Introduction

The first genome to be completely sequenced, in 1976, was that of an RNA bacteriophage MS2, which encoded only three genes. Though the concept of comparative genomics had yet to emerge, the authors mentioned the possibility of understanding viral evolution by performing sequence searches against other viral genomes that were forthcoming. This was rapidly followed by the sequencing–by Sanger and colleagues–of the 5.4 kb-long genomic DNA of phage ФX174, and later in 1982, considerably larger sequence (>48 kb) of the genome of the molecular biology workhorse, bacteriophage lambda (λ). As pointed out by Koonin and Galperin, neither work presented the concept of sequence comparison and homology, which is now routine in any genome analysis pipeline. This may be surprising as the PIR protein sequence database was already available, and the first sequence substitution matrix constructed. However, sequence databases were not sufficiently rich in information at that time, and sophisticated and rapid methods for searching sequence databases were not common, with the Smith–Waterman algorithm a then-recent innovation, and the much faster BLAST not due to be reported for another eight years.

The first tentative comparative genomics work, as identified by Koonin and Galperin, was published by Toh, Hayashida and Miyata in 1983. This remarkable short paper identified homologues of retroviral reverse transcriptases encoded by the genome of two DNA viruses, whose life cycle was known to involve reverse transcription. In another study, Argos and co workers showed striking similarities in certain gene sequences between animal picornaviruses and plant cowpea mosaic virus, suggesting evolutionary relatedness either by independent abstraction of common host genes, or via vertical descent from a common ancestor. Finally, McGeoch and Davison worked on considerably larger genomes of the varicella zoster virus (an α-herpesvirus), and the Epstein–Barr virus (a distantly related γ-herpesvirus), and found several homologues between them.