Remarkably, viruses have been found in almost every known environment on earth, including the extreme acidic, thermal and saline environments of Yellowstone National Park where archaeal organisms are dominant. However, while more than 5,000 eukaryotic viruses and bacteriophage have been studied in detail, fewer than 50 archaeal viruses have been investigated at any level. Those, we are largely ignorant of viruses in this third domain of life. But why should we study these viruses? One reason is a growing appreciation of the roles viruses play in evolution. Remarkably with >500 cellular genomes sequenced to date, most show significant amounts of viral or viral-like sequence within their genomes, evidence that viruses play a central role in horizontal gene transfer, and have helped to drive the evolution of their hosts. Roles for viruses in cellular evolution are also being considered. Current hypotheses contend that viruses have catalyzed several major evolutionary transitions, including the invention of DNA and DNA replication mechanisms, the origin of the eukaryotic nucleus, and thus a role in the formation of the three domains of life. In addition, there is also considerable interest in viral genesis and evolution in and of itself. In order to evaluate these hypotheses and to analyze evolutionary relationships among viruses, knowledge of viruses infecting Archaea, the third domain of life, is clearly essential. A second reason to study archaeal viruses stems also from the exceptional molecular insight viruses have traditionally provided into host processes; thus studies of archaeal viruses are certain to provide new insights into the molecular biology of this poorly understood domain of life.

The hyperthermophilic Crenarchaeal viruses show incredible morphological diversity. This is accompanied by extreme genetic diversity, wherein most viral genes lack significant similarity to genes of known function. The lack of sequence similarity to genes of known function has, in turn, complicated efforts to elucidate viral life cycles, virus-host relationships, and the underlying genetics and biochemistry. We postulate, however, that many of the genes in these viruses are not unique. Rather, their encoded proteins bear remote similarities to proteins with known functions, but these similarities are masked by evolution and adaptation to extremes of temperature and pH. In this light, tertiary (3D) structural similarities between proteins persist longer on the evolutionary time scale than either primary (amino acid) or genomic sequence (DNA) similarities. Thus, we are pursuing structural studies of crenarchaeal viral proteins in order to arrive at testable functional hypotheses. Our work over the last three years clearly demonstrates the validity of this approach; protein tertiary structure does suggest function. And the insights gained from our structural studies are suggesting functions for an ever increasing number of viral proteins. These structure-function relationships are relevant not only to the viruses under study (SSVs and STIV), but for the Crenarchaea in general.


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Structure, Biochemistry