Extreme convergent evolution in defensin proteins & quantitative maps of their sequence space

Poster presented at

SMBE 2016

Gordon AMPs 2017

Defensins are small, charged, disulphide-rich eukaryotic proteins with diverse sequences, structures, and functions. Their antimicrobial activities are of particular interest for protecting crops and humans from pathogens. They have been traditionally treated as a single superfamily. However, we present evidence that there exist two ndependent evolutionary origins of defensins, based on their secondary structure element order, disulphide topology, and tertiary structures. These two superfamilies, the cis-defensins and transdefensins, exhibit some of the most extensive convergent evolution of protein sequence, structure and function. We have developed new methods of sequence alignment and analysis to overcome the difficulties of investigating such short and divergent sequences. Multivariate analysis of protein sequence space allows grouping of defensins into naturally occurring clusters which describe the residue properties that separate phyla and functions. It can be further used to design synthetic, cluster-central, archetypal defensin sequences.