Zinc finger binding motifs do not explain recombination rate variation within or between species of Drosophila.

Caiti S S Heil,Mohamed A F Noor

doi:10.1371/journal.pone.0045055

Abstract

In humans and mice, the Cys2His2 zinc finger protein PRDM9 binds to a DNA sequence motif enriched in hotspots of recombination, possibly modifying nucleosomes, and recruiting recombination machinery to initiate Double Strand Breaks (DSBs). However, since its discovery, some researchers have suggested that the recombinational effect of PRDM9 is lineage or species specific. To test for a conserved role of PRDM9-like proteins across taxa, we use the Drosophila pseudoobscura species group in an attempt to identify recombination associated zinc finger proteins and motifs. We leveraged the conserved amino acid motifs in Cys2His2 zinc fingers to predict nucleotide binding motifs for all Cys2His2 zinc finger proteins in Drosophila pseudoobscura and identified associations with empirical measures of recombination rate. Additionally, we utilized recombination maps from D. pseudoobscura and D. miranda to explore whether changes in the binding motifs between species can account for changes in the recombination landscape, analogous to the effect observed in PRDM9 among human populations. We identified a handful of potential recombination-associated sequence motifs, but the associations are generally tenuous and their biological relevance remains uncertain. Furthermore, we found no evidence that changes in zinc finger DNA binding explains variation in recombination rate between species. We therefore conclude that there is no protein with a DNA sequence specific human-PRDM9-like function in Drosophila. We suggest these findings could be explained by the existence of a different recombination initiation system in Drosophila.

Highlights

Meiotic recombination is an essential process both mechanistically and evolutionarily, and should experience strong selective pressures
Prdm9 Homology Oliver et al (2009) suggested that, Prdm9 is essential for fertility in mice, it appears to be absent in Drosophila melanogaster and its function in meiosis may be lineage or even species-specific
Our attempts to identify a PRDM9-like protein involved in meiotic recombination initiation in Drosophila yielded negative results

Summary

Introduction

Meiotic recombination is an essential process both mechanistically and evolutionarily, and should experience strong selective pressures. The 13-base degenerate motif CCNCCNTNNCCNC is enriched in approximately 40% of European human hotspots, recruiting recombination machinery to initiate double strand breaks [3,4] This motif binds the Cys2His zinc finger protein PRDM9 in humans, and allelic variation at Prdm modifies hotspot activity within both humans and mice [3,5,6,7,8]. H3K4me in yeast and mouse seems to be a prominent and pre-existing mark of active recombination sites, creating a link between sequence and epigenetic features affecting recombination [9,10] This link inspired a proposed model in humans involving the recognition of a DNA sequence motif by PRDM9 and the modification of adjacent nucleosomes by the SET domain [11]. The conserved topoisomerase II-like protein SPO11 subsequently recognizes one or several of these signals, binds to the DNA at that location, and initiates recombination by a double strand break (DSB)

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Results

Conclusion