Biology subjects

Vernot, B.

Publications and source records attributed to Vernot, B..

4 recordsLinked to original sources

bioRxiv2021

Characterization of RNA content in individual phase-separated coacervate microdroplets

Liquid-liquid phase separation or condensation is a form of macromolecular compartmentalization. Condensates formed by complex coacervation were hypothesized to have played a crucial part during the origin-of-life. In living cells, condensation organizes biomolecules into a wide range of membraneless compartments. Although RNA is a key component of condensation in cells and the central component of the RNA world hypothesis, little is known about what determines RNA accumulation in condensates and how single condensates differ in their RNA composition. Therefore, we developed an approach to read the RNA content from single condensates using high-throughput sequencing. We find that RNAs which are enriched for specific sequence motifs efficiently accumulate in condensates. These motifs show high sequence similarity to short interspersed elements (SINEs). We observed similar results for protein-derived condensates, demonstrating applicability across different in vitro reconstituted membraneless organelles. Thus, our results provide a new inroad to explore the RNA content of phase-separated droplets at single condensate resolution.

genomics↗

bioRxiv2020

The evolutionary history of Neandertal and Denisovan Y chromosomes

Ancient DNA has allowed the study of various aspects of human history in unprecedented detail. However, because the majority of archaic human specimens preserved well enough for genome sequencing have been female, comprehensive studies of Y chromosomes of Denisovans and Neandertals have not yet been possible. Here we present sequences of the first Denisovan Y chromosomes (Denisova 4 and Denisova 8), as well as the Y chromosomes of three late Neandertals (Spy 94a, Mezmaiskaya 2 and El Sidron 1253). We find that the Denisovan Y chromosomes split around 700 thousand years ago (kya) from a lineage shared by Neandertal and modern human Y chromosomes, which diverged from each other around 370 kya. The phylogenetic relationships of archaic and modern human Y chromosomes therefore differ from population relationships inferred from their autosomal genomes, and mirror the relationships observed on the level of mitochondrial DNA. This provides strong evidence that gene flow from an early lineage related to modern humans resulted in the replacement of both the mitochondrial and Y chromosomal gene pools in late Neandertals. Although unlikely under neutrality, we show that this replacement is plausible if the low effective population size of Neandertals resulted in an increased genetic load in their Y chromosomes and mitochondrial DNA relative to modern humans.

evolutionary biology↗

bioRxiv2018

The limits of long-term selection against Neandertal introgression

Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans due to deleterious alleles that had accumulated in the Neandertals after they split from the modern human lineage. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45 thousand years. Here we show that this apparent decline is an artifact caused by gene flow between West Eurasians and Africans, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When applying a more robust statistic that takes advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Western Europe over the past 45 thousand years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters, and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular a depletion of Neandertal ancestry in conserved genomic regions that are likely to be of functional importance. Thus, we find that negative selection against Neandertal ancestry has not played as strong a role in recent human evolution as had previously been assumed.

evolutionary biology↗

bioRxiv2018

Human stem cell resources are an inroad to Neandertal DNA functions

Pluripotent stem cells from diverse humans offer the potential to study human functional variation in controlled culture environments. A portion of this variation originates from ancient admixture between modern humans and Neandertals, which introduced alleles that left a phenotypic legacy on individual humans today. Here we show that a large repository of human induced pluripotent stem cells (iPSCs) harbors extensive Neandertal DNA, including most known functionally relevant Neandertal alleles present in modern humans. This resource contains Neandertal DNA that contributes to human phenotypes and diseases, encodes hundreds of amino acid changes, and alters gene expression in specific tissues. Human iPSCs thus provide an opportunity to experimentally explore the Neandertal contribution to present-day phenotypes, and potentially study Neandertal traits.

evolutionary biology↗