NIH Research Festival
Understanding the organization and conservation of essential genes is critical for basic and applied biomedical research. Here we integrated a set of 17 high-resolution and genome-wide experimental in vitro essential gene studies and three in vivo required gene datasets, encompassing 15 bacteria and one Archaea. We assessed the overall features of essential genes in these two domains of life and demonstrated that most indispensable genes share important genomic architecture features, conservation and functional patterns among all species, possibly reflecting characteristics of an ancestral life form. Essential genes tend to be monogenic and are more conserved than nonessential genes. In contrast, genes particularly critical in vivo tend to be less conserved than those essential in vitro, suggesting that distinct strategies are deployed when the organism is stressed by the host immune system and unstable nutrient availability. Integration of evolutionary conservation and dispensability data allowed the identification of condition-specific novel gene targets with potential roles in the infection process of Mycobacterium tuberculosis and Burkholderia pseudomallei. Moreover, essential genes are not only preferentially located in operons, but are also biased toward the first position of the operons, supporting the influence of their regulatory regions in driving the transcription of whole operons. Finally, we demonstrated that the essential gene sets of Bacteria and an Archaea share important genomic features, indicating that high order properties of gene essentiality and genome architecture were probably present in the last universal common ancestor or evolved independently in the two prokaryotic domains of life.
Scientific Focus Area: Computational Biology
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