INSIDE each one of us lies a mystery. An analysis of genes from the human gut has found DNA so unusual it could belong to microbes unlike anything that science has encountered before.
Life as we know it is split into three major groups or domains. Plants, animals and fungi are all classed as eukaryotes, whose defining feature is their nucleus. Less complex cells fall into two different divisions – bacteria and archaea (see diagram).
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But some biologists suspect new forms of life are still to be discovered – the equivalent of dark matter – not least because more than 99 per cent of microbes can’t actually be grown in the lab.
Until about 25 years ago, we had virtually no way of studying them. Since then, genomic tools have and get an idea of the range of different species.
Even with these techniques it is hard to identify completely new types of life. One problem is drawing the evolutionary dividing line between different groups of microbes. Because they can swap genes, the divisions between them become blurred, and difficult to detect. And when a DNA analysis does identify gene sequences unlike any others, researchers don’t know how to interpret them – precisely because they are so unusual.
and at the Pierre and Marie Curie University in Paris have come up with a solution. Working with at the University of Montreal, Canada, they have developed a new method for identifying particularly unusual genes.
“It’s as if they belonged to unknown lineages of microbes that diverged very early in life’s history”
They do this by focusing on 86 families of gene that, for some reason, are rarely swapped between different microbes. They reasoned that if they could find genes from these 86 families that don’t obviously belong to bacteria, archaea or eukaryotes, this might hint at gaps in our three domains of life.
In their quest, the team has turned to our guts, because the human gut microbiome is the best studied of all microbial communities, and hosts a diverse range of species.
They analysed microbiome samples, recovering about 230,000 DNA sequences that are related to known sequences in those 86 gene families. They then used these sequences as the starting point for a second analysis – a little like digging deeper into your ancestry by using your parents’ DNA rather than your own to guide the search. This revealed an additional 80,000 stretches of microbial DNA that belonged in the 86 gene families. But the sequence of bases was highly unusual in about one-third of the DNA – it shared just 60 per cent or less of its identity with any known gene sequences. That degree of difference is what you might expect to separate different domains of life, such as bacteria and archaea.
One explanation is that genes are more variable in known organisms than we thought, says Lopez. But there is an alternative. “It’s as if they belonged to unknown lineages of microbes that diverged very early in the history of life,” he says. That might mean they belong to an as-yet-unidentified fourth domain (Biology Direct, ).
Bapteste stresses that only more research will allow us to be confident that the human gut really does play host to life forms that defy classification, especially as we know nothing about the microbes that carry the strange genes. “Let’s wait to see how unusual the organisms are,” he says. In particular, it would help to know about their size and their internal structure, including the ribosomes they use to make proteins. The cell’s metabolic processes might be unusual too, says Bapteste.
But there’s no reason why we couldn’t find a new domain of life inside us. “Scientists have found a huge diversity of microbes in the human gut, so I would not expect it to be necessarily hostile to different life forms,” says Bapteste. Last year, Dusko Ehrlich at the French National Institute for Agricultural Research in Jouy-en-Josas was part of a consortium that , expanding our estimate from 3.3 million to 9.9 million. “The gut microbiome is not such a well-known playground,” he says.
But the big question remains: could it really play host to microbes from a fourth domain? “The evidence is suggestive and indeed tantalising, but would need to be confirmed,” says Ehrlich.
“I am not entirely sure what the results really mean,” says James McInerney at the University of Manchester, UK, whose research looks at the origins of the three known domains of life. He suspects that the unusual genes will turn out to belong to fairly ordinary microbes – particularly since researchers are beginning to appreciate that gene diversity might be more extreme than once thought. That would still be an exciting find, he says. “It might hint at new metabolic processes at work in our guts.”
McInerney also points out that the proposed fourth domain of life still eludes us even after 25 years of sampling DNA from the environment. But Lopez and Bapteste argue this is because recognising completely new microbes is, by definition, a challenge.
All can agree that the true significance of the new findings won’t become clear until they have actual cells containing the unusual genes – the next task on the agenda. “The good news is we now know something about them that could help us to fish them out,” says Bapteste. Like most microbes, they probably can’t be grown in the lab, but Bapteste says developments in a technology called single cell genomics should soon offer a way to sequence the genome of individual microbes, even if they can’t be cultured.
If the results reveal microbes as unconventional as their genes appear to be, biology might change – just as it did 30 years ago when researchers first realised that the archaea formed a distinct third domain of life. “The discovery of archaea revolutionised our fundamental knowledge in biology,” says Bapteste. For now, he says, we should remain cautious. “These deep lineages, if they exist, still need to be captured.”
This article appeared in print under the headline “Meet the dark matter of life”
