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A standard genome for heavily studied worms is restarted


A new study led by Cornell finds that the genome for a widely researched worm, on which countless studies are based, is flawed. A fresh genome sequence will now set the record straight away and improve the accuracy of future research.

C. elegans

Marie-Anne Félix / Ecole Normale Supérieure

The nematode worms Caenorhabditis elegans. The three stages of C. elegans are shown: adult hermaphrodite, smaller larvae, and eleven new eggs (with embryos developing inside them). These are all on a lawn of Escherichia coli bacteria (eaten by the worms as food). The adult adult is approximately 1 millimeter long.

When scientists study the genetics of an organism, they start with a standard genome that is sequenced from one strain that acts as a baseline. It's like a chess board in a chess game: each table is the same basic.

One example organism that scientists use in research is worms of the name Caenorhabditis elegans. The worm – the first multicellular eukaryone (animal, plant or fungus) to have its genome sequenced – is easy to grow and has a simple biology without bone, heart system or circulatory system t . At the same time, we share many genes and molecular pathways with people, making it a real model for studying the role of genes, drug treatments, aging and human diseases such as cancer and diabetes.

Genetic studies of C. elegans were based on one strain, from the name N2, which researchers have ordered for decades from C. elegans stock center at the University of Minnesota. Although people tried to maintain a common standard, individual N2 stress laboratories grew on their own, which led to transformation.

“Over the past decade, with more advanced genetic experiments using high levels of DNA sequencing, scientists were afraid to discover that there is no longer a laboratory stress that everyone was using,” said Erich Schwarz, assistant research professor in the Department of Molecular Biology and Genetics. . “Over 40 years have raised many different types of N2; we cannot rely on any of them to do experiments. ”

Schwarz is a new senior study author published in May 23 in Genome Research describing one genetic clean strain, from the name VC2010, where each individual is identical. Schwarz and colleagues from the University of Tokyo, Stanford University, the University of British Columbia and the University of Minnesota used innovative techniques to sequence VC2010 genome and create a new standard.

“Before 2015, we could not have done the project we announced now,” Schwarz said. “The technology wasn't there.”

Earlier iterations of genome sequencing technology could read up to 150 nucleotide letters (the basic structural unit of DNA) at a time, and then stitch them together to produce the full genome. The current technology provides a more complete “long-lasting sequencing” that can immediately read thousands of basic pairs, even up to one million, of one single DNA molecule.

As part of the study, researchers compared VC2010 with the original N2 genome. They expected a game almost perfect, but surprising. “Along with the 100 million nucleotides we expected to see, we discovered 2 million extra nucleides, two extra percent of the genome,” which was hidden in the original, according to probably due to the limitations of the old technology, Schwarz said.

In the past, people studying C. gengans genetics could not analyze the hidden sequences. “Literally, you add two percent,” Schwarz said. “If the mutation is [you seek] happens to be within the hidden two hidden, now you have a chance to see them. ”

Schwarz added that similar issues are likely to occur in the standard genomes of other organisms, including humans. “It shows us that having the true whole DNA of an animal is not as easy as we thought it was,” he said.

Other laboratories have started to use modern sequencing equipment to reassess other genomes, which have implications for synthetic biology, where scientists create life – such as bacteria – from the beginning. “Having a really good DNA sequence is an important baseline,” Schwarz said.

Leading authors include Jun Yoshimura and Kazuki Ichikawa in the laboratory of co-author Shinichi Morishita, professor of computational biology at Tokyo University, and Massa Shoura and Karen Artiles in laboratory & co-author Andrew Fire, pathology teacher and genetics at Stanford University.

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