A new paper in Nature details how prions might generate heritable phenotypic diversity. In general, the heritable variation that underlies evolution is thought to find its root in mutations affecting the genetic code. In recent years, however, other potential mechanisms have been investigated, collectively known as epigenetics. This means that, even without changing the genetic code itself, heritable variation might be generated. The two most well-known mechanisms that achieve this are DNA methylation and chromatin remodeling.
Now, it is proposed that prions might act as epigenetic elements of inheritance. Prions are misfolded proteins which are thought to be quite detrimental and are implicated in several neurodegenerative diseases. But the new study shows that they shouldn’t be considered all bad (in yeast at least).
The researchers investigated about 700 wild yeast strains, and found prions in many of these. The prion under consideration finds its origin in the protein Sup35, which normally acts as a translation-termination factor. Basically, it tells the cellular machinery where to stop reading the genetic template in order to construct a certain protein. But, in stressful conditions, this Sup35 protein can switch into a prion, known as [PSI+]. When this happens, the ‘stop-signals’ are no longer recognized, leading to a reading of the entire strand of mRNA (the template mentioned earlier), thereby allowing cryptic variation to be expressed. This, in turn, can result in a great variation in traits. In the words of the authors:
Regions downstream of stop codons frequently accumulate genetic variation. [PSI+]-mediated read-through allows this previously cryptic variation to have biological consequences at multiple loci simultaneously. The complex traits produced by this prion would be less likely to evolve if the individually contributing mutations had to be selected for as they arose.
And what’s more, these prions can be inherited by daughter cells. A molecular machine, with the name of Hsp104, severs prion fibers, which allows prion templates to be faithfully inherited.
As time passes, it might even become possible for this prion-generated variation to be assimilated, which means that the trait might persist, even after the prion is gone. As the article says:
In the long run, reduced translational fidelity should be detrimental. However, advantageous phenotypes initially dependent on [PSI+] might be assimilated by various means, allowing the prion to be lost and the trait maintained.
Overall, the conclusion reads:
Most of the 25 prions discovered to date are RNA-binding proteins, DNA-binding proteins and signal transducers — proteins that play key roles in governing the flow of information in cellular networks. Prion-mediated alterations in such functions allow access to complex traits in a single step. Together, the interface between prions, environmental stress, cryptic genetic variation and fixation provide a means to transition from a Lamarckian mode of inheritance to a Darwinian framework of mutation and natural selection. …prions provide a robust route to the inheritance of environmentally induced traits that has moved from being merely plausible to demonstrable.
For some background about the research, and the challenges faced by lab-leader Susan Lindquist, see this News Feature by Nature.
Reference
Halfmann, R.; Jarosz, D.F.; Jones, S.K.; Chang, A.; Lancaster, A.K. and Lindquist, S. (2012). Prions are a common mechanism for phenotypic inheritance in wild yeasts. Nature. Doi:10.1038/nature10875.
