In this week's Science, a team of US and Japanese investigators publish a study showing that protein destabilizing mutations encoding nongenetic variation can drive evolutionary innovation, shedding new light on a disputed theory. While natural selection can explain adaptation, it is unable to account for how mutations encode new function. One controversial model suggests that protein destabilizing mutations can cause structural disorder, allowing proteins to occupy multiple conformations. "Once a promiscuous protein is evolved, additional evolutionary refinement of specific function leads to specialization and restabilization," the authors say. To test this hypothesis, the researchers focused on a particular bacteriophage, looking at mutations in a host-recognition gene — called J — that confer enhanced adsorption to the virus' native receptor, as well as the ability to access a new receptor. When they looked at five strains of the virus that differed in the number of J mutations, but all encoded proteins that target both receptors, they found that some proteins were more stable than others. Further experimentation demonstrated that such instability can allow proteins to bind to their original receptors or potentially take on new functions. Together, the findings indicate that cases where a "single genotype can manifest as multiple phenotypes may be more common than previously expected and offer a general mechanism for evolutionary innovation," the researchers conclude.
And in Science Translational Medicine, a multi-institute research group presents data suggesting that certain species of bacteria in the microbiome may be responsible for lupus and potentially other chronic autoimmune diseases in genetically predisposed individuals. Previous studies have identified antibodies directed towards a self-protein called Ro60 — which plays a role in environmental stress response —in the early stages of lupus. The researchers examined oral, stool, and skin samples from 18 patients with lupus and found that they all contained bacteria with the Ro60 ortholog. Additionally, exposing T cells from study participants to Ro60 ortholog-containing bacteria triggered the secretion of proinflammatory molecules in the same way they do when exposed to human Ro60. Healthy mice colonized with Ro60-containing bacteria also experienced an immune response with symptoms similar to lupus.