A Hierarchical Combination of Factors Shapes the Genome-wide Topography of Yeast Meiotic Recombination Initiation

Abstract

Summary The nonrandom distribution of meiotic recombination shapes patterns of inheritance and genome evolution, but chromosomal features governing this distribution are poorly understood. Formation of the DNA double-strand breaks (DSBs) that initiate recombination results in accumulation of Spo11 protein covalently bound to small DNA fragments. We show here that sequencing these fragments provides a genome-wide DSB map of unprecedented resolution and sensitivity. We use this map to explore the influence of large-scale chromosome structures, chromatin, transcription factors, and local sequence composition on DSB distributions. Our analysis supports the view that the recombination terrain is molded by combinatorial and hierarchical interaction of factors that work on widely different size scales. Mechanistic aspects of DSB formation and early processing steps are also uncovered. This map illuminates the occurrence of DSBs in repetitive DNA elements, repair of which can lead to chromosomal rearrangements. We discuss implications for evolutionary dynamics of recombination hotspots.

High-Resolution Mapping of Crossover Events in the Hexaploid Wheat Genome Suggests a Universal Recombination Mechanism

“…Significant associations were found between hotspots and poly-A stretches (Choi et al 2013;Wijnker et al 2013;Shilo et al 2015) which are known to preferentially locate upstream of TSSs, resulting in reduced nucleosome occupancy that facilitates accessibility of the recombination machinery (Wu and Lichten 1994;Berchowitz et al 2009;Segal and Widom 2009;Pan et al 2011). Similarly, CCN-and CTT-repeat sequence motifs were also detected to be associated to recombination hotspots (Choi et al 2013;Shilo et al 2015;Wijnker et al 2013).…”

“…These authors evaluated intervals ranging from 380 to 11,600 bp where recombination varied from 22 to 132 cM/Mb compared to average chromosome values of 2.1 and 0.20 cM/Mb for maize and wheat, respectively. Like for Arabidopsis and Mimulus, CO events were more frequent in the 59 regions of genes confirming that in plants, hotspots are rather localized in promoters as this is the case in yeast (Pan et al 2011), humans, or mice (reviewed in de Massy 2013 andde Massy 2013).…”

“…According to our results, recombination in wheat seems to occur more frequently close to or within the genes as in Arabidopsis and S. cerevisiae (Pan et al 2011;Tischfield and Keeney 2012;Choi et al 2013). Recombinogenic regions also carry genes which are more prone to being expressed during meiosis, while on the contrary, cold regions carry fewer and less expressed genes.…”

“…Open chromatin structure is known to play an important role in CO formation in both yeast (Wu and Lichten 1994;Berchowitz et al 2009;Borde et al 2009;Pan et al 2011) and mammals (Buard et al 2009;Berg et al 2010;Grey et al 2011), especially through the trimethylation of lysine 4 of histone H3 (H3K4me3 landmark). DNA methylation also represses CO formation (Maloisel and Rossignol 1998) and is sufficient to silence CO hotspots in Arabidopsis (Yelina et al 2015).…”

Evolutionary mysteries in meiosis

“…There are at least two types of hotspots ( figure 3). The first type, probably ancestral, is found in fungi, plants, birds and some mammals; these hotspots are temporally stable (up to millions of years) and concentrated near promoter regions and transcription start sites [178,[182][183][184][185]. The second type is likely derived and is found in other mammals, including mice and humans, where the positioning of hotspots is determined by the zinc-finger protein PRDM9.…”