Computational determination of new functional RNAs from viral genomes

Benedikt Löwes (started October 2013)

Viral interactions are essential for the infection of host organisms and the subsequent replication of the viral genome in the host cell. These interactions are often based on specific RNA motifs shared between different evolutionary distant viruses. We observe that convergent evolution is a potential mechanism that explains similar motifs in phylogenetically distant viruses that infect common hosts by interacting with their cellular components. This is supported by the fact that for those specific RNA motifs similar selection criteria prevail. In this regard, the Hammerhead ribozyme is a well-studied example.

We focus on identifying new functional RNAs from viral genomes based on structural agreement of the RNA secondary structure, in order to find new examples of viral interactions with their host cells which are essential for the infection of the host and the replication of the virus. Previous approaches for identifying viral ncRNAs often strongly relied on sequence homology as well as pre-annotated RNA families in databases. Our approach, on the other hand, for the detection of the aforementioned convergent evolution uses conservation and convergence on the secondary structure level as primary information and the primary sequence only as additional source of information. This is based on the assumption that agreement on the level of secondary structure is the primary criterion for different viral RNA molecules to interact in a similar fashion with cellular components.

After identifying clusters of similar RNA elements by either only RNA structure matching, or a fast seed-based approach that takes structure and part of the sequence into account, or hierarchical RNA matching that uses an abstraction of the secondary structure, we incorporate phylogenetic information to ensure that the candidates that form a cluster with similar secondary structure stem from phylogenetically distant viruses. The most promising candidates of convergent evolution can be used as evidence to show that RNAs from phylogenetically distant viruses “look and behave” the same way, but evolved completely independent from one another by a subsequent manual analysis in the laboratory.

Supervisors: Robert Giegerich (Bielefeld University) and Peter Unrau (Simon Fraser University)

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