Hundreds of huge, bacteria-killing viruses have been newly discovered lurking in all kinds of environments, including our guts. Their massive genomes code for many proteins not found in smaller viruses, including CRISPR systems used to attack both their bacterial hosts and rival viruses.
The massive viruses have long gone unnoticed because the standard methods used to look for bacteria-killing viruses, or bacteriophages, literally filter them out. Instead, a team has found them by looking at all the DNA present in a variety of samples, an approach known as metagenomics.
The researchers then pieced together the genomes of the huge phages using a method developed by team leader Jill Banfield at the University of California, Berkeley.
Bacteriophages are the most common entities on Earth. There can be many millions in a drop of seawater. Almost all known phages have genomes tens of thousands of DNA letters long at most. Larger ones were thought to be very rare. But earlier this year, Banfield’s team reported finding more than a dozen phages with genomes up to 540,000 DNA letters long in the guts of humans and animals.
By killing specific bacteria, these megaphages may shape the microbiome in our guts. “The potential impact on health and disease is huge,” says team member Joanne Santini of University College London.
Now the same team has analysed metagenomic data from many different environments and found hundreds more of these huge bacteriophages, including one with a genome 716,000 letters long – the largest phage genome discovered.
No one has isolated and studied the actual viruses themselves yet, so we have no idea what they look like. Nor do we have a clue what most of the extra genes these viruses have are for.
Of the genes that can be identified, some code for proteins needed to make more viruses. Normal viruses can have as few as two genes and rely almost entirely on the cells they infect to replicate themselves. But it appears the giant viruses make much of their own machinery for copying themselves.
The team thinks this self-reliance may allow megaphages to infect a much wider range of bacteria than normal phages.
Surprisingly, many of the giant phages also have CRISPR systems. CRISPR proteins have become famous for their use in genome editing, but they were first evolved by bacteria as a kind of immune system that targeted and destroyed the DNA of invading phages.
Many of the giant phages seem to have stolen parts of bacterial CRISPR systems and turned them on their hosts, using them to target specific bacterial genes. Other megaphages appear to use CRISPR to target genes of other phages, possibly to destroy any other viruses that try to infect the same cell.
The first phage with a CRISPR system was discovered in 2013, but these latest findings suggest CRISPR-armed phages are much more widespread than we thought.
It is possible that we could one day use such phages to eliminate undesirable bacteria from our gut microbiomes.
Although these giant phages are big, none has broken the record for the biggest viral genome. That crown is still held by the amoeba-infecting pandoraviruses, first discovered in 2013, which have genomes up to 2.5 million letters long.
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