Mutant phenotypes for thousands of bacterial genes of unknown function

Mutant phenotypes for thousands of bacterial genes of unknown function
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DOI:
10.1038/s41586-018-0124-0
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发表时间:
2018-05-24
期刊:
影响因子:
64.8
通讯作者:
Deutschbauer, Adam M.
Deutschbauer, Adam M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Price, Morgan N.;Wetmore, Kelly M.;Deutschbauer, Adam M.

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来自细菌基因组的所有蛋白质编码基因中有三分之一无法用功能注释。在这里,为了研究这些基因的功能,我们提出了来自32种不同细菌在几十种生长条件下的全基因组突变体适应性数据。我们确定了11,779个蛋白质编码基因的突变表型,这些基因尚未被注释为特定功能。许多基因可能与特定条件相关,因为该基因只在该条件下影响适应性,或者与同一细菌中的另一个基因相关,因为它们具有相似的突变表型。在注释不佳的基因中,有2,316个具有高置信度的关联,因为它们在其他细菌中是保守的。通过将这些保守的关联与比较基因组学相结合,我们确定了推定的DNA修复蛋白;此外,我们提出了注释不佳的酶和转运蛋白以及未表征的蛋白质家族的特定功能。我们的研究证明了微生物遗传学的可扩展性及其在改善基因注释方面的实用性。
One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes. Of the poorly annotated genes, 2,316 had associations that have high confidence because they are conserved in other bacteria. By combining these conserved associations with comparative genomics, we identified putative DNA repair proteins; in addition, we propose specific functions for poorly annotated enzymes and transporters and for uncharacterized protein families. Our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.