Groups - Geneva - Computational Evolutionary Genomics

Summary

The Computational Evolutionary Genomics Group (CEGG) carries out research in the field of comparative genomics and molecular evolution, focusing on multiple genome analysis to elucidate and quantify evolutionary processes that shape the repertoires of protein-coding genes, non-protein coding RNAs (e.g. microRNAs) and Conserved Non-Coding sequences (CNC). The research studies the function of such elements on the basis of sequence variability among different species and within populations, and addresses questions concerning the robustness and evolvability of molecular systems.

Introduction

Comparative genomics strives to understand “Nature’s experimentation”, which results in genomic sequence variability. It does this by analysing the rapidly accumulating amounts of sequencing data in order to assess the selection pressure on functional elements as well as to generate and to statistically test more fundamental hypotheses of the origin and evolution of biological complexity. In this way, we employ multiple genome analysis to elucidate and quantify evolutionary processes that shape the repertoires of proteins, ncRNAs and CNCs as well as to investigate their functions. With a particular focus on medical and evolutionary questions, the group collaborates extensively with experimental functional genomics laboratories and participates in international consortia, such as the VectorBase project, which is establishing a gateway for genomic research on invertebrate vectors of human pathogens.

Projects and Services

Evolution of protein-coding and ncRNA gene repertoires

Orthology is the key concept in comparative genomics. It defines the ancestral relationships between genes of different species and enables the tracing of their evolution, and speculation about their function, by extrapolating our knowledge from model organisms. This issue is particularly challenging at the scale of multiple animal genomes and, in collaboration with the Swiss-Prot group, computational procedures are being developed for the robust identification of orthologous gene relations. The evolution of larger orthologous genomic regions (synteny) is also being studied to understand the dynamics of genome architectures and gene co-regulation.

Elucidating the functions of Conserved Non-Coding sequences (CNCs)

Animal genomes arguably harbour repertoires of conserved-through-selection non-protein coding sequences as large as the repertoires of protein coding genes. Our knowledge of these functional elements encoding ncRNA genes and a heterogeneous class of CNCs remains relatively limited. Nevertheless, comparative genomics offers new ways to approach the problem of their identification and characterisation at the genomic scale. Although some ncRNA are known to contribute to major cellular processes, and some CNCs have been shown to act as enhancers of gene expression, the complete picture remains to be determined.

Robustness and evolvability of molecular systems

The question of the origin and evolution of biological complexity is intriguing. A protein complex or pathway has additional systemic properties that can acquire specific functions that the components individually could not perform. However, how these system-level functions emerge and are selected through evolution is not clear. What defines the robustness of a molecular system that balances between the pressure to perform original functions and the ability to accommodate changes? Knowledge of protein complexes and pathways is growing rapidly making it possible to trace the evolution of whole systems and of each of their components using comparative genomics. The ultimate goal is to generate quantitative models of such molecular systems that would have further predictive value.

The CEGG is setting up: