Evolutionary biochemistry: revealing the historical and physical causes of protein properties

By M. Harms, Joseph W. Thornton. 2013

317 citations recorded by the source corpus.

The repertoire of proteins and nucleic acids in the living world is determined by evolution; their properties are determined by the laws of physics and chemistry. Explanations of these two kinds of causality — the purviews of evolutionary biology and biochemistry, respectively — are typically pursued in isolation, but many fundamental questions fall squarely at the interface of fields. Here we articulate the paradigm of evolutionary biochemistry, which aims to dissect the physical mechanisms and evolutionary processes by which biological molecules diversified and to reveal how their physical architecture facilitates and constrains their evolution. We show how an integration of evolution with biochemistry moves us towards a more complete understanding of why biological molecules have the properties that they do.

Subfields: Genetics, Molecular Biology

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Citations in the corpus

Coevolutionary Landscape Inference and the Context-Dependence of Mutations in Beta-Lactamase TEM-1 (2015, background): “Hence the mutation is expected to be context dependent.”
Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding (2020, unknown): “Fitness ultimately arises from the concerted action of biochemical phenotypes, which are in turn determined by genotype (Dean and Thornton, 2007; Harms and Thornton, 2013; Russell et al., 2014).”
Pervasive pairwise intragenic epistasis among sequential mutations in TEM-1 β-lactamase (2019, background): “The relative contributions of specific and nonspecific epistasis to protein evolution is an important open question [37].”
Systematic exploration of ubiquitin sequence, E1 activation efficiency, and experimental fitness in yeast (2014, background): “…deciphering how this blueprint leads to biological function is challenging due in large part to Systematic investigations of the relationships between gene or protein sequence, function and fitness provide new opportunities to bridge molecular, systems, and evolutionary biology 15; 16; 17; 18 .”
Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding (2020, unknown): “Furthermore, fitness ultimately arises from the concerted action of biochemical phenotypes, which are in turn determined by genotype (Dean and Thornton, 2007; Harms and Thornton, 2013; Russell et al., 2014).”
The effects of temperature on aerobic metabolism: towards a mechanistic understanding of the responses of ectotherms to a changing environment (2015, background): “There are very few possible structures that allow both stability at high temperatures and good catalytic activity at low temperatures, and so most mutations will tend to yield enzymes that lack these dual properties (Wintrode and Arnold, 2001; Harms and Thornton, 2013).”