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Structure and molecular evolution
What determines amino acid substitution rates?
Evolutionary and phylogenetic analyses are the basis of understanding the the origins and properties of all living systems. Darwin noted that the manner in which any organism evolves is largely determined by its interactions with other organisms and the environments they produce, on the "tangled bank" of plants, birds, insects, and worms, all "dependent upon each other in so complex a manner." This is also true at a protein level, where the selection acting on a protein for traits such as function, structure, and stability depend on the manner in which the amino acids interact, so the substitutions that occur at one site is affected by the amino acids at other sites in the protein (as well as other proteins and biomolecules). Capturing and characterising these networks is central to developing new mechanistic models of the substitution process grounded on the underlying molecular biophysics and population biology. The simulated evolution of proteins under selection for thermodynamic stability suggests connections between substitutions and other processes described by statistical physics. By using the language of statistical physics, we can develop deeper insights into the evolutionary process. By using the tools of statistical physics, we can move us towards calculating substitution rates from first principles.