Assessing the genomic evidence for conserved transcribed pseudogenes under selection.
Assessing the genomic evidence for conserved transcribed pseudogenes under selection.
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DOI：
10.1186/1471-2164-10-435
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发表时间：
2009-09-15
期刊：
影响因子：
4.4
通讯作者：
Harrison PM
中科院分区：
文献类型：
--
作者：
Khachane AN;Harrison PM
转录的假基因是蛋白质编码基因的拷贝，这些基因积累了编码序列衰变的指标（如移码和过早的终止密码子），但仍然保持转录。最近的实验证据表明，转录的假基因可以通过反义干扰或产生小干扰RNA（siRNA）来调节同源基因的表达。在这里，我们评估了在人类基因组中这些转录的具有潜在功能重要性的假基因的基因组证据。这种功能重要性的最明显的指标是保护和选择压力的重要证据。汇集并过滤来自多个来源的各种假基因注释，以获得具有显著的中间序列失能（移码和过早终止密码子）并且具有全长mRNA转录的明确证据的序列子集。我们在人类基因组中发现了1750个这样的转录假基因注释（TPAs）（相当于人类假基因注释的~11.5%）。我们检查了其他哺乳动物（恒河猴、小鼠、大鼠、狗和牛）中TPA的同线保护。大约一半的人TPA在恒河猴中是保守的，但引人注目的是，在小鼠中非常少（~3%）。在恒河猴中保守的TPA显示出选择压力（相对于周围的基因间DNA）的证据：（i）它们的GC含量，和（ii）它们的核苷酸取代率。尽管Ka/Ks（非同义与同义置换率的比率）的分布与缺乏蛋白质编码能力一致。此外，我们已经确定了68人TPA的syntenically保守在至少两个其他哺乳动物。有趣的是，我们观察到在狗中保守的三个TPA序列具有中间特征（即，证据的蛋白质编码能力和pseudogenicity），并讨论这一点的影响。通过进化分析，我们已经确定了候选序列的功能性人类转录的假基因，并确定了68个强有力的候选人进一步调查的潜在功能性转录的假基因在多个哺乳动物物种。
Transcribed pseudogenes are copies of protein-coding genes that have accumulated indicators of coding-sequence decay (such as frameshifts and premature stop codons), but nonetheless remain transcribed. Recent experimental evidence indicates that transcribed pseudogenes may regulate the expression of homologous genes, through antisense interference, or generation of small interfering RNAs (siRNAs). Here, we assessed the genomic evidence for such transcribed pseudogenes of potential functional importance, in the human genome. The most obvious indicators of such functional importance are significant evidence of conservation and selection pressure. A variety of pseudogene annotations from multiple sources were pooled and filtered to obtain a subset of sequences that have significant mid-sequence disablements (frameshifts and premature stop codons), and that have clear evidence of full-length mRNA transcription. We found 1750 such transcribed pseudogene annotations (TPAs) in the human genome (corresponding to ~11.5% of human pseudogene annotations). We checked for syntenic conservation of TPAs in other mammals (rhesus monkey, mouse, rat, dog and cow). About half of the human TPAs are conserved in rhesus monkey, but strikingly, very few in mouse (~3%). The TPAs conserved in rhesus monkey show evidence of selection pressure (relative to surrounding intergenic DNA) on: (i) their GC content, and (ii) their rate of nucleotide substitution. This is in spite of distributions of Ka/Ks (ratios of non-synonymous to synonymous substitution rates), congruent with a lack of protein-coding ability. Furthermore, we have identified 68 human TPAs that are syntenically conserved in at least two other mammals. Interestingly, we observe three TPA sequences conserved in dog that have intermediate character (i.e., evidence of both protein-coding ability and pseudogenicity), and discuss the implications of this. Through evolutionary analysis, we have identified candidate sequences for functional human transcribed pseudogenes, and have pinpointed 68 strong candidates for further investigation as potentially functional transcribed pseudogenes across multiple mammal species.
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影响因子：
3.4
作者：
Brocchieri L;Conway de Macario E;Macario AJ
通讯作者：
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影响因子：
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