is currently no data on the microbiota associated with any Chondrichthyan species during embryonic development, despite the global distribution, ecological importance, and phylogenetic position of this clade. In this study, we take the first steps towards filling this gap by investigating the microbiota associated with embryonic development in the little skate, Leucoraja erinacea, a common North Atlantic species and popular system for chondrichthyan biology. MethodsTo assess the potential for bacterial transmission in an oviparous chondrichthyan, we used 16S rRNA amplicon sequencing to characterize the microbial communities associated with the skin, gill, and egg capsule of the little skate, at six points during ontogeny. Community composition was analyzed using the QIIME2 pipeline and microbial continuity between stages was tracked using FEAST. ResultsWe identify site-specific and stage-specific microbiota dominated by the bacterial phyla Proteobacteria and Bacteroidetes. This composition is similar to, but distinct from, that of previously published data on the adult microbiota of other chondrichthyan species. Our data reveal that the skate egg capsule harbors a highly diverse bacterial community-particularly on the internal surface of the capsule-and facilitates intergenerational microbial transfer to the offspring. Embryonic skin and external gill tissues host similar bacterial communities; the skin and gill communities later diverge as the internal gills and skin denticles develop. ConclusionsOur study is the first exploration of the chondrichthyan microbiota throughout ontogeny and provides the first evidence of vertical transmission in this group.

microbiology↗

bioRxiv2020

Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length

The developmental origins and evolutionary histories of cell types, tissues and organ systems contribute to the ways in which their dysfunction leads to disease. In mammals for example, the nature and extent of maternal-fetal interactions, how those interactions develop, and their evolutionary history likely influence diseases of pregnancy such as infertility and preterm birth. Here we show genes that evolved to be expressed at the maternal-fetal interface in Eutherian ( Placental) mammals play essential roles in the evolution of pregnancy and are associated with immune system disorders and preterm birth. Among these genes is the transcription factor HAND2, which suppresses estrogen signaling, an innovation of Eutherians, thereby allowing blastocyst implantation. We found that HAND2 is dynamically expressed in the decidua throughout the menstrual cycle and pregnancy, gradually decreasing to reach a low at term. HAND2 regulates a small but distinct set of target genes in endometrial stromal fibroblasts including the cytokine IL15, which was also dynamically expressed throughout the menstrual cycle and gestation, and promoted the migration of natural killer cells and extravillous cytotrophoblasts. Remarkably, we found that the HAND2 promoter loops to a distal enhancer containing SNPs implicated in the regulation of gestation length and birth weight. Collectively, these data connect HAND2 expression at the maternal-fetal interface with the evolution of implantation and gestation length regulation, and preterm birth.

evolutionary biology↗

bioRxiv2020

KD-64 - a new selective A2A adenosine receptor antagonist has anti-inflammatory activity but contrary to the non-selective antagonist - caffeine does not reduce diet-induced obesity in mice

The A2 adenosine receptors play an important role, among others, in the regulation of inflammatory process and glucose homeostasis in diabetes and obesity. Thus, the presented project evaluated of influence of the selective antagonist of A2A adenosine receptor - KD-64 as compared to the known non-selective antagonist - caffeine on these two particular processes. Two different inflammation models were induced namely local and systemic inflammation. Obesity was induced in mice by high-fat diet and the tested compounds (KD-64 and caffeine) were administrated for 21 days. KD-64 showed anti-inflammatory effect in both tested inflammation models and administered at the same dose as ketoprofen exerted stronger effect than this reference compound. Elevated levels of IL-6 and TNF- observed in obese control mice were significantly lowered by the administration of KD-64 and were similar to the values observed in control non-obese mice. Interestingly, caffeine increased the levels of these parameters. In contrast to caffeine which had no influence on AlaT activity, KD-64 administration significantly lowered AlaT activity in the obese mice. Although, contrary to caffeine, KD-64 did not reduce diet-induced obesity in mice, it improved glucose tolerance. Thus, the activity of the selective adenosine A2A receptor antagonist was quite different from that of the non-selective.

pharmacology and toxicology↗

bioRxiv2016

Transposable element exaptation is the primary source of novelty in the primate gene regulatory landscape

Gene regulation plays a critical role in the evolution of phenotypic diversity. We investigated the evolution of liver promoters and enhancers in six primate species. We performed ChlP-seq for two histone modifications and RNA-seq to profile cis-regulatory element (CRE) activity and gene expression. The primate regulatory landscape is largely conserved across the lineage. Conserved CRE function is associated with sequence conservation, proximity to coding genes, cell type specificity of CRE function, and transcription factor binding. Newly evolved CREs are enriched in immune response and neurodevelopmental functions, while conserved CREs bind master regulators. Transposable elements (TEs) are the primary source of novelty in primate gene regulation. Newly evolved CREs are enriched in young TEs that affect gene expression. However, only 17% of conserved CREs overlap a TE, suggesting that target gene expression is under strong selection. Finally, we identified specific genomic features driving the functional recruitment of newly inserted TEs.

genomics↗