Academic journal article Genetics

An Essential Regulatory System Originating from Polygenic Transcriptional Rewiring of PhoP-PhoQ of Xanthomonas Campestris

Academic journal article Genetics

An Essential Regulatory System Originating from Polygenic Transcriptional Rewiring of PhoP-PhoQ of Xanthomonas Campestris

Article excerpt

ESSENTIAL genes play critical roles in the vitality of an organism, such as in cell division, macromolecule synthesis, ribosome assembly, and embryo development. Genetic inactivation of these genes leads to lethality or infertility (Wilson et al 1977). Consequently, null mutations in essential genes would be promptly erased by the overwhelming force of purifying selection (Jordan et al. 2002; Bergmiller et al. 2012). Based on this, it was predicted that essential genes would evolve much slower than nonessential genes. However, recent theoretical and experimental studies have revealed that essential genes can also originate from novel genes during speciation, implying that the molecular mechanisms determining the origins of essential genes are diverse (Hurst and Smith 1999; Chen etai. 2010). Among them, the evolution of essential, regulatory genes is more intriguing, since they modulate the expression of various downstream genes, which complicates the evolutionary impact of mutations in these regulatory genes. However, to date, how essential, regulatory genes originate and evolve remains largely unclear (Peter and Davidson 2011; Harms and Thornton 2013).

One of the difficulties in studying the evolution of essential regulatory genes is that the biological functions of these genes depend substantially on the genetic context during regulation and growth conditions of the organism (D'Elia et al. 2009). In fact, the theoretical prediction of which regulatory gene is essential perse is a challenge. For example, a number of genes that are essential in one organism have been experimentally confirmed to be nonessential in closely related organisms (Dussurget et al 1996; Rodriguez et al. 2002; Ng et al. 2004; Bisicchia et al. 2007). Bioinformatic studies that predicted essential regulatory genes merely through homology searching inevitably introduced bias by including nonessential genes or ignoring the genetic context of the regulatory genes in the analyses. Even in genome-wide mutational studies, the failure to obtain a viable gene mutant is also weak evidence to support the essentiality of the gene. For instance, in bacteria, the polar effect of an insertional mutation within an operon and the growth conditions complicate the subsequent genetic analysis (Glass et al. 2006; Xu et al. 2011). Furthermore, the evolution of the biological function of regulatory genes may not be caused by genetic polymorphisms in themselves but instead may be determined by their downstream genes or even their mode of molecular regulation. Therefore, to solve these problems, a "bottom-up" strategy, which dissects the evolutionary changes in the complete regulatory cascade based on genetic and biochemical analyses, would not only avoid the problematic prediction of essential regulatory genes but could also reconstruct the possible molecular steps of genetic variations during their evolution (Perez and Groisman 2009a; Harms and Thornton 2013). Together with theoretical studies, a more complete view of the origin of essential regulatory genes could be achieved by multidisciplinary investigations.

In prokaryotes, PhoP-PhoQ represents a typical twocomponent signal transduction system (TCS), which is the predominant sense-and-response mechanism that is usually compared with the "nervous system" of eukaryotic cells (Goulian 2010). PhoP-PhoQ is also one of the most extensively studied signaling systems in all organisms (Groisman 2001; Ohl and Miller 2001). PhoQ is an inner membrane-bound receptor histidine kinase (HK). After detecting environmental signals of Mg2+, Ca2+, low pH, or cationic antimicrobial peptides, PhoQ activates its autokinase activity by phosphorylating a conserved histidine residue (His) and then transfers the phosphoryl group to PhoP, a cytosolic response regulator (RR) with transcription factor activity. Eventually, the activated PhoP modulates the transcription of downstream genes by binding directly to their cis-regulatory elements (CREs) (Kato and Groisman 2008; Prost and Miller 2008). …

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