Complex Adaptations Can Drive the Evolution of the Capacitor [PSI+], Even with Realistic Rates of Yeast Sex

The [PSI+] prion may enhance evolvability by revealing previously cryptic genetic variation, but it is unclear whether such evolvability properties could be favored by natural selection. Sex inhibits the evolution of other putative evolvability mechanisms, such as mutator alleles. This paper explores whether sex also prevents natural selection from favoring modifier alleles that facilitate [PSI+] formation. Sex may permit the spread of “cheater” alleles that acquire the benefits of [PSI+] through mating without incurring the cost of producing [PSI+] at times when it is not adaptive. Using recent quantitative estimates of the frequency of sex in Saccharomyces paradoxus, we calculate that natural selection for evolvability can drive the evolution of the [PSI+] system, so long as yeast populations occasionally require complex adaptations involving synergistic epistasis between two loci. If adaptations are always simple and require substitution at only a single locus, then the [PSI+] system is not favored by natural selection. Obligate sex might inhibit the evolution of [PSI+]-like systems in other species

Developmental drift as a mechanism for aging: lessons from nematodes

Aging is a universal biological process that afflicts every creature on this planet. To date, we have a very poor understanding of what actually causes this degeneration. A commonly held view is that aging is the result of damage accumulation over a lifetime. However, research has shown that aging is not only the result of wear and tear in the organism, but also of genetic programs involved in organismal development that go awry as selective pressure is released. This review focuses on Wnt signalling pathways and discusses how these genetic programs orchestrate changes in the organism that could cause aging

Distinct Prion Domain Sequences Ensure Efficient Amyloid Propagation by Promoting Chaperone Binding or Processing <i>In Vivo</i>

<div><p>Prions are a group of proteins that can adopt a spectrum of metastable conformations <i>in vivo</i>. These alternative states change protein function and are self-replicating and transmissible, creating protein-based elements of inheritance and infectivity. Prion conformational flexibility is encoded in the amino acid composition and sequence of the protein, which dictate its ability not only to form an ordered aggregate known as amyloid but also to maintain and transmit this structure <i>in vivo</i>. But, while we can effectively predict amyloid propensity <i>in vitro</i>, the mechanism by which sequence elements promote prion propagation <i>in vivo</i> remains unclear. In yeast, propagation of the [<i>PSI</i>^<i>+</i>] prion, the amyloid form of the Sup35 protein, has been linked to an oligopeptide repeat region of the protein. Here, we demonstrate that this region is composed of separable functional elements, the repeats themselves and a repeat proximal region, which are both required for efficient prion propagation. Changes in the numbers of these elements do not alter the physical properties of Sup35 amyloid, but their presence promotes amyloid fragmentation, and therefore maintenance, by molecular chaperones. Rather than acting redundantly, our observations suggest that these sequence elements make complementary contributions to prion propagation, with the repeat proximal region promoting chaperone binding to and the repeats promoting chaperone processing of Sup35 amyloid.</p></div