A Search for the Common Words within the Voluminous Phage Vocabulary

Abstract

4^(900) is a number that surpasses the estimated number of protons in our observable universe by roughly 462 orders of magnitude. Yet, this number corresponds to the number of sequences that can be encoded using just 900 DNA base pairs, the average gene length! Astonishingly, despite the incomprehensible sequence diversity that the DNA alphabet allows for, there exist sequences that are highly conserved across all domains of life. Such sequences have been used as "universal" markers for both identification and evolutionary classification of organisms except for phages (and viruses in general), which are the most abundant of biological entities on our planet, with an estimated 10^(31) such viruses populating the world's ecosystems. In the absence of universal phage markers, we aimed to search for the most ubiquitous phage sequences within a given microbial environment, using the human mouth as an important and intriguing case study. Upon identifying ubiquitous phage markers using a bioinformatic search through oral metagenomic databases, we designed primers to capture them experimentally. To our surprise, using DNA amplification and sequencing, we have verified the presence of these phage markers in all human patients we have sampled so far. Using these markers, we have begun to study phage sequence diversity and evolutionary relationships across different patients, various other animals and natural environments in which these markers are also present. We further aim to use these markers in microsocopy studies where we can directly visualize the networks of phages and their particular hosts in their intact microbial communities.

Additional details