Repeated losses of PRDM9-directed recombination despite the conservation of PRDM9 across vertebrates
- Columbia University, United States
- Centro de Investigaciones Científicas de las Huastecas "Aguazarca", Mexico
Abstract
Studies of highly diverged species have revealed two mechanisms by which meiotic recombination is directed to the genome—through PRDM9 binding or by targeting promoter-like features—that lead to dramatically different evolutionary dynamics of hotspots. Here, we identify PRDM9 orthologs from genome and transcriptome data in 225 species. We find the complete PRDM9 ortholog across distantly related vertebrates but, despite this broad conservation, infer a minimum of six partial and three complete losses. Strikingly, taxa carrying the complete ortholog of PRDM9 are precisely those with rapid evolution of its predicted binding affinity, suggesting that all domains are necessary for directing recombination. Indeed, as we show, swordtail fish carrying only a partial but conserved ortholog share recombination properties with PRDM9 knock-outs.
Data availability
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Xiphophorus birchmanni and Xiphophorus malinche RNAseq data Raw sequence readsPublicly available at the NCBI BioProject (accession no: PRJNA358086).
Article and author information
Author details
Funding
National Institutes of Health (R01 GM83098)
- Molly Przeworski
National Science Foundation (DDIG DEB-1405232)
- Molly Schumer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animals used for this study were handled according to the approved institutional animal care and use committee (IACUC) protocol AUP# - IACUC 2013-0168 of Texas A&M University. All individuals used for dissections were first treated with MS-222 for anesthesia to minimize suffering before being euthanized.
Copyright
© 2017, Baker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Repeated losses of PRDM9-directed recombination despite the conservation of PRDM9 across vertebrates
eLife 6:e24133.
https://doi.org/10.7554/eLife.24133
Further reading
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- Genetics and Genomics
The ways in which recombination sites are determined during meiosis are becoming clearer following a phylogenomic analysis for 225 different species.
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- Chromosomes and Gene Expression
- Genetics and Genomics
Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here, we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Although gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.
