Box 1. Box 1 What makes a completely sequenced genome?

When is sequencing work on a genome complete? No genome for a eukaryotic organism — roughly, those organisms whose cells contain a nucleus — has been sequenced to 100%. There are regions, often highly repetitive, that are difficult or impossible to clone (one of the initial steps in a sequencing project) or sequence with current technology. Fortunately, such regions are expected to contain relatively few protein-coding genes^{4, 10}.

The extent of these regions varies widely in different species. So, rather than applying a universal gold standard, each sequencing project has made pragmatic decisions as to what constitutes a sufficient level of coverage for a particular genome. For example, as much as one-third of the sequence of the fruitfly Drosophila melanogaster was not stable in the cloning systems used, and so was not sequenced. But 97% of the so-called euchromatic portion — where most genes are thought to reside — was sequenced ¹¹ (Fig. 1).

For the human genome, one definition of 'finished' is that fewer than one base in 10,000 is incorrectly assigned⁶; more than 95% of the euchromatic regions are sequenced; and each gap is smaller than 150 kilobases ¹². Such standards represent realistic goals given current technology. By this standard, over a quarter of the public consortium's sequence¹ is considered finished at present, including the previously published long arms of chromosomes 21 and 22 (refs 3, 4; Fig. 1). The Celera sequences of chromosomes 21 and 22 are slightly more gappy than those from the public consortium, but the converse seems to be true for the other chromosomes². But again, as different protocols were used, it is not easy to compare the overall status of the two assemblies. In the longer term, as much of the heterochromatin — which is harder to sequence, and contains few genes — as possible must be sequenced, because we might otherwise miss important features. P.B. & R.C.