Sequence-Based Analysis of Eukaryotic Protein Evolution

Abstract

The goal of this thesis was to comprehend evolutionary patterns in different contexts. To get a broad spectrum of methods, three projects were included of which one is published and two are in preparation. In the first project, we looked into the fate of new mutations in protein regions that do not have a defined three-dimensional structure. Generally, the fate of a new mutation is governed by selection that can be either purifying, neutral, or positive. We could show that disordered protein regions tend to be under more positive and less purifying selection.

For the second project, we looked at four different transporter proteins that are localised in the inner plastid membrane. Plastids are organelles that are found in plants and some closely related species. The best-known type of plastids is the chloroplast, where photosynthesis takes place. The four transporter proteins shuttle phosphorylated carbon compounds across the inner membrane to allow an exchange of the products of photosynthesis and other metabolic processes to be shared between the plastids and the host cell. In our work, comparing the sequences of those transporters from various plants and algae, we could identify a new subgroup of transporters.

In the third project, we tried to understand the distribution of enzymes that regenerate the ubiquitous metabolite NAD from its breakdown product nicotinamide. There are two pathways that synthesise NAD from nicotinamide. Additionally, nicotinamide can be methylated and subsequently excreted. We found two predominant patterns in the distribution of these pathways in eukaryotes and could explain them with mathematical models and cell culture experiments.

All three projects included sequences from extraordinarily many species. The comprehensive analyses gave insight into the evolution of the respective proteins and pathways and highlight the possibilities of phylogenetic analyses.