The Genom of Homo sapiens.pdf

The New Quantitative BiologyM.V. OLSONDepartments of Medicine and Genome Sciences, University of Washington, Seattle, Washington 98195Late on Monday afternoon, June 2, 2003, Bruce Stillmanstepped to the podium in Grace Auditorium to introducemy talk summarizing the 68th Cold Spring HarborSymposium on Quantitative Biology. In the midst of hisremarks, the power failed. It quickly became evident thatthe problem was not local—the whole laboratory and surroundingareas had gone dark. Hence, there was little todo but carry on. With only emergency runner lights alongthe outside corridors, I stared out into the dark auditorium,abandoned my PowerPoint slides, raised my unamplifiedvoice and began. The symbolism was inauspiciousfor a meeting that took a first, exhilarating look atways in which the human-genome sequence was castingnew light on biology.A sense of history enveloped the occasion. Artificial asit may have been to coordinate the announcement—or,more precisely, the latest in a series of announcements—that the human genome had been sequenced with the 50thanniversary of the Watson-Crick Nature paper, there wasa clear sense at the meeting that we were witnessing a majortransition in the history of biology. For 50 years, thefocus of molecular biology had been on understandingthe flow of information within cells, a process that ultimatelyled to the sequencing of whole genomes. Now, thegears of this vast enterprise were shifting before our eyes.At the end of his Nobel Lecture in 1955, Hugo Theorellreferred to the “yawning gulf” between biochemistry andmorphology (Theorell 1964). At the end of CSHSQBLXVIII, in the darkness of Grace Auditorium, we werelooking out at the still larger gulf between the genomeand organismal biology.The terms of encounter between biologists and livingsystems had changed. As Jim Watson said to me at themeeting:It’s like 1953. Once we had the double helix, everythinghad changed. Now we have the human-genome sequenceand everything has changed again.In her more down-to-earth style, Jane Rogers describedthe meeting as having been “a pretty good start to the humangenomic era.” Surely the main interest in these volumes,both now and in the future, will be as a record ofthat start. Perhaps it is true that “everything has changed”in biology. If so, the Symposium was a prime opportunityto see how biologists were seizing the moment.A taxonomy of the meeting’s talks is presented inTable 1. The conceptual scheme is arbitrary, and I havemade debatable judgments about where to assign particularpapers. Nonetheless, themes emerge from this roughAll authors cited here without dates refer to papers in this volume.view of the topics emphasized by the 79 speakers whopreceded me to the podium. For example, genome-analysistechnology was only lightly represented. This omissionwas all the more striking since this year’s Symposiumsubsumed the annual Cold Spring Harbor meetingon genome sequencing and biology, a traditional forumfor talks on genomic technology.GENOME SEQUENCINGAlthough there were five talks on genome sequencing,three were retrospective views of the Human GenomeProject. Each concluded that the April, 2003, release ofthe human-genome sequence was a high-quality product.Rogers (Rogers) reported that nucleotides randomly sampledfrom the 2.85 Gbp of euchromatic DNA in the April,2003, release reside on contigs of average size 27 Mbp.Fewer than 400 gaps, unspanned by analyzed clones, remain.This level of completeness resulted from thelargely unsung efforts of the expert “finishers” associatedwith ~20 genome centers. This army of finishers hand-curatedthe final sequences of 26,000 BAC clones. Schmutz(Schmutz et al.) reported that a quality-control program,based on resequencing randomly selected BACs, detectederrors at a rate