A small reservoir of disabled ORFs in the yeast genome and its implications for the dynamics of proteome evolution
A small reservoir of disabled ORFs in the yeast genome and its implications for the dynamics of proteome evolution
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DOI：
10.1006/jmbi.2001.5343
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发表时间：
2002-02-22
影响因子：
5.6
通讯作者：
Gerstein, M
中科院分区：
文献类型：
--
作者：
Harrison, P;Kumar, A;Gerstein, M
我们全面调查了已测序的酿酒酵母基因组（菌株 S288C）的开放阅读框（ORF），这些开放阅读框可以编码全长蛋白质，但包含明显的中序列缺陷（移码或过早终止密码子）。这些假基因特征被称为禁用 ORF (dORF)。利用与注释的酵母 ORF 和非酵母蛋白的同源性加上简单的区域延伸程序，我们发现了 183 个 dORF。结合潜在 dORF 的 38 个现有注释，我们总共拥有多达 221 个 dORF，相当于不到 3% 的蛋白质组。此外，我们发现了 20 对带注释的酵母 ORF，它们可以通过通读插入的终止密码子合并成单个 ORF（称为 mORF），并且可能在其他酵母菌株中包含完整的 ORF。着眼于具有验证蛋白质同源性的 98 个 dORF 的核心库，我们发现大多数 dORF 都已严重衰退，大约 90% 的 dORF 具有两个或更多的功能障碍，大约 60% 的 dORF 具有四个或更多的功能。 dORF 比活酵母基因更具酵母蛋白质组特异性（它们与非酵母蛋白质相关的可能性约为一半）。相对于基因，它们显示染色体端粒的密度显着增加。一项微阵列研究表明，一些 dORF 即使携带多种功能障碍也会被表达，因此可能对无义介导的衰变具有更强的抵抗力。许多 dORF 可能参与对环境应激的响应，因为最大的功能组包括生长抑制、絮凝和 SRP/TIP1 家族。我们的结果对蛋白质组进化具有重要意义。 dORF群体的特征表明了可能以菌株特异性方式使用和不再使用的基因类型（并且拷贝数不同），并强调了亚端粒区域在产生这种多样性中的作用。我们的结果对于 [PSI+] 朊病毒的影响也具有重要意义。仅被一个终止点禁用的 dORF 和 mORF（总共 35 个）提供了对序列群体范围的估计，该序列群体可以通过 [PSI+] 朊病毒引起无义密码子通读的能力轻易地复活。此外，我们发现的 dORF 和 mORF 具有的特性（例如生长抑制、絮凝、钒酸盐抗性、应激反应）可能与 [PSI+] 在不同环境条件下在酵母菌株中产生显着表型变异的能力有关。 （请参阅genecensus.org/pseudogene 了解更多信息。） (C) 2002 Elsevier Science Ltd.
We surveyed the sequenced Saccharomyces cerevisiae genome (strain S288C) comprehensively for open reading frames (ORFs) that could encode full-length proteins but contain obvious mid-sequence disablements (frameshifts or premature stop codons). These pseudogenic features are termed disabled ORFs (dORFs). Using homology to annotated yeast ORFs and non-yeast proteins plus a simple region extension procedure, we have found 183 dORFs. Combined with the 38 existing annotations for potential dORFs, we have a total pool of up to 221 dORFs, corresponding to less than similar to3% of the proteome. Additionally, we found 20 pairs of annotated ORFs for yeast that could be merged into a single ORF (termed a mORF) by read-through of the intervening stop codon, and may comprise a complete ORF in other yeast strains. Focussing on a core pool of 98 dORFs with a verifying protein homology, we find that most dORFs are substantially decayed, with similar to90% having two or more disablements, and similar to60% having four or more. dORFs are much more yeast-proteome specific than live yeast genes (having about half the chance that they are related to a non-yeast protein). They show a dramatically increased density at the telomeres of chromosomes, relative to genes. A microarray study shows that some dORFs are expressed even though they carry multiple disablements, and thus may be more resistant to nonsense-mediated decay. Many of the dORFs may be involved in responding to environmental stresses, as the largest functional groups include growth inhibition, flocculation, and the SRP/TIP1 family. Our results have important implications for proteome evolution. The characteristics of the dORF population suggest the sorts of genes that are likely to fall in and out of usage (and vary in copy number) in a strain-specific way and highlight the role of subtelomeric regions in engendering this diversity. Our results also have important implications for the effects of the [PSI+] prion. The dORFs disabled by only a single stop and the mORFs (together totalling 35) provide an estimate for the extent of the sequence population that can be resurrected readily through the demonstrated ability of the [PSI+] prion to cause nonsense-codon read-through. Also, the dORFs and mORFs that we find have properties (e.g. growth inhibition, flocculation, vanadate resistance, stress response) that are potentially related to the ability of [PSI+] to engender substantial phenotypic variation in yeast strains under different environmental conditions. (See genecensus.org/pseudogene for further information.) (C) 2002 Elsevier Science Ltd.