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a combination of cis and trans control can solve the hotspot conversion paradox


作者單位:Department of Zoology and Center of Rapid Evolution, University of Wisconsin, Madison, Wisconsin 537061 Address for correspondence: Department of Zoology, Birge Hall, 430 Lincoln Dr., University of Wisconsin, Madison, WI 53706.

【摘要】 there is growing evidence that in a variety of organisms the majority of meiotic recombination events occur at a relatively small fraction of loci, known as recombination hotspots. if hotspot activity results from the dna sequence at or near the hotspot itself (in cis ), these hotspots are expected to be rapidly lost due to biased gene conversion, unless there is strong selection in favor of the hotspot itself. this phenomenon makes it very difficult to maintain existing hotspots and even more difficult for new hotspots to evolve; it has therefore come to be known as the "hotspot conversion paradox." i develop an analytical framework for exploring the evolution of recombination hotspots under the forces of selection, mutation, and conversion. i derive the general conditions under which cis- and trans -controlled hotspots can be maintained, as well as those under which new hotspots controlled by both a cis and a trans locus can invade a population. i show that the conditions for maintenance of and invasion by trans - or cis -plus- trans -controlled hotspots are broader than for those controlled entirely in cis. finally, i show that a combination of cis and trans control may allow for long-lived polymorphisms in hotspot activity, the patterns of which may explain some recently observed features of recombination hotspots.

【關鍵詞】 combination conversion


there is growing evidence from several model systems across the eukaryotic phylogeny that meiotic recombination events, rather than being distributed uniformly across the genome, are largely concentrated into relatively small regions known as "recombination hotspots." hotspots in yeast ( m alone et al. 1994; w u and l ichten 1995; p etes 2001; c romie et al. 2005 ), mice ( g uillon and d e m assy 2002; k elmenson et al. 2005; s hifman et al. 2006; b audat and d e m assy 2007 ), and humans ( j effreys et al. 1998, 2000, 2001, 2005; c rawford et al. 2004; m c v ean et al. 2004; m yers et al. 2005; c onrad et al. 2006; i nternational h ap m ap c onsortium 2007 ) have now been well characterized, and evidence suggests that hotspots also exist in chimpanzees ( p tak et al. 2005 ) and several plants ( d ooner and m artinez -f erez 1997; o kagaki and w eil 1997; y ao et al. 2002; d rouaud et al. 2006 ). while some other well-studied eukaryotes ( e.g., drosophila melanogaster and caenorhabditis elegans ) show no evidence of hotspots ( h ey 2004 ), the phenomenon is widespread enough across the tree of life to merit substantial study.

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