Gene synteny comparisons between different vertebrates provide new insights into breakage and fusion events during mammalian karyotype evolution
Gene synteny comparisons between different vertebrates provide new insights into breakage and fusion events during mammalian karyotype evolution
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DOI：
10.1186/1471-2148-9-84
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发表时间：
2009-04-24
影响因子：
3.4
通讯作者：
Kehrer-Sawatzki, Hildegard
中科院分区：
文献类型：
--
作者：
Kemkemer, Claus;Kohn, Matthias;Kehrer-Sawatzki, Hildegard
背景：基因组比较使真兽类祖先核型的重建成为可能，但也有可能为哺乳动物系统发育树中不同真兽目之间的进化相互关系提供新的见解。这样的比较还可以揭示(I)存在于进化断点区域内的DNA序列的性质，以及(Ii)进化断点是否在整个基因组中随机发生。基因同步性分析(E-PAINT)不仅大大降低了比较基因组序列分析的复杂性，而且扩展了其进化范围。结果：利用E-PAINT对6个不同哺乳动物物种和鸡的基因组序列进行了比较。总共确定了526个进化断点间隔，这些间隔被映射到120kb的中位数分辨率，这是迄今为止获得的最高分辨率水平。进化断点频率与基因密度之间存在显著的相关性。当比较长度短至40kb的基因组间隔时，这种相关性不仅在染色体水平上显着，而且在亚染色体水平上也显着。与之前的发现相反，将进化断点位置与图谱良好的常见脆性部位和癌症相关断点的染色体位置进行比较，未能揭示任何显著共定位的证据。然而，灵长类动物特有的染色体重排优先发生在包含节段重复和拷贝数变异的区域。结论：特定的染色体区域似乎容易在不同的哺乳动物谱系中反复重排(断点重复使用)，即使断点本身可能不相同。在对7种脊椎动物基因组序列进行共性分析的基础上，重建了祖先真兽类基因组，不仅证实了前人的分子细胞遗传学研究结果，而且增加了对祖先真兽类染色体推测结构的定义。在这样的分析中，负鼠第一次被列为外类群物种。这证实了我们之前的祖先真兽类基因组模型，因为所有祖先的同线节段关联也在这种有袋类动物中被记录下来。
Background: Genome comparisons have made possible the reconstruction of the eutherian ancestral karyotype but also have the potential to provide new insights into the evolutionary inter-relationship of the different eutherian orders within the mammalian phylogenetic tree. Such comparisons can additionally reveal (i) the nature of the DNA sequences present within the evolutionary breakpoint regions and (ii) whether or not the evolutionary breakpoints occur randomly across the genome. Gene synteny analysis (E-painting) not only greatly reduces the complexity of comparative genome sequence analysis but also extends its evolutionary reach.Results: E-painting was used to compare the genome sequences of six different mammalian species and chicken. A total of 526 evolutionary breakpoint intervals were identified and these were mapped to a median resolution of 120 kb, the highest level of resolution so far obtained. A marked correlation was noted between evolutionary breakpoint frequency and gene density. This correlation was significant not only at the chromosomal level but also sub-chromosomally when comparing genome intervals of lengths as short as 40 kb. Contrary to previous findings, a comparison of evolutionary breakpoint locations with the chromosomal positions of well mapped common fragile sites and cancer-associated breakpoints failed to reveal any evidence for significant co-location. Primate-specific chromosomal rearrangements were however found to occur preferentially in regions containing segmental duplications and copy number variants.Conclusion: Specific chromosomal regions appear to be prone to recurring rearrangement in different mammalian lineages ('breakpoint reuse') even if the breakpoints themselves are likely to be non-identical. The putative ancestral eutherian genome, reconstructed on the basis of the synteny analysis of 7 vertebrate genome sequences, not only confirmed the results of previous molecular cytogenetic studies but also increased the definition of the inferred structure of ancestral eutherian chromosomes. For the first time in such an analysis, the opossum was included as an outgroup species. This served to confirm our previous model of the ancestral eutherian genome since all ancestral syntenic segment associations were also noted in this marsupial.