Molecular co-evolution and the three-dimensionality of natural selection

Abstract

Natural selection is the force driving evolution and therefore much effort has been invested in the deciphering and understanding of the main mechanisms underlying such a force. Because of the main implications of identifying selective processes in proteins and the perspectives for defining functional/structural amino acid sites in protein structures, many models have been devised in order to search for shifts in the selective constraints throughout evolution. However, most of these models suffer from simplistic assumptions that deem results inconclusive or ambiguous. In this chapter we discuss the importance of natural selection in the emergence and generation of evolutionary novelties and the many different approaches built to identify the forces shaping the evolution of proteins. We also highlight the fact that, despite the plethora of new mathematical/statistical methods to identify selection at the molecular level, much remains to be done to build more realistic models. Molecular coevolution is among the most promising approaches to tackle the simplistic assumptions of linearity of protein sequence evolution but the field in this respect remains in its infancy. Here we discuss in depth the marriage between the linear sequence analysis of selection and the three-dimensionality of proteins through coevolutionary analyses and urge researchers to account for amino acid dependencies when looking for Darwin thoughts swamped in a sea of neutral evolution and pre-existing finite mutational and fitness landscape.