Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12378-83. doi: 10.1073/pnas.1109531108. Epub 2011 Jul 12.
PRDM9 is a major specifier of human meiotic recombination hotspots, probably via binding of its zinc-finger repeat array to a DNA sequence motif associated with hotspots. However, our view of PRDM9 regulation, in terms of motifs defined and hotspots studied, has a strong bias toward the PRDM9 A variant particularly common in Europeans. We show that population diversity can reveal a second class of hotspots specifically activated by PRDM9 variants common in Africans but rare in Europeans. These African-enhanced hotspots nevertheless share very similar properties with their counterparts activated by the A variant. The specificity of hotspot activation is such that individuals with differing PRDM9 genotypes, even within the same population, can use substantially if not completely different sets of hotspots. Each African-enhanced hotspot is activated by a distinct spectrum of PRDM9 variants, despite the fact that all are predicted to bind the same sequence motif. This differential activation points to complex interactions between the zinc-finger array and hotspots and identifies features of the array that might be important in controlling hotspot activity.
PRDM9 是人类减数分裂重组热点的主要决定因素,可能通过其锌指重复序列阵列与与热点相关的 DNA 序列基序结合来实现。然而,我们对 PRDM9 调控的看法,就定义的基序和研究的热点而言,强烈偏向于 PRDM9 A 变体,这种变体在欧洲人中特别常见。我们表明,群体多样性可以揭示第二类热点,这些热点特别由非洲常见但在欧洲罕见的 PRDM9 变体激活。这些非洲增强型热点与由 A 变体激活的热点具有非常相似的特性。热点激活的特异性使得具有不同 PRDM9 基因型的个体,即使在同一人群中,也可以使用大量(如果不是完全不同的)热点。尽管所有这些热点都被预测与相同的序列基序结合,但每个非洲增强型热点都由不同的 PRDM9 变体激活。这种差异激活表明锌指阵列和热点之间存在复杂的相互作用,并确定了阵列中可能对控制热点活性很重要的特征。