Frequent nonhomologous replacement of replicative helicase loaders by viruses in Vibrionaceae

Significance In recent years, numerous prokaryotic genomes have been sequenced. However, these genomes contain many genes with unknown functions, which is a fundamental obstacle to the effective use of genomic information. To solve a part of this issue, we developed a computational method named contrapositive genetics, which infers gene function from the evolutionary exclusivity with known genes. Using contrapositive genetics with protein structure prediction and in vitro assays, we identified virus-derived helicase loader genes, a key component of the DNA replication system. This study demonstrates that utilizing the evolutionary relationship between function-known and unknown genes is a promising approach to identifying genes that play important functions from function-unknown genes.