Phylogeny and Sequence Space: A Combined Approach to Analyze the Evolutionary Trajectories of Homologous Proteins. The Case Study of Aminodeoxychorismate Synthase.

Sylvain Lespinats,Eric Maréchal,Delphine Grando,Dominique Van Der Straeten,Benoît Colange,Olivier Bastien,Vera Gorelova,Olivier De Clerck,Fabrice Rébeillé

doi:10.1007/s10441-019-09352-0

Abstract

During the course of evolution, variations of a protein sequence is an ongoing phenomenon however limited by the need to maintain its structural and functional integrity. Deciphering the evolutionary path of a protein is thus of fundamental interest. With the development of new methods to visualize high dimension spaces and the improvement of phylogenetic analysis tools, it is possible to study the evolutionary trajectories of proteins in the sequence space. Using the data-driven high-dimensional scaling method, we show that it is possible to predict and represent potential evolutionary trajectories by representing phylogenetic trees into a 3D projection of the sequence space. With the case of the aminodeoxychorismate synthase, an enzyme involved in folate synthesis, we show that this representation raises interesting questions about the complexity of the evolution of a given biological function, in particular concerning its capacity to explore the sequence space.

Highlights

The determination of the main parameters that can explain the evolutionary dynamics of a protein in a mathematical abstract sequence space remains a major difficulty in the study of molecular evolution (Starr and Thornton 2016)
We proposed a new way to explore these fundamental questions by mapping phylogenetic trees onto a representation of the protein sequence space, and we applied this approach to explore the evolution of two enzymes, the dihydrofolate reductase (DHFR) and the dihydropteroate synthase (DHPS) involved in the biosynthesis of folates (Gorelova et al, 2019)
We demonstrate that it is possible to investigate the evolutionary trajectories in the sequence space by representing phylogenetic trees onto a projected sequence space

Summary

INTRODUCTION

The determination of the main parameters that can explain the evolutionary dynamics (velocity and trajectory) of a protein in a mathematical abstract sequence space remains a major difficulty in the study of molecular evolution (Starr and Thornton 2016). By contrast, based on a computational approach, Povolotskaya and Kondrashov (2010) showed that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe and that 3,53.1009 years have not been enough to reach the limit of this divergent evolution These different conclusions could be explained by the fact that Povolotskaya and Kondrashov (2010) focused on the number of possible functional sequences of a given length, and on the rate of divergence of distant protein sequences. An example of application is provided with the case of the aminodeoxychorismate synthase (ADCS), another enzyme involved in folate synthesis (Gorelova et al 2019; Rébeillé et al 2006)

Identification of putative orthologs and protein analysis

Meaning of axes

Phylogeny of chorismate binding region

Conclusion