Prions: Agents of Evolution?

Despite significant media hype about the discoveries of genes "for" particular traits or diseases, most of us know that genetics is not destiny. This is due, in part, to the complicated influence of environmental factors. Not many scientists are arguing over nature versus nurture anymore; today, research is more likely to focus on the partnership between the two.The interaction of genes and the environment is raised to another level in the relatively new science of epigenetics. The word epigenetics literally translates to "above the genome." It refers to any changes in gene activity that do not involve changes to the genetic code (i.e., DNA) but still can be inherited from one generation to the next. Basically, epigenetics is a nongenetic form of cellular memory. For instance, all the cells in your body contain identical genetic instruction sets, yet, during development, some turn into skin cells, others heart cells, others neurons, and so on. Epigenetic factors inform each cell of its final destiny.In a special issue of Science magazine published in Oct. 2010, Randal Halfmann and Susan Lindquist present evidence for an unusual form of epigenetic inheritance involving a type of protein molecule called a prion. You may be familiar with prions as the infectious proteins that chew holes in the brains of people (and cows) with mad cow disease. However, Halfmann and Lindquist make the case that prions may also help organisms adapt to different environments and potentially drive evolution.Proteins that are able to form prions are found inside cells. They can exist in their normal shape, a nonprion conformation, but can also fold into an alternate shape, a prion conformation. Prions perpetuate themselves by bumping into other molecules of the same protein and causing them to take on the prion conformation. When the cell divides, molecules with both the prion and nonprion shapes are passed down to the daughter cells.For proteins, structure dictates function. The alternate shape a prion takes on can have profound consequences for its role inside the cell. In the cases of prions associated with neurodegenerative diseases, this is bad news. But research shows in some instances, prions can result in observable traits that are advantageous in certain environments.Prions exert their influence by interacting with other elements inside the cell, including DNA. The prion conformation can result in changes in the reading and replicating of different parts of the genetic code, or the formation of new interactions with other proteins, triggering major changes in the development of the cell or the whole organism. For instance, the prion conformation of the Sfp1 protein in baker's yeast (Saccharomyces cerevisiae) increases the cell's growth rate in nutrient-rich environments.Prions appear to function like genes in several ways. They are inheritable and can affect physiological characteristics of an organism. The broader implication of prions for evolution comes from the sensitivity of proteins and protein-folding processes to environmental conditions. Environmental stresses, like changes in temperature, pH, or concentrations of certain chemicals, can increase the rate at which prions form. Rapid switching between nonprion and prion conformations could actually help an organism adapt to a changing environment. Halfmann and Lindquist propose that the increase in prion formation in response to environmental stress is an "evolved bet-hedging strategy" in that it allows organisms to try new characteristics that may prove beneficial. Since prions are self-replicating, those resulting in successful characteristics are immediately heritable to the next generation(s).If this reminds you of Lamarck, you're not alone. His infamous example of a giraffe stretching its neck, then passing that longer neck on to its offspring, has been ridiculed since Darwin's theory of natural selection won out as the explanation for the mechanism driving evolution. Perhaps Lamarck got a bad rap. With prions, we have a convincing illustration of how a living organism can adapt to its surroundings, even at a cellular level, and pass those adaptations on to its offspring. Halfmann and Lindquist give him a shout-out, describing prions as a "quasi-Lamarckian mechanism that connects environmental conditions to the acquisition and transgenerational inheritance of new traits."Prions allow cells to switch between two heritable physiological states — one associated with the normal protein conformation and one with the prion conformation. Each form of the protein can be selected for by different environmental conditions, while the other can be maintained — yet unexpressed — for generations, ready should the appropriate environmental trigger reappear. Since the traits associated with prions are immediately inheritable, they provide a beautiful example of the reversible expression of natural genetic variation.Epigenetics has changed the way we think about the influence of genes and environment. Will prions change the way we think of evolution? The prevailing view that all variation within a species is the result of random mutations in the genetic code is clearly not the whole story. The field of evolutionary biology may have to make room for these oddly-shaped, inheritable proteins. This unusual form of epigenetics has the power to shape the flow of genetic information, affecting the fitness, and therefore, the evolution, of organisms. * This blog post is my entry in the National Evolutionary Synthesis Center's evolution-themed blog contest. Two winners will be chosen and awarded $750 for travel to ScienceOnline2012, a science communication conference to be held January 19-21, 2012, at North Carolina State University.