When resurrected ancestors meet the physics of proteins: studying photoreceptors with a virtual time machine

Important gaps of knowledge remain in understanding how the amino acid sequence of a protein encodes its functional properties. We are approaching this question using an evolutionary strategy. Proteins found in nature often occur in protein families consisting of thousands of related proteins that were derived from a common ancestral protein. Both the function and the sequence of these proteins diverged over evolutionary time scales. This phenomenon provides a window into how sequence variation results in functional variation. Computational methods have been reported that use the information present in the variation of the amino acid sequences of proteins belonging to the same protein family to reconstruct the entire evolutionary history that gave rise to the observed sequence variation. We are using gene synthesis methods to resurrect ancient ancestral proteins that gave rise to functionally distinct proteins in present-day proteins, and are applying this approach to bacterial photoreceptor proteins. Biophysical and spectroscopic characterization of these resurrected ancestors yielded proteins with unexpected properties. We will discuss the implications of these observations for understanding aspects of the mechanistic features causing the observed functional variation.