Population-specific differences in gene conversion patterns between human SUZ12 and SUZ12P are indicative of the dynamic nature of interparalog gene conversion
Population-specific differences in gene conversion patterns between human SUZ12 and SUZ12P are indicative of the dynamic nature of interparalog gene conversion
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DOI：
10.1007/s00439-013-1410-4
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发表时间：
2014-04-01
期刊：
影响因子：
5.3
通讯作者：
Kehrer-Sawatzki，Hildegard
中科院分区：
文献类型：
--
作者：
Mussotter，Tanja;Bengesser，Kathrin;Kehrer-Sawatzki，Hildegard
非等位同源基因转换(NAHGC)是由无交叉的平行序列间重组产生的，对人类基因组中重复序列的进化具有重要的影响。在17q11.2中，不同的平行序列通过与交换(Nahr)的非等位同源重组(Nahr)来介导大的NF1缺失。其中SUZ12及其假基因SUZ12P含有NF1缺失类型2(1.2-Mb)的断裂点。这种缺失主要是由有丝分裂的Nahr引起的，因为在大多数患者中，正常细胞的体细胞嵌合体是明显的。在调查SUZ12和SUZ12P是否也参与NAHGC时，我们观察到这些近亲之间的基因转换区在非洲人(AFR)和欧洲人(EUR)之间。由于由Nahr减数分裂导致的生殖系2NF1缺失非常罕见，因此SUZ12和SUZ12P中的绝大多数基因转换区可能是生殖细胞减数分裂前细胞分裂过程中有丝分裂重组的结果。与EUR相比，SUZ12和SUZ12Pin AFR中的基因转换区数目较多。此外，NAHGC的独特特征(每个Paralog有大量SNPs，Paralog之间有大量共享SNP)，这是许多活跃重组Paralog的特征，但仅在AFR中观察到，而在EUR中没有观察到。在SUZ12P中发现了一个新的2.3kb的多态缺失，该缺失在EUR中具有很高的等位基因频率。我们推测，这种平行序列间的结构差异，加上低的等位基因重组率，可能导致在人类进化过程中SUZ12和SUZ12P之间的NAHGC减少。
Nonallelic homologous gene conversion (NAHGC) resulting from interparalog recombination without crossover represents an important influence on the evolution of duplicated sequences in the human genome. In 17q11.2, different paralogous sequences mediate largeNF1deletions by nonallelic homologous recombination with crossover (NAHR). Among these paralogs areSUZ12and its pseudogeneSUZ12Pwhich harbour the breakpoints of type-2 (1.2-Mb)NF1deletions. Such deletions are caused predominantly by mitotic NAHR since somatic mosaicism with normal cells is evident in most patients. Investigating whetherSUZ12andSUZ12Phave also been involved in NAHGC, we observed gene conversion tracts between these paralogs in both Africans (AFR) and Europeans (EUR). Since germline type-2NF1deletions resulting from meiotic NAHR are very rare, the vast majority of the gene conversion tracts inSUZ12andSUZ12Pare likely to have resulted from mitotic recombination during premeiotic cell divisions of germ cells. A higher number of gene conversion tracts were noted withinSUZ12andSUZ12Pin AFR as compared to EUR. Further, the distinctive signature of NAHGC (a high number of SNPs per paralog and a high number of shared SNPs between paralogs), a characteristic of many actively recombining paralogs, was observed in bothSUZ12andSUZ12Pbut only in AFR and not in EUR. A novel polymorphic 2.3-kb deletion inSUZ12Pwas identified which exhibited a high allele frequency in EUR. We postulate that this interparalog structural difference, together with low allelic recombination rates, could have caused a reduction in NAHGC betweenSUZ12andSUZ12Pduring human evolution.