GfGyrCast
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB82249 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR13947507_1.fastq.gz | Fastqsanger.gz | |||
| ERR13947507_2.fastq.gz | Fastqsanger.gz | |||
| ERR13946486.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
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Project description:PRDM9, a histone methyltransferase, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we compared activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced. Comparing these two strains, we find that haplotype differences at hotspots leads to qualitative and quantitative changes in PRDM9 binding and activity. Most variants affecting PRDM9Cst binding arose and were fixed in M.m castaneus, suppressing hotspot activity. Furthermore, M.m castaneus x M.m domesticus F1 hybrids exhibit novel hotspots, representing sites of historic evolutionary erosion. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion. Identify position of meiotic H3K4me3 from various sub-species of mice and F1 hybrids from crosses between subspecies. In addition, perform ChIP-seq analysis on the meiosis-specific methyltransferase PRDM9.
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Project description:A key goal of evolutionary genomics is to harness molecular data from wild isolates to draw inferences about selective forces that have acted on genomes. The field progresses in large part through the development and benchmarking of advanced molecular-evolution analysis methods. Here we evaluated the rigor and performance of a test of directional, cis-regulatory evolution across genes in pathways, using stem cells across Mus musculus subspecies as a model. We discovered a unique program of induction of translation-related genes in stem cells of the Southeast Asian mouse M. m. castaneus relative to its sister taxa, driven in part by cis-regulatory variation. As a complement, we used sequence analyses to find population- and comparative-genomic signatures of selection in M. m. castaneus, at the upstream regions of the ribosomal gene cohort. The unique high-expression program for these loci in M. m. castaneus was recapitulated in stem cell-derived neurons. We interpret our data under a model of changes in lineage-specific pressures across Mus musculus for high translational capacity in stem cells and their descendant cells. Together, our findings underscore the rigor of integrating expression and sequence-based methods to generate hypotheses about evolutionary events from long ago.
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Project description:PRDM9, a histone methyltransferase, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we compared activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced. Comparing these two strains, we find that haplotype differences at hotspots leads to qualitative and quantitative changes in PRDM9 binding and activity. Most variants affecting PRDM9Cst binding arose and were fixed in M.m castaneus, suppressing hotspot activity. Furthermore, M.m castaneus x M.m domesticus F1 hybrids exhibit novel hotspots, representing sites of historic evolutionary erosion. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion.
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