Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes
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DOI：
10.1101/gr.3715005
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发表时间：
2005-08-01
期刊：
影响因子：
7
通讯作者：
Haussler, D
中科院分区：
文献类型：
--
作者：
Siepel, A;Bejerano, G;Haussler, D
我们已经进行了一个全面的搜索在脊椎动物基因组中的保守元件，使用全基因组的多重比对的五种脊椎动物物种（人，小鼠，大鼠，鸡，和红鳍东方）。平行搜索已经进行了多重比对的四种昆虫（果蝇和冈比亚按蚊的三个物种），两个物种的小杆线虫，和7种酵母菌。保守的元素被称为phastCons，这是基于一个两个状态的系统发育隐马尔可夫模型（HMM）的计算机程序进行了鉴定。PhastCons的工作原理是通过最大似然法将一个R-HMM拟合到数据中，受到设计用于跨物种组校准模型的约束，然后基于该模型预测保守元素。预测的元件覆盖了大约3%-8%的人类基因组（取决于校准程序的细节），以及更紧凑的黑腹果蝇（37%-53%），秀丽隐杆线虫（18%-37%）和酿酒酵母（47%-68%）基因组的更高比例。从酵母到脊椎动物，按照基因组大小和一般生物学复杂性增加的顺序，发现越来越多的保守碱基部分位于已知蛋白质编码基因的外显子之外。在所有组中，最高度保守的元件（HCE），通过对数几率得分，是数百或数千个碱基长。这些元件与超保守元件具有某些共同特性，但它们往往更长，保守性更差，并且它们与功能类别略有不同的基因重叠。在脊椎动物中，HCE与调节基因的3'UTR、稳定基因沙漠和富含适度保守非编码序列的兆碱基大小的区域相关。非编码HCE也显示了RNA二级结构的所有富集的强有力的统计学证据。
We have conducted a comprehensive search for conserved elements in vertebrate genomes, using genome-wide Multiple alignments of five vertebrate species (human, Mouse, rat, chicken, and Fugu rubripes). Parallel searches have been performed with multiple alignments Of four insect species (three species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model (phylo-HMM). PhastCons works by fitting a phylo-HMM to the data by maximum likelihood, Subject to constraints designed to calibrate the model across species groups, and then predicting conserved elements based oil this model. The predicted elements cover roughly 3%-8% of the human genome (depending on the details of the calibration procedure) and Substantially higher fractions of the more compact Drosophila melanogaster (37%-53%), Caenorhabditis elegans (18%-37%), and Saccharaomyces cerevisiae (47%-68%) genomes. From yeasts to vertebrates, in order of increasing genome size and general biological complexity, increasing fractions of conserved bases are found to lie Outside of the exons of known protein-coding genes. In all groups, the most highly conserved elements (HCEs), by log-odds score, are hundreds or thousands of bases long. These elements share certain properties With Ultraconserved elements, but they tend to be longer and less perfectly conserved, and they overlap genes of somewhat different functional categories. In vertebrates, HCEs are associated with the 3' UTRs of regulatory genes, stable gene deserts, and megabase-sized regions rich in moderately conserved noncoding sequences. Noncoding HCEs also show strong statistical evidence of ail enrichment for RNA secondary structure.