From “Low mutational load and high mutation rate variation in gut commensal bacteria”, R.S Ramiro, P. Durão, C. Bank, I. Gordo (2020), PLoS Biology 18:3 e3000617
https://doi.org/10.1371/journal.pbio.3000617
In recent years, biology has come to understand that the bacteria and microorganisms living inside animal guts are hugely influential in the functioning of the animal, affecting processes far beyond digestion. Because this microbiome and its bacterial microbiota are so important, it is important to understand how the gut microbiota functions in genetic and evolutionary terms, and how different species and strains of bacteria come to thrive or wither within the environment of the gut.
Mutation is necessary for evolution. If there is no variation, there can be no natural selection, and without new mutations, there would be a severe limit on variation. This is particularly important in bacteria, which, for a variety of reasons including their (relatively) simple biology, flexible genomes, short generation times and ability to transfer genetic material between individuals*, are able to mutate and evolve much faster than more complex forms of life. Oddly, most DNA-based microbes have more or less the same mutation rate. This suggests that their mutation rate is caused foremost by evolutionary forces, rather than the innate molecular biology of the microorganism.
Ricardo Ramiro, Paulo Durão, Claudia Bank and Isabel Gordo were investigating the microbiota of mice. They disrupted the microbiome of four mice by dosing them with the antibiotic streptomycin, and then seeded them with two strains of E. coli which had been genetically modified to fluoresce (glow) under ultraviolet light, so the new strains could be tracked over time.
Several new strains with increased mutation rates (i.e. strains which mutated more often) emerged in one of the mice, with one strain mutating a thousand times faster than normal E. coli. Looking at the genetics of these ‘mutator’ mutants, the scientists found that they all shared a mutation in the gene responsible for producing a DNA Polymerase enzyme. These protein machines speed up the process of replicating DNA (which is needed for any kind of growth) by running along a strand of DNA and building an identical strand from the four nucleotide building blocks of DNA. It appears that this mutation promotes other mutations by inhibiting the ability of DNA Polymerase to ‘proofread’ new DNA, meaning more ‘copying mistakes’ (i.e. mutations) are retained. Thus, bacteria with this alternate form of DNA Polymerase mutate much faster.
But why did this gene persist? Mutation can be advantageous, but also dangerous, particularly for bacteria which can’t shuffle their genes through sexual reproduction. If a bacteria gains a damaging (deleterious) mutation, it can’t then get rid of it – it and it’s descendants will continue to have it until they die out from being outcompeted or accumulating so many deleterious mutations that they cannot function. And deleterious mutations are significantly more common than beneficial ones. It appeared that the deleterious mutations experienced by the mutator bacteria were not sufficiently bad to wipe them out quickly, but that wasn’t the whole story. A second mutation in the DNA polymerase gene shared by all the mutators appeared to be very beneficial, and strongly improved the bacteria’s ability to grow. The researchers speculate that the advantages of this second mutation allowed the first mutation to be carried along and the mutator bacteria to grow common, even though the mutator mutation itself was not beneficial. However, neither of these mutations reached ‘fixation’ – the point where an entire population is carrying a gene – suggesting that however helpful the mutations were, there are many other processes influencing which bacteria were able to thrive in the mouse gut.
Evolution is incredibly complicated. Theoretically, experimental evolution experiments like this one allow us to control certain factors, making it less complex and easier to understand. But this experiment shows that even when you can have some level of control, there are still a lot of processes going on which can have all sorts of unexpected impacts. We’re still a fair way from a complete understanding of evolution.
*Horizontal gene transmission, Leicester University have a decent summary of the principal mechanisms here: https://www2.le.ac.uk/projects/vgec/schoolsandcolleges/Microbial%20Sciences/mutation-and-gene-tranfer
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