Correction: Stem cell transcriptional profiles from mouse subspecies reveal cis-regulatory evolution at translation genes
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Stem cell transcriptional profiles from mouse subspecies reveal cis-regulatory evolution at translation genes
A key goal of evolutionary genomics is to harness molecular data to draw inferences about selective forces that have acted on genomes. The field progresses in large part through the development of advanced molecular-evolution analysis methods. Here we explored the intersection between classical sequence-based tests for selection and an empirical expression-based approach, using stem cells from Mus musculus subspecies as a model. Using a test of directional, cis-regulatory evolution across genes in pathways, we discovered a unique program of induction of translation genes in stem cells of the Southeast Asian mouse M. m. castaneus relative to its sister taxa. We then mined population-genomic sequences to pursue underlying regulatory mechanisms for this expression divergence, finding robust evidence for alleles unique to M. m. castaneus at the upstream regions of the translation genes. We interpret our data under a model of changes in lineage-specific pressures across Mus musculus in stem cells with high translational capacity. Our findings underscore the rigor of integrating expression and sequence-based methods to generate hypotheses about evolutionary events from long ago.
Influence of geographic isolation and the environment on gene flow among phenotypically diverse lizards
Lizards in the genus Anolis comprise hundreds of species that display a wide range of phenotypic variation closely related to their environment. One example is the Guadeloupean anole (Anolis marmoratus ssp.) that display extreme phenotypic variation, primarily in adult male color and pattern, with twelve described subspecies on the archipelago. Here we examine the relationship between phenotypic and genetic divergence among five subspecies on the two main islands and test the role of geographic isolation and the environment in reducing gene flow. We also examined two offshore island populations to assess the impact of complete geographic isolation on gene flow. We analyzed color phenotypes by measuring spectral reflectance and genomic diversity using SNPs. Genetic divergence was correlated with dorsolateral head and body color phenotypes, and slope and geographic distance were nearly equivalent at explaining this divergence. There was minimal genome-wide divergence at neutral loci among phenotypically disparate subspecies on the two main islands and their differentiation is consistent with a model of divergence with gene flow. Our spatial visualization of gene flow showed an impact of environmental features consistent with a hypothesis of ecologically driven divergence. Nonetheless, subspecies on the two main islands remain interconnected by substantial gene flow and their phenotypic variation is likely maintained at selection-gene flow equilibrium by divergent selection at loci associated with their color phenotypes. Greater isolation, such as inhabiting a remote island, may be required for reducing gene flow. Our findings highlight the role of the environment, adaptation, and geographic isolation on gene flow.
The contribution of genetic determinants of blood gene expression and splicing to molecular phenotypes and health outcomes
The biological mechanisms through which most nonprotein-coding genetic variants affect disease risk are unknown. To investigate gene-regulatory mechanisms, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through bulk RNA sequencing in 4,732 participants and integrated protein, metabolite and lipid data from the same individuals. We identified cis-QTLs for the expression of 17,233 genes and 29,514 splicing events (in 6,853 genes). Colocalization analyses revealed 3,430 proteomic and metabolomic traits with a shared association signal with either gene expression or splicing. We quantified the relative contribution of the genetic effects at loci with shared etiology, observing 222 molecular phenotypes significantly mediated by gene expression or splicing. We uncovered gene-regulatory mechanisms at disease loci with therapeutic implications, such as WARS1 in hypertension, IL7R in dermatitis and IFNAR2 in COVID-19. Our study provides an open-access resource on the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans (https://IntervalRNA.org.uk).
The Marchantia polymorpha pangenome reveals ancient mechanisms of plant adaptation to the environment
Plant adaptation to terrestrial life started 450 million years ago and has played a major role in the evolution of life on Earth. The genetic mechanisms allowing this adaptation to a diversity of terrestrial constraints have been mostly studied by focusing on flowering plants. Here, we gathered a collection of 133 accessions of the model bryophyte Marchantia polymorpha and studied its intraspecific diversity using selection signature analyses, a genome–environment association study and a pangenome. We identified adaptive features, such as peroxidases or nucleotide-binding and leucine-rich repeats (NLRs), also observed in flowering plants, likely inherited from the first land plants. The M. polymorpha pangenome also harbors lineage-specific accessory genes absent from seed plants. We conclude that different land plant lineages still share many elements from the genetic toolkit evolved by their most recent common ancestor to adapt to the terrestrial habitat, refined by lineage-specific polymorphisms and gene family evolution.
Characterization of cis-polyisoprene produced in Periploca sepium, a novel promising alternative source of natural rubber
Natural rubber is an important industrial raw material and is almost exclusively produced from Hevea brasiliensis latex. Because H. brasiliensis is limited its cultivation to specific tropical regions, the insufficient capacity of natural rubber has become increasingly urgent. To develop a novel alternative plant for natural rubber production, we selected a perennial shrub Periploca sepium, which is widely distributed from tropical to temperate regions. P. sepium can produce latex and contains the rubber component polyisoprene with a high-molecular-weight distribution ranging from 104-106. Its main chain structure was identified as cis-1,4-polyisoprene, similar to that of H. brasiliensis. The polyisoprenes were observed to be present mainly in the secondary phloem adjacent to the cambium and pith, and almost entirely overlapped with the distributions of three rubber particle-associated proteins, cis-prenyltransferase (CPT), small rubber particle protein (SRPP) and rubber elongation factor (REF). The three genes were genome edited via CRISPR-Cas9 in P. sepium, and the total contents and high-molecular-mass regions of the cis-polyisoprenes in the transgenic plants with mutations were reduced to different degrees, indicating that the three genes apparently play important roles in natural rubber biosynthesis. This research will promote the development of P. sepium as an alternative source of natural rubber.
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