O'Neill, M. J. | bioRxiv Science

bioRxiv2018

Tissue-specific transcriptome for Poeciliopsis prolifica reveals evidence for genetic adaptation related to the evolution of a placental fish.

The evolution of the placenta is an excellent model to examine the evolutionary processes underlying adaptive complexity due to the recent, independent derivation of placentation in divergent animal lineages. In fishes, the family Poeciliidae offers the opportunity to study placental evolution with respect to variation in degree of post-fertilization maternal provisioning among closely related sister species. In this study, we present a detailed examination of a new reference transcriptome sequence for the live-bearing, matrotrophic fish, Poeciliopsis prolifica, from multiple-tissue RNA-seq data. We describe the genetic components active in liver, brain, late-stage embryo, and the maternal placental/ovarian complex, as well as associated patterns of positive selection in a suite of orthologous genes found in fishes. Results indicate the expression of many signaling transcripts, \"non-coding\" sequences and repetitive elements in the maternal placental/ovarian complex. Moreover, patterns of positive selection in protein sequence evolution were found associated with live-bearing fishes, generally, and the placental P. prolifica, specifically, that appear independent of the general live-bearer lifestyle. Much of the observed patterns of gene expression and positive selection are congruent with the evolution of placentation in fish functionally converging with mammalian placental evolution and with the patterns of rapid evolution facilitated by the teleost-specific whole genome duplication event.

genomics↗

bioRxiv2018

Loss of Trem2 in microglia leads to widespread disruption of cell co-expression networks in mouse brain

Rare heterozygous coding variants in the Triggering Receptor Expressed in Myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer's disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. Using brain cell type markers and ontology enrichment, we found subnetworks with cell type and/or functional identity. We primarily discovered changes in an endothelial-gene enriched subnetwork at 4 months, including a shift towards a more central role for the Amyloid Precursor Protein (App) gene, coupled with widespread disruption of other cell-type subnetworks, including a subnetwork with neuronal identity. We reveal an unexpected potential role of Trem2 in the homeostasis of endothelial cells that goes beyond its known functions as a microglial receptor and signalling hub, suggesting an underlying link between immune response and vascular disease in dementia.

systems biology↗