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
-
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.
Metrics
-
- 5,436
- views
-
- 714
- downloads
-
- 130
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
-
- Genetics and Genomics
The ways in which recombination sites are determined during meiosis are becoming clearer following a phylogenomic analysis for 225 different species.
-
- Genetics and Genomics
RNA-binding proteins (RBPs) perform diverse functions including the regulation of chromatin dynamics and the coupling of transcription with RNA processing. However, our understanding of their actions in mammalian neurons remains limited. Using affinity purification, yeast-two-hybrid and proximity ligation assays, we identified interactions of multiple RBPs with neural retina leucine (NRL) zipper, a Maf-family transcription factor critical for retinal rod photoreceptor development and function. In addition to splicing, many NRL-interacting RBPs are associated with R-loops, which form during transcription and increase during photoreceptor maturation. Focusing on DHX9 RNA helicase, we demonstrate that its expression is modulated by NRL and that the NRL–DHX9 interaction is positively influenced by R-loops. ssDRIP-Seq analysis reveals both stranded and unstranded R-loops at distinct genomic elements, characterized by active and inactive epigenetic signatures and enriched at neuronal genes. NRL binds to both types of R-loops, suggesting an epigenetically independent function. Our findings suggest additional functions of NRL during transcription and highlight complex interactions among transcription factors, RBPs, and R-loops in regulating photoreceptor gene expression in the mammalian retina.
