Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA.
Genetics. 2022 Feb 4;220(2). doi: 10.1093/genetics/iyab212.
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, and osmolarity) on local rates of recombination are mediated directly by DNA site-dependent hotspots (M26, CCAAT, and Oligo-C). This control is exerted through environmental condition-responsive signal transduction networks (involving Atf1, Pcr1, Php2, Php3, Php5, and 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.
长期以来,人们已经知道(大约在 1917 年),环境条件以及物种形成会极大地影响 Spo11/Rec12 依赖性减数分裂重组的频率分布。在这里,通过分析裂殖酵母 Schizosaccharomyces pombe 中依赖于 DNA 序列的减数分裂重组热点,我们揭示了这些现象的分子基础。改变环境条件(温度、营养和渗透压)对局部重组率的影响是通过 DNA 位点依赖性热点(M26、CCAAT 和寡聚-C)直接介导的。这种控制是通过环境条件响应信号转导网络(涉及 Atf1、Pcr1、Php2、Php3、Php5 和 Rst2)发挥作用的。引人注目的是,单个热点可以在很宽的动态范围内响应变化的条件来调节重组率。它们的范围可以从静止到非常有效地促进基本重组机制(Spo11/Rec12 复合物)的活性。此外,每个不同类别的热点都作为一个独立控制的变阻器发挥作用;一种条件可以增加一类的活性,也可以降低另一类的活性。总之,不同类别的 DNA 位点依赖性热点(其中有许多)对重组率的独立调节为减数分裂重组的全球频率分布的高度动态、大规模变化提供了分子机制。因为在裂殖酵母中发现的激活热点的 DNA 位点在其他物种中具有功能上的保守性,所以这个过程也可以解释以前神秘的、与 Prdm9 无关的、在密切相关的物种、亚种和同一物种的隔离种群之间热点使用的快速进化变化。