The top line result of the sequencing of the human genome - the mappers' conclusion that there are only about 30,000 human genes - may do little to change the competitive landscape in biotech. After all, companies have been discovering and filing patents on genes and proteins for the last 20 years. But the details of both what has been found so far and, equally important, what is not yet known, point to fields of opportunity for companies in terms of drug discovery and intellectual property.

Thus the work published last week in Science and Nature by groups led by Celera Genomics Group and the International Human Genome Sequencing Consortium (IHGSC), respectively, point to several areas of commercial opportunity.

Specifically, because it appears that there may be only 30,000 or so genes, cellular operations downstream from the genome take on increased importance to account for the multitudes of proteins and their behavior (see How They Did It", A11, & "The Opportunity", A2). As the CRA paper noted: "The modest number of human genes means that we must look elsewhere for the mechanisms that generate the complexities inherent in human development."

Put another way, Donald Corcoran, president and CEO of MethylGene Inc. (Montreal, Quebec), noted that a genome with fewer genes but more proteins simplifies the upstream picture of how the body works. But it complicates the downstream picture and justifies giving more attention to those downstream events:

• Protein diversity will spur inquiry into alternative splicing of genes to produce different protein isoforms, post-translational modification of proteins, and protein-protein interactions.

• Non-coding DNA may provide new regulatory targets, rather than being the "junk DNA" that was once thought.

• Methylation, one of the ways that cells regulate long-term gene expression, may find greater interest as a regulator of phenotypic variability.

• RNA, as an integral player in the translation of a gene into a protein, also will become more important as a target.

Meanwhile, the identification of millions of SNPs by both groups will provide an opportunity to more effectively relate them to diseases directly, while the search for new genes themselves will still have a place as biological experiments test the accuracy of the mappers' algorithms and address the genes that must exist but have not yet been recognized.

In the broadest sense, the key is understanding how humans get from a limited number of genes to the 1013 molecules that exist in the body, according to John McKearn, senior vice president and head of R&D at Pharmacia Corp. (PHA, Peapack, N.J.).