Identification and characterization of new long conserved noncoding sequences in vertebrates
Identification and characterization of new long conserved noncoding sequences in vertebrates
复制标题
DOI：
10.1007/s00335-008-9152-7
复制
发表时间：
2008-12-01
期刊：
影响因子：
2.5
通讯作者：
Gondo, Yoichi
中科院分区：
文献类型：
--
作者：
Sakuraba, Yoshiyuki;Kimura, Toru;Gondo, Yoichi
比较序列分析已经确定了人类和其他物种之间高度保守的基因组DNA序列，包括非编码序列。通过对人类和小鼠的全基因组比较，我们鉴定出611条长度大于500 bp的保守非编码序列，物种之间的同源性超过95%。这些长保守非编码序列（LCNS）包括473个与先前报道的超保守元件（UCE）不重叠的新序列，UCE被定义为长度超过200 bp的序列，在人类，小鼠和大鼠中具有100%的同源性。LCNS分布在除Y染色体外的整个基因组中，并且经常聚集在编码基因密度低的区域内。许多LCNS在其他哺乳动物、鸡、青蛙和鱼中也高度保守；然而，我们无法在无脊椎动物物种的基因组中找到同源序列。为了检验这些保守序列是否具有重要的功能或仅仅是突变的冷点，我们直接测量了enu诱导的小鼠LCNS种系突变的频率。通过筛选约40.7 Mb，我们发现了35个突变，包括在人类和鱼类之间保守的核苷酸突变。突变频率与其他基因组区域（包括编码序列和内含子）的突变频率相同，这表明LCNS根本不是突变冷点。综上所述，这些结果表明，突变在LCNS中以相同的频率发生，但在进化过程中被自然选择消除。
Comparative sequence analyses have identified highly conserved genomic DNA sequences, including noncoding sequences, between humans and other species. By performing whole-genome comparisons of human and mouse, we have identified 611 conserved noncoding sequences longer than 500 bp, with more than 95% identity between the species. These long conserved noncoding sequences (LCNS) include 473 new sequences that do not overlap with previously reported ultraconserved elements (UCE), which are defined as aligned sequences longer than 200 bp with 100% identity in human, mouse, and rat. The LCNS were distributed throughout the genome except for the Y chromosome and often occurred in clusters within regions with a low density of coding genes. Many of the LCNS were also highly conserved in other mammals, chickens, frogs, and fish; however, we were unable to find orthologous sequences in the genomes of invertebrate species. In order to examine whether these conserved sequences are functionally important or merely mutational cold spots, we directly measured the frequencies of ENU-induced germline mutations in the LCNS of the mouse. By screening about 40.7 Mb, we found 35 mutations, including mutations at nucleotides that were conserved between human and fish. The mutation frequencies were equivalent to those found in other genomic regions, including coding sequences and introns, suggesting that the LCNS are not mutational cold spots at all. Taken together, these results suggest that mutations occur with equal frequency in LCNS but are eliminated by natural selection during the course of evolution.