By Kevin Davies

April 16, 2008 | Fifty-five years after James Watson co-authored the most famous paper in Nature magazine’s history -- the discovery of the DNA double helix with Francis Crick -- his genome sequence is also gracing the pages of the famous scientific journal.

Following months of extensive review and revision, Nature finally publishes the paper reporting the Watson’s personal genome, or “Project Jim” as it was known, this week. The sequencing itself was performed by 454 Life Sciences, part of Roche, led by its founder and past chairman, Jonathan Rothberg. The bioinformatics analysis was handled by scientists at the Baylor College of Medicine genome center, led by Director Richard Gibbs and bioinformatician David Wheeler.

Watson’s sequence becomes the second full human genome sequence to be published, following the publication of Craig Venter’s sequence last year. But whereas Venter’s genome took years of work using traditional Applied Biosystems sequencing instruments, costing a reputed $70 million, the Watson genome was sequenced in a couple of months early last year using the 454 GS FLX pyrosequencing instruments. 454 estimates the final cost to be between $1-2 million. “This is the first [human] genome sequenced by next-generation technologies,” the authors emphasize.

James Watson (left) receives a digital copy of his genome sequence from Jonathan Rothberg in May 2007.

Last May, Rothberg presented a digital copy of the raw sequence on a portable hard drive to Watson in a ceremony at Baylor College of Medicine. (Rothberg is no longer affiliated with 454/Roche.) Watson’s genome assembly – with the exception of one Alzheimer’s associated gene (APOE on chromosome 19) that was redacted at Watson’s behest -- has been publicly annotated and presented by Lincoln Stein at Cold Spring Harbor Laboratory.

The Nature paper details the highlights of Watson’s genome analysis. All told, more than 93 million DNA sequence traces, averaging about 250 bases in length, were assembled to produce the final sequence. Of those, more than 1 million did not correspond to the reference genome sequence, indicating there is much more genomic variation between individuals than previously thought. The 454 team also points out that its amplification procedure dispenses with bacteria, and thus leads to more even representation of the full genome.

The final tally of 24.5 billion bases provides more than seven-fold coverage of the genome. Wheeler and colleagues documented more than 3.3 million single nucleotide polymorphisms (SNPs), of which more than 10,000 alter the primary amino-acid sequence of proteins.

The paper contains a one-page box written by Baylor bioethicist Amy McGuire on the ethical considerations in handling and communicating this genetic and medical information with Dr. Watson.

Editor’s Note: Last year, Kevin Davies interviewed lead author David Wheeler on the sequencing of the Watson genome. See the full interview here.

Further Reading: Wheeler, D. et al. “The complete genome of an individual by massively parallel DNA sequencing.” Nature 452; April 17, 2008. doi:10.1038/nature06884