A structural perspective of compensatory evolution

Abstract

The study of molecular evolution is important because it reveals how protein functions emerge and evolve. Recently, several types of studies indicated that substitutions in molecular evolution occur in a compensatory manner, whereby the occurrence of a substitution depends on the amino acid residues at other sites. However, a molecular or structural basis behind the compensation often remains obscure. Here, we review studies on the interface of structural biology and molecular evolution that revealed novel aspects of compensatory evolution. In many cases structural studies benefit from evolutionary data while structural data often add a functional dimension to the study of molecular evolution.

Figure 1

Thermostability compensation in mammalian mitochondrial tRNAs. (a) The secondary structure of the human mt-tRNA^Trp with the known pathogenic mutations from Mitomap [68] shown in red. All instances when the disease mutation is found to be compensated in another species, as judged by a secondary structure-based alignment [69] are shown in orange. (b) An example of two direct WC compensations in the secondary structure of the Philippine tarsier mt-tRNA^Trp. (c) An example of an allosteric compensation in the anticodon stem of the sei whale mt-tRNA^Trp.