Restricted Pleiotropy Facilitates Mutational Erosion of Major Life-History Traits

Abstract

Radical shifts to new natural and human made niches can make some functions unneeded and thus exposed to genetic degeneration. Here we ask not about highly specialized and rarely used functions but those relating to major life-history traits, rate of growth, and resistance to prolonged starvation. We found that in yeast each of the two traits was visibly impaired by at least

Live fast, die soon: cell cycle progression and lifespan in yeast cells

“…According to the Burtner group 36, the deletion of PHO85 produces a positive impact on CLS. This result is consistent with the Cln3 phenotype discussed before, but is in stark contrast with the reduced CLS observed by Marek group 33. Both groups carry out large-scale surveys using a gene deletion collection, but the procedures to assess CLS are different: Marek group 33 measured viability after nutrient starvation, while Burtner group 36 followed the outgrowth kinetics of chronologically aged cultures.…”

“…Not surprisingly, Cln3 is not the only cyclin involved in CLS regulation. Although the evidence is contradictory and far from being totally understood, the deletion of Cln2 has been shown to reduce CLS 33. The single deletions of the mitotic cyclins Clb1 and Clb2 have been shown to have the same effect 34.…”

Identifying Longevity Associated Genes by Integrating Gene Expression and Curated Annotations

“…Table 1 lists the top 10 predicted pro-longevity yeast genes. Several of these predictions are borne out by direct experimental evidence via single-gene deletions -specifically, deletion of ACS1, ETR1, UBI4, and POR1 leads to decreased lifespan (Marek & Korona, 2013). Marek and Korona (2013) did not find a significant pro-or anti-longevity effect for UBC5, HSP12, or SBA1, and they do not report results for the remainder of the top 10 genes.…”

“…Several of these predictions are borne out by direct experimental evidence via single-gene deletions -specifically, deletion of ACS1, ETR1, UBI4, and POR1 leads to decreased lifespan (Marek & Korona, 2013). Marek and Korona (2013) did not find a significant pro-or anti-longevity effect for UBC5, HSP12, or SBA1, and they do not report results for the remainder of the top 10 genes. However, UBC5 is a strong pro-longevity candidate, since it is involved in cellular stress response and mediates selective degradation of short-lived and abnormal proteins (Seufert & Jentsch, 1990).…”

“…For URA3, COX9, TOM7, MFA1, and TAR1, we do not find pre-existing corroboration of the predicted anti-longevity status in the literature. TOM7 deletion has been reported to decrease chronological lifespan (Garay et al, 2014), and it does not appear to have a strong effect on replicative lifespan (Marek & Korona, 2013). TOM7 is part of the translocase of the outer mitochondrial membrane (TOM) complex, and the mitochondrial membrane is well-known to be important in yeast longevity (Jazwinski, 2005).…”