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Biology’s ‘dark matter’ hints at fourth domain of life

Over 99 per cent of organisms remain unknown to science – so could some of them sit outside the classic three domains of cellular life?

STEP far enough back from the tree of life and it begins to look quite simple. At its heart are just three stout branches, representing the three domains of life: bacteria, archaea and eukaryotes. But a new study is hinting that this is too simple, and that we may be on the verge of discovering a fourth domain.

This bold vision is based on an analysis of water samples collected from the world’s seas. Jonathan Eisen at the University of California Davis Genome Center has identified gene sequences hidden within these samples that are radically different from any seen before.

Most species on the planet look like tiny single cells with few distinguishing features. To work out where they fit on the tree of life, biologists must be able to grow them in the lab. This allows them to obtain enough DNA for genetic analyses. The problem is, the vast majority of these species – 99 per cent of them is a reasonable bet – refuse to be cultured. “They really are the dark matter of the biological universe,” says Eisen.

To probe life’s dark matter, Eisen, Craig Venter of the J. Craig Venter Institute in Rockville, Maryland, and their colleagues have spent the last eight years collecting samples of seawater from around the world. To these, they applied a technique called metagenomics. This, says Eisen, can “sequence the crap out of any DNA samples”, whether they are collected from the environment or grown in the lab.

The analysis revealed that some sequences belonging to two superfamilies of genes – and – were unlike any seen before, ().

“The question is, what are they from?” says Eisen. Because the team has no idea what organism the genes belong to, that question remains unanswered. Eisen can see two possibilities. “They could represent an unusual virus, which is interesting enough,” he says. “More interestingly still, they could represent a totally new branch in the tree of life.”

This controversial idea has met with mixed reactions. Radhey Gupta at McMaster University in Hamilton, Ontario, Canada, calls the finding “very exciting”, but cautions that there are other possible explanations.

The sequences could be from cellular organisms living in unique habitats that caused their genes to undergo rapid evolution, which would give the false impression that they had diverged from all other cells a very long time ago and belong to a fourth domain.

Eric Bapteste at Pierre and Marie Curie University in Paris, France, is more receptive. “It’s legitimate to consider that there’s genuinely new stuff out there,” he says. “The facts are that there is lots of genetic diversity, and unquestionably most of it is unknown to us.” He adds that further analysis could determine whether the unusual gene sequences have evolved particularly rapidly or are from a cellular organism with a universally bizarre genome.

If Eisen’s gene sequences did turn out to belong to a new domain of life, it wouldn’t be the first time the tree of life has had to be redrawn. Until the 1990s, it had just two branches. And some believe that mimivirus, the largest known virus, may also represent a new domain. “If you think of those as a fourth branch, maybe our sequences represent a fifth branch,” Eisen says. “We just don’t know yet.”

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