Bridging the physical scales in evolutionary biology: from protein sequence space to fitness of organisms and populations

• Published in: Current opinion in structural biology 2017-02, Vol.42, p.31-40
• Main Authors: Bershtein, Shimon, Serohijos, Adrian WR, Shakhnovich, Eugene I
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biophysics - methods; Evolution, Molecular; Genetics, Population; Proteins - chemistry; Proteins - genetics; Proteins - metabolism
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2016.10.013

•Biophysical fitness landscapes (BFL) map fitness to molecular and system-level traits.•BFL of a bacterial enzyme provides accurate prediction of antibiotic resistance.•Protein quality control plays key role in shaping BFL.•BFL show how population-scale evolutionary dynamics shapes properties of proteins. Bridging the gap between the molecular properties of proteins and organismal/population fitness is essential for understanding evolutionary processes. This task requires the integration of the several physical scales of biological organization, each defined by a distinct set of mechanisms and constraints, into a single unifying model. The molecular scale is dominated by the constraints imposed by the physico-chemical properties of proteins and their substrates, which give rise to trade-offs and epistatic (non-additive) effects of mutations. At the systems scale, biological networks modulate protein expression and can either buffer or enhance the fitness effects of mutations. The population scale is influenced by the mutational input, selection regimes, and stochastic changes affecting the size and structure of populations, which eventually determine the evolutionary fate of mutations. Here, we summarize the recent advances in theory, computer simulations, and experiments that advance our understanding of the links between various physical scales in biology.