Complete sequencing of nematode genome successfully achieved by the University of Tokyo and collaborators

A research group led by Professor Shinichi Morishita and Assistant Professor Kazuki Ichikawa (at the time of the research) from the Department of Computational Biology and Medical Sciences of the Graduate School of Frontier Sciences at the University of Tokyo, Emeritus Professor Yuichi Iino of the University of Tokyo, Associate Professor Yu Toyoshima from the Department of Biological Sciences of the Graduate School of Science at the same university, Professor Andrew Fire from Stanford University, and Dr. Erich Schwarz from Cornell University reported the complete genome sequence of the nematode (Caenorhabditis elegans) in the journal Genome Research.

For an understanding of modern biology, determining the complete genome sequence and clarifying its characteristics is crucial. The nematode was the first multicellular organism whose genome sequence was determined in 1998. Until 2005, its genome sequence was believed to be complete without gaps. However, in 2019, the research team reported that it was incomplete, leaving the complete sequencing of the nematode genome as an unresolved problem.

The initial genome sequence of the nematode was created from the standard wild strain N2. N2 is believed to have possessed genetic polymorphisms even when first cryopreserved in 1969, and genetic polymorphisms continued to accumulate into the 2000s, with no cryopreserved stock reflecting the original strain existing. Since no wild strain matching the initial genome sequence exists, the research group attempted to determine the genome sequence of strain VC2010 derived from N2 and published results in 2019, but more than 10 genomic regions could not be resolved. These unresolved regions included tandem repeat sequences of 5S rRNA genes (unit length 980 bases), 45S rRNA genes (unit length 7,197 bases), and pSX1 sequences (unit length 172 bases), and two telomere regions.

The advancement of long-read sequencing proved effective in resolving the unresolved regions. The complete human genome sequence was decoded in 2022. However, when it came to the nematode genome, the 45S rRNA gene region was a particularly difficult example to decode, and now, for the first time, the researchers are able to reveal that the total length is 772,000 bases with 107 repeats of the 7,197-base unit. They also identified 183 new genes and found that a total of 21,238 genes are encoded, including previously known genes.

As a result of having the complete genome sequence, it has become realistic to artificially design models with functionally modified genome sequences, synthesize DNA based on these modified models, ensure proliferation within cells, and experimentally verify whether the results obtained support the functional modification models. Until now, such synthetic biology has been tested in single-celled organisms such as E. coli and budding yeast. The complexity of nematodes is greater than that of single-celled organisms but smaller than that of humans, and this moderate complexity makes nematodes potentially ideal test systems for animal synthetic biology.

Journal Information
Publication: Genome Research
Title: CGC1, a new reference genome for Caenorhabditis elegans
DOI: 10.1101/gr.280274.124