Loose ends: almost one in five human genes still have unresolved coding status
Loose ends: almost one in five human genes still have unresolved coding status
复制标题
DOI：
10.1093/nar/gky587
复制
发表时间：
2018-08-21
影响因子：
14.9
通讯作者：
Tress, Michael L.
中科院分区：
文献类型：
--
作者：
Abascal, Federico;Juan, David;Tress, Michael L.
人类基因组测序十七年后，人类蛋白质组仍在修订中。 Ensembl/GENCODE、RefSeq 和 UniProtKB 参考数据库列出的 22 210 个编码基因中，八分之一的基因在这三组中的注释不同。我们对2764个基因进行了深入调查，这些基因被归类为由一组或多组手动管理者编码而不是由其他人编码。来自大规模遗传变异分析的数据表明，大多数没有经过类似蛋白质的纯化选择，因此不太可能编码功能性蛋白质。在所有三个参考集中注释为编码的另外 1470 个基因具有非编码基因或假基因的典型特征。这些潜在的非编码基因似乎也正在经历中性进化，并且与其他编码基因相比，支持转录物和蛋白质的证据要少得多。我们认为，三个参考数据库目前高估了人类编码基因的数量至少 2000 个，使大规模生物医学实验变得复杂化并增加了噪音。确定哪些潜在的非编码基因不编码蛋白质是一项困难但至关重要的任务，因为人类参考蛋白质组是大多数基础研究的基本支柱，并支持几乎所有大型生物医学项目。
Seventeen years after the sequencing of the human genome, the human proteome is still under revision. One in eight of the 22 210 coding genes listed by the Ensembl/GENCODE, RefSeq and UniProtKB reference databases are annotated differently across the three sets. We have carried out an in-depth investigation on the 2764 genes classified as coding by one or more sets of manual curators and not coding by others. Data from large-scale genetic variation analyses suggests that most are not under protein-like purifying selection and so are unlikely to code for functional proteins. A further 1470 genes annotated as coding in all three reference sets have characteristics that are typical of non-coding genes or pseudogenes. These potential non-coding genes also appear to be undergoing neutral evolution and have considerably less supporting transcript and protein evidence than other coding genes. We believe that the three reference databases currently overestimate the number of human coding genes by at least 2000, complicating and adding noise to large-scale biomedical experiments. Determining which potential non-coding genes do not code for proteins is a difficult but vitally important task since the human reference proteome is a fundamental pillar of most basic research and supports almost all large-scale biomedical projects.