Minimal Life: Nature’s smallest life

This week at the National Science Foundation headquarters in Arlingon, Virginia, a small group of researchers got together for a workshop about “minimality” in biology. Participants considered the teeniest living cells, the shortest genomes, the simplest engineered systems — basically asking, how low can you go and still have “life”?

The morning sessions on 10 August focused on “unusual life”. Stephen Giovannoni of Oregon State University in Corvallis talked about SAR11, a clade of tiny planktonic bacteria that happen to be the most numerous microorganism in the ocean’s uppermost waters. Evolution has done an impressive job trimming the fat from SAR11’s genomes — the genome of one member, Pelagibacter ubique, has no introns, extrachromosomal elements, transposons or non-coding genes, and has the shortest between-gene “spacers” known. With only 1.3 million base pairs, its genome is the smallest of any free-living microorganism — although a similar claim was made by almost all the speakers today about their organisms — and makes up 30% of their teeny cell bodies.

Such a barren genetic code means SAR11 is pretty dependent on its environment. It may not be a traditional parasite, in that it isn’t constantly sucking the life force of another organism, but it does make you wonder where to draw the line between an organism and its environment. SAR11 depends on seawater for five essential cofactors, as well as for the amino acids glycine and serine. And as reported last year in Nature, it must get reduced sulfur compounds that are made by other plankton.


Howard Ochman of the University of Arizona talked about the evolutionary processes that might lead to small cells and genomes. He postulated that bacteria have a “pervasive mutational bias toward deletion”. In contrast, when a mutation deactivates a gene in eukaryotes, the “pseudogene” remains, accumulating and filling the genome with noncoding DNA.The bacteria’s progression toward a compact genome doesn’t appear to have a purpose. “It doesn’t matter how many genes there are to the overall replication rate,” he says.

Many think about evolution as leading from simple organisms to complex, but bacteria don’t seem to have taken this path. When ancestral, free-living bacteria with chunky genomes moved into nutrient-rich hosts (like humans), many of the bacteria’s genes became superfluous and become inactivated. Through an unknown mechanism, according to Ochman, the bacterial bias for deletion removes these “dead genes”. Such bacteria, with tightly-packed coding regions, can have genomes nine times smaller than Giovannoni’s Pelagibacter. It brings up an interesting difference between bacteria and eukaryotes: In bacteria, genome size is tightly linked to gene number, but while mice and humans have about the same number of genes, the mouse genome is about 15 percent smaller than ours.

The audience (which, by the way, was composed entirely of men, except for the meeting coordinator, an NSF representative, and your Nature reporter) got excited when Krastan Blagoev, the NSF program coordinator, suggested talking about the ethics of “engineering life”, which was the subject of the afternoon sessions. Tom Knight led the discussion, and wanted to talk about how to present the work to the public. “For a lot of people,” he said, “it sounds like we’re taking over the reins of creation. We can talk all we want about how safe it is, what we plan to do it, how to assure that the things we do are constructive and not destructive, but there will still be a hwole set of people out there who will look at it from the perspective of, are we playing God?”

To which Andy Ellington of University of Texas in Austin replied: “Why don’t we just ignore it?”

“We have to be honest with what we’re doing, and speak as scientists,” Ellington said. “NSF is walking into a minefield by talking about minimal life. By stating that we’re creating, defining, minimizing life, we’re by necessity saying that we know what life is, and immediately taking on the religious connotation of life. It’s a hugely loaded term, and brings up Frankenstinian stuff about mucking with life.”

“I’d prefer the term be eliminated from biology books,” he said, favoring a more specific term.

Eric Smith of the Santa Fe Institute in New Mexico argued that “we shorten the discussion of things we don’t understand by substituting inadequate smaller ideas” — such as minimal ‘cells’, as the cell theory of life isn’t always adequate.

“I’d hate to lose the term life when we don’t know what it means,” Smith said.

Clyde Hutchison of the J Craig Venter Institute in San Diego, California, said that they are, in fact, interested in the question of what ‘life’ is. “So are religions. Different approaches lead to different conflicts. Religions wouldn’t like the idea of no difference between life and not life.”

Ellington responded, “by saying we’re both interested in learning about life, we’re saying that there’s something special about life. That’s a profound limitation. This is like the virus/non-virus debate that was ultimately useless.”

Harold Morowitz of George Mason University, the lead organizer of the event and a venerable big gun in the field of minimal life, quieted things down when he said “there was nothing implied” in using the l-word in the title of the workshop. “It’s a way of asking questions about biotic systems, organisms and ecosystems, and how they function. That gives us plenty to talk about.” With which he dismissed the group to lunch.

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Minimal Life: Nature’s smallest life

This week at the National Science Foundation headquarters in Arlingon, Virginia, a small group of researchers got together for a workshop about “minimality” in biology. Participants considered the teeniest living cells, the shortest genomes, the simplest engineered systems — basically asking, how low can you go and still have “life”?

The morning sessions on 10 August focused on “unusual life”. Stephen Giovannoni of Oregon State University in Corvallis talked about SAR11, a clade of tiny planktonic bacteria that happen to be the most numerous microorganism in the ocean’s uppermost waters. Evolution has done an impressive job trimming the fat from SAR11’s genomes — the genome of one member, Pelagibacter ubique, has no introns, extrachromosomal elements, transposons or non-coding genes, and has the shortest between-gene “spacers” known. With only 1.3 million base pairs, its genome is the smallest of any free-living microorganism — although a similar claim was made by almost all the speakers today about their organisms — and makes up 30% of their teeny cell bodies.

Such a barren genetic code means SAR11 is pretty dependent on its environment. It may not be a traditional parasite, in that it isn’t constantly sucking the life force of another organism, but it does make you wonder where to draw the line between an organism and its environment. SAR11 depends on seawater for five essential cofactors, as well as for the amino acids glycine and serine. And as reported last year in Nature, it must get reduced sulfur compounds that are made by other plankton.

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