The entire genome of the moss Physcomitrella patens was completed by scientists at the Joint Genome Institute (JGI) in Walnut Creek, Calif., a sequencing facility of the Department of Energy. The effort to derive the genetic nuts and bolts, or base pairs, of P. patens was coordinated by a consortium of international researchers from the United States, United Kingdom, Japan and Germany, and involved more than 100 scientists in the initial annotation of the genome.

Quatrano played a major role in facilitating and organizing the final assembly of the authors, annotators and writers of the manuscript. He also coordinated much of the international effort, as well as being the co-principal investigator with Brent Mishler, Ph.D. (University of California, Berkeley), on the initial request to the Community Sequencing Program of JGI.

Quatrano initiated some of the first sequences at Washington University's Genome Sequencing Center in 2002, efforts that came about from a subcontract between Washington University and Quatrano's collaborators, Professors Celia Knight, Ph.D., and Andrew Cuming, Ph.D., both of the Center for Plant Sciences, University of Leeds (UK).

The full genome project involved several additional foreign laboratories, including United Kingdom laboratories led by David Cove, Ph.D.; Cuming, a Japanese laboratory directed by Mitsuyasu Hasebe, Ph.D., and his associate Tomoaki Nishiyama, Ph.D.; and a German laboratory headed by Ralf Reski, Ph.D., and his associate Stefan Rensing, Ph.D., the first author of the paper.

The scientists at JGI who performed the overall sequencing found about 35,000 genes, represented in the full genome of just under 500 million nucleotides. Included in this genome assembly are more than 250,000 expressed sequence tags (ESTs), fragments of genes that researchers know are expressed in the moss plant.

The Washington University Genome Sequencing Center found the first 11,000 ESTs in the collaboration with the Leeds (UK) group, with the rest contributed by the Japanese and German groups, as well as by JGI, over the past three years.

"This is a pretty exciting little genome!" said Richard K. Wilson, Ph.D., professor of genetics and director of the Washington University Genome Sequencing Center. "It's really going to be a key data point for understanding the evolution of plants and the role of the genome in driving and reacting to change."

Quatrano noted that until the sequencing of Physcomitrella, the only multicellular land plants to have been sequenced were the flowering plants rice, Arabidopsis and poplar.

"It is surprising that the moss genome has so many genes," said Quatrano. "Moss is an anatomically simple plant: it doesn't have true roots, stems or leaves, nor flowers or seeds. But it has a whopping 35,000 predicted genes, many similar to what is seen in flowering plants, but about 20 percent unique to moss only."

Quatrano said that the ancestors of mosses and flowering plants diverged 450 million years ago, shortly after plants colonized land. "One can now do comparative genomics, say between a single-celled alga, a moss and a flowering vascular plant," Quatrano said.

"This enables us to look deep into the history of plants. Over the next five to 10 years, other plants that are part of a green tree of life will be sequenced, and we'll see how these genomes have evolved and what genomic changes are associated with major evolutionary transitions, such as the evolution of wood, seeds and flowers."

"The moss genome sequence is a major landmark in understanding how plants originated and evolved," said Robert E. Blankenship, Ph.D., the Lucille P. Markey Distinguished Professor in Arts & Sciences and one of the paper's co-authors. "It provides us with a wealth of information as to how photosynthetic organisms made the difficult transition from aquatic environments to land. This information may be critical in the development of new bioenergy sources."

In addition to Blankenship, the paper's other WUSTL co-author is Susan K. Dutcher, Ph.D., professor of genetics and interim chair of the genetics department in the Washington University School of Medicine.

Dutcher's interest in the moss gene comes from her desire to understand cilia, tiny organelles that project from the surface of most human cells. She hopes that the Physcomitrella genome will be used to understand human health as well as to understand plant development.

"We have been interested for the last few years in the BBS genes (Bardet Biedl Syndrome)," said Dutcher. "Children with mutations in these genes develop kidney and eye disease as well as diabetes. Comparative genomics with Physcomitrella suggests that these genes are needed in cilia in people for sensing intracellular environment. As we continue to analyze the Physcomitrella genome by comparative genomics, we are likely to be able to find other interesting genes that impact human health."

In fact, the Quatrano lab, in collaboration with the WUSTL lab of Raphael Kopan, Ph.D., in the Department of Molecular Biology and Pharmacology, recently published a paper on the function of a gene in moss called presenilin that is very similar to a gene in humans that has been implicated in Alzheimer's disease.

Quatrano's interest in the moss genome focuses on genes that give the plant drought tolerance. Once these genes are identified, it is possible that they might be genetically engineered into other plants, including food crops, to make them resistant to drought, a boon for Third World countries.

Scientists also will scrutinize the moss genome for examples of genes that are conserved — ones that appear in moss as well as other organisms, including humans — and try to discern their function.

Quatrano cited the efforts of Washington University post-doctoral researcher Pierre-François Perroud, Ph.D., who isolated the moss DNA that JGI used to sequence the entire genome, as well as helping to identify contaminating sequences that were not in the moss genome. Also, David Cove from the UK was a visiting professor at WUSTL during this time and played an important consulting role in all aspects of the project. Support for Quatrano's lab effort came from National Science Foundation grants and from Washington University.

Quatrano says the process of accumulating scientists, annotating the assembled genome and publishing the paper, while long and difficult, is well worth the effort that he and his colleagues around the globe made.

"It's a great achievement, a real watershed in plant genomics," Quatrano said.