Intraspecies sequence comparisons for annotating genomes
Intraspecies sequence comparisons for annotating genomes
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DOI：
10.1101/gr.3199704
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发表时间：
2004-12-01
期刊：
影响因子：
7
通讯作者：
Rubin, EM
中科院分区：
文献类型：
--
作者：
Boffelli, D;Weer, CV;Rubin, EM
单一物种成员之间的序列变异分析提供了一种潜在的方法，以确定负责该物种独特的生物学特征的功能DNA元件。由于其等位基因多态性的高比率和易于遗传操作，我们选择了海鞘，戈纳鞘，探索种内序列比较基因组注释。大量的C。从四大洲收集了一组基因组间隔，对它们进行扩增、重测序和分析，以确定序列中每个核苷酸的突变率。我们发现，低突变率的区域有效地划分了功能受限的序列：这些序列包括一组非编码元件，我们在C.利用转基因检测法确定其作为组织特异性增强子的作用，以及编码序列的位置。这表明，一个物种的多个成员的比较可以用于基因组注释，这表明了一个路径的生物体的测序基因组的注释占据动物王国的未表征的系统发育分支。它还提出了一种可能性，即对大量智人个体进行重新测序可能被用来注释人类基因组，并确定定义我们物种独特特征的序列。
Analysis of sequence variation among members of a single species offers a potential approach to identify functional DNA elements responsible for biological features unique to that species. Due to its high rate of allelic polymorphism and ease of genetic manipulability, we chose the sea squirt, Gona intestinalis, to explore intraspecies sequence comparisons for genome annotation. A large number of C. intestinalis specimens were collected from four continents, and a set of genomic intervals were amplified, resequenced, and analyzed to determine the mutation rates at each nucleotide in the sequence. We found that regions with low mutation rates efficiently demarcated functionally constrained sequences: these include a set of noncoding elements, which we showed in C. intestinalis transgenic assays to act as tissue-specific enhancers, as well as the location of coding sequences. This illustrates that comparisons of multiple members of a species can be used for genome annotation, suggesting a path for the annotation of the sequenced genomes of organisms occupying uncharacterized phylogenetic branches of the animal kingdom. It also raises the possibility that the resequencing of a large number of Homo sapiens individuals might be used to annotate the human genome and identify sequences defining traits unique to our species.