National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
PLoS One. 2013 Jun 25;8(6):e66817. doi: 10.1371/journal.pone.0066817. Print 2013.
Systematic determination of gene function is an essential step in fully understanding the precise contribution of each gene for the proper execution of molecular functions in the cell. Gene functional linkage is defined as to describe the relationship of a group of genes with similar functions. With thousands of genomes sequenced, there arises a great opportunity to utilize gene evolutionary information to identify gene functional linkages. To this end, we established a computational method (called TRACE) to trace gene footprints through a gene functional network constructed from 341 prokaryotic genomes. TRACE performance was validated and successfully tested to predict enzyme functions as well as components of pathway. A so far undescribed chromosome partitioning-like protein ro03654 of an oleaginous bacteria Rhodococcus sp. RHA1 (RHA1) was predicted and verified experimentally with its deletion mutant showing growth inhibition compared to RHA1 wild type. In addition, four proteins were predicted to act as prokaryotic SNARE-like proteins, and two of them were shown to be localized at the plasma membrane. Thus, we believe that TRACE is an effective new method to infer prokaryotic gene functional linkages by tracing evolutionary events.
系统地确定基因功能是充分了解每个基因在细胞内正确执行分子功能的精确贡献的必要步骤。基因功能关联被定义为描述一组具有相似功能的基因之间的关系。随着数千个基因组的测序，利用基因进化信息来识别基因功能关联有了很大的机会。为此，我们建立了一种计算方法（称为 TRACE），通过从 341 个原核基因组构建的基因功能网络来追踪基因足迹。TRACE 的性能经过验证，成功地用于预测酶功能以及途径的组成部分。一种迄今为止未被描述的油脂细菌 Rhodococcus sp. RHA1（RHA1）的染色体分区样蛋白 ro03654 被预测并通过缺失突变体实验验证，与 RHA1 野生型相比，其表现出生长抑制。此外，预测了四个蛋白质作为原核 SNARE 样蛋白，其中两个被证明位于质膜上。因此，我们相信 TRACE 是一种通过追踪进化事件推断原核基因功能关联的有效新方法。
