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Biomedicine

The Ocean's Unforeseen Genomic Bounty

Craig Venter sails his yacht around the world and returns with the genetic code for 6 million never-before-seen proteins.

The ocean hosts a stunningly–and surprisingly–diverse menagerie of microorganisms, according to a massive genetic study published today. The findings come from genomics pioneer Craig Venter’s expedition to circle the world by yacht, collecting and analyzing marine organisms along the way. The unexpected level of diversity suggests that despite the nearly 200 organisms that have been sequenced to date, researchers have just begun to scratch the surface of the earth’s genetic repertoire.

Sequencing the sea: Genomics pioneer Craig Venter circled the globe in his yacht, collecting ocean samples for genomic analysis along the way.

“We have not understood much about our own planet and our own environment,” Venter told Technology Review from his boat, the Sorcerer II, currently in the Sea of Cortez, in Mexico. “We’ve been missing as much as 99 percent of the life forms and biology out there.” He says the genetic sequences generated by the project will have a broad impact, from helping scientists understand global carbon cycles to identifying possible life on Mars.

Microorganisms make up the bulk of life on Earth, playing a major role in carbon cycling and other global energy cycles. Yet because only about 1 percent of the organisms can be grown in a lab, identifying and understanding these microscopic creatures is difficult. Now, ever-improving gene-sequencing methods developed over the past few years offer microbiologists a new tool with which to study the other 99 percent. Scientists can extract the genetic material from a drop of seawater and then sequence that DNA, deriving genomic clues into all the organisms living in that environment.

After a successful pilot study of the Sargasso Sea in 2003, Venter embarked on a much longer expedition, following the route of the British ship the Challenger, a research voyage that catalogued 5,000 new marine species in the late 1800s. The crew traveled nearly 6,000 miles aboard Venter’s yacht, collecting samples of surface water every 200 miles.

The first set of results, published this week in three papers in the journal PLoS Biology, revealed six million new proteins, doubling the number of known protein sequences. “Everywhere we sampled, we found new proteins,” says Venter.

Researchers focused largely on analyzing new protein-coding sequences, rather than on identifying specific microorganisms, because the variety of DNA made it difficult to assemble into single genomes. (DNA sequences generated from a drop of seawater contain fragments from the genomes of many different microorganisms. Scientists liken this to trying to put together a puzzle from a box containing a few pieces from a thousand different puzzles.)

This new collection of proteins should shed light on how proteins evolved, and perhaps even hint at the genetics of our earliest ancestral organisms. “With a diverse collection of proteins, you can build a phylogenetic tree and try to infer function and how it evolved,” says Shibu Yooseph, a scientist at the J. Craig Venter Institute, in Rockville, MD, and the lead author of one of the PLoS Biology papers. “For every family we’ve looked at, both the number and diversity of new proteins was really unexpected.”

One of the most abundant types of protein identified in the study comes from proteorhodopsins, molecules that resemble light-sensing proteins in the human eye. They appear to endow microorganisms with an alternative mechanism to photosynthesis in order to generate energy from light. Researchers also found that slight changes in the protein affect the wavelength of light the organism can absorb: the particular variant an organism possesses seems to follow the predominant color of water in its environment. On the coast, for example, where the water is green, organisms can mostly absorb green light. But in the deep sea, where the water is blue, organisms can mostly absorb blue light.

In fact, every environment sampled showed high genetic diversity, both within and between samples. The findings are challenging the notion of species in microorganisms. “When you look at microbes, they don’t appear to be individual species,” says Douglas Rusch, also a scientist at the Venter Institute and an author of one of the papers. “It seems to be a complex mixture, which we describe as subtypes, which are adapted to a particular environment.”

Venter’s project is part of a new trend in genomics, enabled by new sequencing technologies, to sequence entire microbial communities rather than individual organisms. “These technologies allow massively parallel sequencing, so we can get hundreds of thousands of sequences in single runs,” says George Weinstock, codirector of the Human Genome Sequencing Center at Baylor College of Medicine, in Houston. So far, scientists have sequenced the microbial inhabitants of whale carcasses, sewage-treatment plants, acid-mine drainage sites, and termite intestines, among others.

“Microbial communities are almost like a superorganism, where each microbe is contributing to community as a whole,” says Weinstock. “We really need to characterize the metagenome and analyze the genes and protein products as an aggregate.”

Venter and others eventually hope to find proteins that can be co-opted to create novel bacterial machines–proteins involved in hydrogen production or carbon fixation, for example, that could one day be engineered to boost the carbon-fixing capacity of the ocean or to create fuel-producing bacteria. “Genes are the design component of the future,” says Venter.

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