跨测序微生物的遗传共现网络
Genetic Co-Occurrence Network across Sequenced Microbes
摘要：
地球上任何生物的表型在很大程度上都是基因组中编码的众多基因产物之间相互作用的结果，基因产物之间的这种相互作用通过所产生的表型影响基因组本身的进化命运。在这方面，当代基因组可以用作分子记录，揭示在自然生活方式中工作的各种基因的关联。通过分析约600种细菌的数千个直系同源物，我们构建了一个基因-基因共现图，跨越了大部分测序的生物群系。如果基因优先在同一生物体中共存，则在此称为correlogs;在相反的情况下，称为anti-correlogs。为了量化相关性和反相关性，我们通过调整为转录调控网络的反向工程开发的想法来减轻基因之间的间接相关性的贡献。所产生的correcting协会是高度丰富的物理相互作用的蛋白质和共表达的成绩单，明确区分功能强制性蛋白质相互作用的亚组从条件或短暂的相互作用。其他生化和系统发育特性也被发现反映在相关和反相关关系。此外，我们的研究阐明了基因关联图的全局组织，其中相关基因的各个模块通过模块之间的反相关串扰惊人地相互连接。然后，我们证明了这种协会沿着不同领域的生活和环境微生物群落的有效性。这些系统发育分析方法推断功能耦合的基因，而不管机制的细节，并可能是有用的，以指导外源基因导入合成生物学。
英文摘要：
The phenotype of any organism on earth is, in large part, the consequence of interplay between numerous gene products encoded in the genome, and such interplay between gene products affects the evolutionary fate of the genome itself through the resulting phenotype. In this regard, contemporary genomes can be used as molecular records that reveal associations of various genes working in their natural lifestyles. By analyzing thousands of orthologs across ~600 bacterial species, we constructed a map of gene-gene co-occurrence across much of the sequenced biome. If genes preferentially co-occur in the same organisms, they were called herein correlogs; in the opposite case, called anti-correlogs. To quantify correlogy and anti-correlogy, we alleviated the contribution of indirect correlations between genes by adapting ideas developed for reverse engineering of transcriptional regulatory networks. Resultant correlogous associations are highly enriched for physically interacting proteins and for co-expressed transcripts, clearly differentiating a subgroup of functionally-obligatory protein interactions from conditional or transient interactions. Other biochemical and phylogenetic properties were also found to be reflected in correlogous and anti-correlogous relationships. Additionally, our study elucidates the global organization of the gene association map, in which various modules of correlogous genes are strikingly interconnected by anti-correlogous crosstalk between the modules. We then demonstrate the effectiveness of such associations along different domains of life and environmental microbial communities. These phylogenetic profiling approaches infer functional coupling of genes regardless of mechanistic details, and may be useful to guide exogenous gene import in synthetic biology.
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