Background and state of the art
Virus evolution is subject to several restrictions, which include the rather small size of the viral genome and the necessity to replicate in a host cell, i.e. to try go undetected by the immune system of the host. On the other hand, many viruses evolve very fast, as their replicases lack a proof-reading system. Thus, viruses can adapt themselves quickly to changing environmental conditions, such as treatment with antiviral drugs. Understanding virus evolution is not only of academic interest, but is necessary to predict drug-resistance mutations or the epidemic potential of certain viruses. Analysis of virus evolution is complicated by the frequent occurrence of overlapping reading frames. This phenomenon is observed in small sized retroviruses such as HIV, but also in large RNA virus genomes such as those of coronaviruses, disproving the current belief that this phenomenon is basically limited to small viral genomes. In fact, it is thought that the SARS coronavirus only became easily transmittable from human to human after a rearrangement of overlapping reading frames among the accessory genes which occurred during adaption of this bat virus to the human host. The evolution of overlapping reading frames has not been analyzed in a systematic way so far.

The project
A systematic analysis of overlapping viral reading frames will be carried out in coronaviruses The analysis will involve codon usage analysis, prediction of the secondary structure of RNA at the frameshift sites, studies of the mutations of the overlapping genes, predicting disorder content of the “overlapping proteins”  and will be complemented by structural studies of the "overlapping proteins" .One of the questions to be answered will be whether the evolution of both genes constitutes a compromise, or whether one of them is being optimized while the other has to compromise.

People in this Project

Aditi Shukla, MSc. BioinformaticsDoctoral Candidate
Thomas Martinetz, Prof. Dr. rer. nat.Investigator
Rolf Hilgenfeld, Prof. Dr. Dr. h.c.Investigator

Publications

Shukla A, Hilgenfeld R. “Acquisition of new protein domains by coronaviruses: Analysis of overlapping reading frames coding for proteins N and 9b in SARS coronavirus” Virus Genes, doi: 10.1007/s11262-014-1139-8, November 2014

Liu DX, Fung TS, Chong KK,  Shukla A, Hilgenfeld R. “Accessory proteins of SARS-CoV and other coronaviruses” Antiviral Research, doi:10.1016/j.antiviral.2014.06.013., July 2014