Molecular mechanisms for environmentally induced and evolutionarily rapid redistribution (plasticity) of meiotic recombination

Abstract

It has long been known (circa 1917) that environmental conditions, as well as speciation, can affect dramatically the frequency distribution of Spo11/Rec12-dependent meiotic recombination. Here, by analyzing DNA sequence-dependent meiotic recombination hotspots in the fission yeast Schizosaccharomyces pombe, we reveal a molecular basis for these phenomena. The impacts of changing environmental conditions (temperature, nutrients, osmolarity) on local rates of recombination are mediated directly by DNA site-dependent hotspots (M26, CCAAT, Oligo-C). This control is exerted through environmental condition-responsive signal transduction networks (involving Atf1, Pcr1, Php2, Php3, Php5, Rst2). Strikingly, individual hotspots modulate rates of recombination over a very broad dynamic range in response to changing conditions. They can range from being quiescent to being highly proficient at promoting activity of the basal recombination machinery (Spo11/Rec12 complex). Moreover, each different class of hotspot functions as an independently controlled rheostat; a condition that increases the activity of one class can decrease the activity of another class. Together, the independent modulation of recombination rates by each different class of DNA site-dependent hotspots (of which there are many) provides a molecular mechanism for highly dynamic, large-scale changes in the global frequency distribution of meiotic recombination. Because hotspot-activating DNA sites discovered in fission yeast are conserved functionally in other species, this process can also explain the previously enigmatic, Prdm9-independent, evolutionarily rapid changes in hotspot usage between closely related species, subspecies, and isolated populations of the same species.

Adaptive Control of the Meiotic Recombination Landscape by DNA Site-dependent Hotspots With Implications for Evolution

“…The new discoveries support a model for environmentally induced plasticity of the meiotic recombination landscape (Figure 2D) (Protacio et al, 2022). Each class of hotspotactivating DNA sites functions as an independently controlled rheostat that modulates rates of recombination at its own locations in the genome in response to its own constellation of signals.…”

“…Such factors can complicate the interpretation of hotspot maps. More fundamentally, the process of annotating the positions of hotspots can be misleading because—as described subsequently in this perspective—individual hotspots actually function as rheostats that can variably modulate rates of recombination over a broad dynamic range ( Brown et al, 2020 ; Protacio et al, 2022 ). From our perspective, these factors are germane to long-recognized, mechanistically enigmatic features of the meiotic recombination landscape.…”

“…However, while changes in the SC could affect recombination rates at broad scale (e.g., at the level of whole chromosomes), it is difficult to envision how the SC could mediate dramatic changes in the fine-scale recombination landscape (e.g., Figures 1C,D ). Moreover, organisms that lack an SC, such as fission yeast ( Kohli and Bahler, 1994 ), still have fine-scale plasticity ( Hyppa et al, 2014 ; Brown et al, 2020 ; Protacio et al, 2022 ). Such localized changes in recombination rates—which are increased at some sites and decreased at others—would require perforce a means to dynamically and differentially control rates of recombination locally; i.e., at the resolution of individual recombination hotspots.…”

“…If most meiotic recombination is positioned in the genome by hotspot-activating DNA sites, then those DNA sites might directly control plasticity of the recombination landscape. A recent study took advantage of the powerful fission yeast model system to test this hypothesis ( Protacio et al, 2022 ). That study determined the effects of changes in three different environmental conditions (temperature, carbon source and osmolarity) on rates of recombination at a test locus that contained one of three hotspot-activating DNA sites ( M26 , CCAAT or Oligo-C ) or a basal recombination control that lacked those DNA sites.…”

“…It is standard practice in the field to define the positions of hotspots by applying frequency cutoff thresholds to recombination maps. However, individual DNA site-specific hotspots actually control recombination rates over a broad dynamic range in response to changing conditions ( Protacio et al, 2022 ). Consequently, the process of annotation can give the false impression that the positions of hotspots “move” from sample to sample, even when the positions of the hotspot regulating DNA sites have not changed (illustrated in Figure 2E ).…”