Abstract
Meiosis is initiated by a double-strand break (DSB) introduced in the DNA by a highly controlled process that is repaired by recombination. In many organisms, recombination occurs at specific and narrow regions of the genome, known as recombination hotspots, which overlap with regions enriched for DSBs. In recent years, it has been demonstrated that conversions and mutations resulting from the repair of DSBs lead to a rapid sequence evolution at recombination hotspots eroding target sites for DSBs. We still do not fully understand the effect of this erosion in the recombination activity, but evidence has shown that the binding of trans-acting factors like PRDM9 is affected. PRDM9 is a meiosis-specific, multi-domain protein that recognizes DNA target motifs by its zinc finger domain and directs DSBs to these target sites. Here we discuss the changes in affinity of PRDM9 to eroded recognition sequences, and explain how these changes in affinity of PRDM9 can affect recombination, leading sometimes to sterility in the context of hybrid crosses. We also present experimental data showing that DNA methylation reduces PRDM9 binding in vitro. Finally, we discuss PRDM9-independent hotspots, posing the question how these hotspots evolve and change with sequence erosion.This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
Highlights
The consequences of sequence erosion in the evolution of recombination hotspots Irene Tiemann-Boege, Theresa Schwarz, Yasmin Striedner and Angelika Heissl
Meiosis is initiated by a double-strand break (DSB) introduced in the DNA by a highly controlled process that is repaired by recombination
We present experimental data showing that DNA methylation reduces PRDM9 binding in vitro
Summary
Meiosis is a tightly regulated process ensuring the exchange of genetic material between homologous chromosomes, known as meiotic recombination. During the repair of the DSB, the intermediate repair structure that results in a crossover (CO) physically links the homologues (visible in cells as chiasmata), and ensures their proper segregation (reviewed in [1,2]) This exchange of genetic information is important to eliminate deleterious mutations from the genome, as was observed in asexual reproducing organisms or non-recombining regions of sexually reproducing organisms in which deleterious mutations accumulated at a higher rate [3]. During the first stages of meiotic prophase I, the chromatin undergoes substantial changes and is condensed into a tight structure formed by a series of tandem loops anchored by various proteins to axial elements at cohesion sites [29,30,31] This structural chromosomal conformation is a key determinant for the placement of DSBs in leptotene. After strand invasion of the free 30-filaments and D-loop formation, the DSB can be repaired as a CO by the resolution of a double Holliday junction (dHJ) or as a noncrossover (NCO) by single-strand invasion that generates a non-reciprocal exchange of the sequence from one homologue to the other (reviewed in [9])
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Schedule a callMore From: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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