Scientists have sequenced the complete genome of a roundworm used extensively in biological research, opening a new pathway for synthetic biologists to build and test genetic changes in a multicellular animal species. The fundamental breakthrough will benefit research on human diseases, including cancer.
In a paper published July 15 on the cover of Genome Research, scientists at Cornell, the University of Tokyo, Stanford University, the University of Minnesota and Rockefeller University described their decade-long effort to fully identify the genome of Caenorhabditis elegans (C. elegans), a transparent roundworm nematode about 1 millimeter in length that researchers around the world have used for over 60 years to elucidate fundamental understanding of genetics and cell communication and development.
Certain organisms - such as fruit flies, brewer's yeast and E. coli - are used widely among the research community as model species to explore basic biology. This uniformity allows scientists to test, replicate and build upon each other's work more consistently. C. elegans became a model species in the 1960s and was used to conduct Nobel Prize-winning research on "genetic regulation of organ development and programmed cell death."
With a model species like C. elegans, it's critically important that scientists work from genetically identical material so that genetic abnormalities of the organisms in various labs don't disrupt findings, said Erich Schwarz, paper co-author and assistant research professor of molecular biology and genetics in the College of Agriculture and Life Sciences.
"If you're trying to understand human medicine, human biology, you can start by studying much simpler organisms. Because we have a common evolutionary ancestor, many of the basic genetic processes that we care about in humans also occur in organisms like E. coli and C. elegans," Schwarz said. "In a model animal that you want to manipulate, knowing the 'normal version' of their genetic code is a very important thing."
With the rapid development of genome sequencing in the 1990s, scientists began mapping the genomes of model species. Researchers identified single-celled E. coli's genome in 1997 and described what they believed to be the full genetic code of multicellular C. elegans between 1998 and 2005. However, it became clear by 2019 that C. elegans' genome description was incomplete. In addition, over 60 years of widespread use, genetic variations had begun to crop up in the organisms used in labs - an observation made by Andrew Fire, paper co-author, Stanford professor and 2006 Nobel Prize winner, Schwarz said.
With continued advancements in genome sequencing technology and painstaking efforts, the 14 researchers at five universities have now corrected the full genome. They discovered 183 genes that had never been identified before and 6 million more base pairs in the organism's genome than had previously been known. First author of the paper is Kazuki Ichikawa, assistant professor at the University of Tokyo.
Basic science like this is harder for the public to understand but is crucial to lay the groundwork for advancements in medical research and other fields, Schwarz said. For example, scientists in the 1980s made breakthroughs in understanding oncogenes - genes strongly associated with cancer development - by conducting research with C. elegans and fruit flies, he said.
Now, synthetic biologists are working toward future breakthroughs by manipulating and even fully constructing genetic codes in plants and animals. Initial efforts have been made in single-celled organisms, like the bacteria E. coli or the fungus S. cerevisiae, more commonly known as brewer's yeast. C. elegans, as a multicellular animal, would be "the next step up," Schwarz said.
"Having this complete, corrected genome for C. elegans is a very basic resource that will allow other people to drive down an intellectual road and discover things we can't even imagine yet," he said.
The research was supported by the Japan Agency for Medical Research and Development, the Beckman Foundation, the American Heart Association, the U.S. National Institutes of Health and Cornell University.
Krisy Gashler is a writer for the College of Agriculture and Life Sciences.
