Nordgren, C. E. | bioRxiv Science

bioRxiv2024

A spatiotemporally resolved atlas of mRNA decay in the C. elegans embryo reveals differential regulation of mRNA stability across stages and cell types

During embryonic development, cells undergo dynamic changes in gene expression that are required for appropriate cell fate specification. Although both transcription and mRNA degradation contribute to gene expression dynamics, patterns of mRNA decay are less well-understood. Here we directly measured spatiotemporally resolved mRNA decay rates transcriptome-wide throughout C. elegans embryogenesis by transcription inhibition followed by bulk and single-cell RNA-sequencing. This allowed us to calculate mRNA half-lives within specific cell types and developmental stages and identify differentially regulated mRNA decay throughout embryonic development. We identified transcript features that are correlated with mRNA stability and found that mRNA decay rates are associated with distinct peaks in gene expression over time. Moreover, we provide evidence that, on average, mRNA is more stable in the germline compared to in the soma and in later embryonic stages compared to in earlier stages. This work suggests that differential mRNA decay across cell states and time helps to shape developmental gene expression, and it provides a valuable resource for studies of mRNA turnover regulatory mechanisms.

developmental biology↗

bioRxiv2023

The genomic landscape, causes, and consequences of extensive phylogenomic discordance in Old World mice and rats

A species tree is a central concept in evolutionary biology whereby a single branching phylogeny reflects relationships among species. However, the phylogenies of different genomic regions often differ from the species tree. Although tree discordance is often widespread in phylogenomic studies, we still lack a clear understanding of how variation in phylogenetic patterns is shaped by genome biology or the extent to which discordance may compromise comparative studies. We characterized patterns of phylogenomic discordance across the murine rodents (Old World mice and rats) - a large and ecologically diverse group that gave rise to the mouse and rat model systems. Combining new linked-read genome assemblies for seven murine species with eleven published rodent genomes, we first used ultra-conserved elements (UCEs) to infer a robust species tree. We then used whole genomes to examine finer-scale patterns of discordance and found that phylogenies built from proximate chromosomal regions had similar phylogenies. However, there was no relationship between tree similarity and local recombination rates in house mice, suggesting that genetic linkage influences phylogenetic patterns over deeper timescales. This signal may be independent of contemporary recombination landscapes. We also detected a strong influence of linked selection whereby purifying selection at UCEs led to less discordance, while genes experiencing positive selection showed more discordant and variable phylogenetic signals. Finally, we show that assuming a single species tree can result in high error rates when testing for positive selection under different models. Collectively, our results highlight the complex relationship between phylogenetic inference and genome biology and underscore how failure to account for this complexity can mislead comparative genomic studies.

evolutionary biology↗