Genetics is one of the most complex and misunderstood areas of biology. In fact, scientists haven’t uncovered the functions of as much as one-third of genes in the genome of E. coli. A paper stemming from the University of California and published in the journal Cell discusses chemical genetics and its role in discovering biological systems in bacteria.

Chemical genetics is essentially the combination of pharmacology and genealogy. The study of genes involves analysis of mutations that are introduced into cells or organisms. Changes to the DNA or RNA take time to be transformed on the protein level, which is where the mutation can be fully observed. Due to the slow changes genetics places on an organism’s system, pharmacology is beneficial because pharmacological agents quickly and reversibly affects relevant targets.

In general, pharmacology seems to make up for some of the shortcomings of genetic analysis. The only possible limitation is the exclusive number of molecules with useful properties as compared to the more diverse target proteins of biology.

Chemical genetics is the study of changes in both DNA and small molecular structure or function. The paper goes into detail about two lead researchers that have attempted to identify cellular targets of vancomycin, a structurally complex product.

There have been many hypotheses about the potential targets of this antibiotic due to its chemical complexity. Synthetic versions of the antibiotic were made in the laboratory and genetic screenings were conducted on specific mutations. The researchers discovered mutations in the unannotated gene, yfgL. Prior to this, no genetic screenings have found any mutations in this particular gene.

A chemical genetic screen was able to show the mutation and the researchers extended the screen to determine how this was possible. The investigators included drug controls such as bile salts, vancomycin itself, and other molecules.

The results illustrate that yfgL is not the real target of the vancomycin complex but is part of several mutations that mute the effects of some antibiotics. It was also found that differing compounds of various structures could determine the toxicity of certain mutant strains.

The scientists also used immunoprecipitation trials to discover that yfgL is a component of a multiprotein complex in the outer membrane that is essentially needed for the creation of the outer membrane.

Within this study, chemical genetics was able to help uncover four proteins of previously unknown function working together in a complex outer membrane system. This system is able to assemble proteins outside of the bacterial cell wall without the use of ATP.

This research also shows how important small molecules are for natural evolution, as DNA, RNA, and proteins are not the only entities needed for a system to evolve. Clearly, pharmacology and chemical genetics play a significant role in scientific research and help to further our knowledge of biology.

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Categories: Toxicology and Pharmacology

Tags: chemical genetics, dna, genealogy, RNA