Goldberg, D. | Search bioRxiv

bioRxiv2020

The evolution of human SIRT1 for multi-specificity is enabled by active-site adaptation

Many enzymes that catalyze protein post-translational modifications (PTM) can specifically modify multiple target proteins. However, little is known regarding the molecular basis and evolution of multi-specificity in these enzymes. Here, we used bioinformatics and experimental approaches to investigate the molecular basis and evolution of multi-specificity in the sirtuin-1 (SIRT1) deacetylase. Guided by bioinformatics analysis of SIRT1 orthologues and substrates, we identified and examined key mutations that have occurred during the evolution of human SIRT1. We found that while these mutants maintain high activity toward conserved histone substrates they exhibit a dramatic loss of activity toward acetylated p53 protein that appeared only in Metazoa. These results demonstrate that active site substitutions in SIRT1 are essential to enable the inclusion of p53 substrate. Our results are consistent with a model in which promiscuous ancestral activity can provide an evolutionary starting point from which multispecificity toward a number of cellular substrates can develop.

biochemistry↗

bioRxiv2019

Dispersal limitation and stage-specific local filtering processes vary with climate across a network of alpine grasslands

Dispersal dynamics and local filtering interactively generate regional vegetation patterns, but empirical evidence of their combined influence in nature is scarce, representing a missing link between our theoretical understanding of community assembly and real-world observation. Here, we compare seed and adult plant communities at twelve grassland sites with different climates in southern Norway to explore the degree to which community membership is shaped by dispersal limitation and local niche-based filtering, and how this varies with climate. To do this, we first divide species at each site into two groups: \"locally-transient\" species, which occur as seeds but are rare or absent as adults (i.e., they arrive but are filtered out), or \"locally-persistent\" species, which occur consistently as adults in annual vegetation surveys. We then ask questions to reveal where, when, why, and how locally-transient species are systematically disfavored during community assembly. Our results led to four main conclusions: (1) the strength of local filtering on community membership increased with temperature, (2) surprisingly, local filtering was stronger during seedling emergence than during seedling establishment, (3) climate-based niche differences drove differential performance among species, especially for seeds dispersing outside of their realized climate niches into more stressful (colder and drier) climates, and (4) locally-transient species had traits that may made them better dispersers (smaller seeds) but poorer competitors for light (shorter statures, less persistent clonal connections) than locally-persistent species, providing a potential explanation for why they arrived to new sites but failed to establish persistent adult populations. Our study is one of the first to combine seed, seedling, and adult survey data across multiple sites with different climates to provide a rigorous empirical evaluation of the combined influence of dispersal limitation and local filtering on the generation and maintenance of climate-associated vegetation patterns.

ecology↗