Organisms with alternative genetic codes resolve unassigned codons via mistranslation and ribosomal rescue

摘要

Usually, DNA passes from parent to offspring, vertically down the generations. But not always. In some cases, it can move directly from one organism to another by a process called horizontal gene transfer. In bacteria, this happens when DNA segments pass through a bacterium’s cell wall, which can then be picked up by another bacterium. Because the vast majority of organisms share the same genetic code, the bacteria can read this DNA with ease, as it is in the same biological language. Horizontal gene transfer helps bacteria adapt and evolve to their surroundings, letting them swap and share genetic information that could be useful. The process also poses a threat to human health because the DNA that bacteria share can help spread antibiotic resistance. However, some organisms use an alternative genetic code, which obstructs horizontal gene transfer. They cannot read the DNA transmitted to them, because it is in a different ‘biological language’. The mechanism of how this language barrier works has been poorly understood until now. Ma, Hemez, Barber et al. investigated this using Escherichia coli bacteria with an artificially alternated genetic code. In this E. coli, one of the three-letter DNA ‘words’ in the sequence is a blank – it does not exist in the bacterium’s biological language. This three-letter DNA word normally corresponds to a particular protein building block. Using a technique called mass spectrometry, Ma et al. analyzed the proteins this E. coli forms. The results showed that it has several strategies to deal with DNA transmitted horizontally into the bacterium. One method is destroying the proteins that are half-created from the DNA, using molecules called tmRNAs. These are part of a rescue system that intervenes when protein translation stalls on the blank word. The tmRNAs help to add a tag to half-formed proteins, marking them for destruction. This mechanism creates a ‘genetic firewall’ that prevents horizontal gene transfer. In organisms engineered to work from an altered genetic code, this helps to isolate them from outside interference. The findings could have applications in creating engineered bacteria that are safer for use in fields such as medicine and biofuel production.