The confirmation that there might be fewer than 30,000 protein-coding genes in the human genome is one of the key results of the monumental work presented in this issue of Science by Venter et al.(1). That a mere one-third increase in gene numbers could be enough to progress from a rather unsophisticated nematode [Caenorhabditiselegans, with about 20,000 genes (2)] to humans (and other mammals) is certainly quite provocative and will undoubtedly trigger scientific, philosophical, ethical, and religious questions throughout the beginning of this new century. By the same token, humans appear only five times as complex as a bacterium like Pseudomonas aeruginosa (3). Although a significant uncertainty is still attached to this low number (see below), it was not totally unexpected, after the downward trend initiated by the analysis of the first two complete human chromosomes (4, 5), as well as two independent statistical studies (6, 7), and the unexpectedly low (14,000) Drosophila gene number (8).

After the older C value paradox (9), we now have an apparent N value paradox on our hands: Neither the cellular DNA content (in mass) nor its gene content appears directly related to our intuitive perception of organismal complexity. However, logic taught us that paradoxes often arise from the use of imprecise or ambiguous terminology. In a quick (admittedly nonrepresentative) survey among people in my laboratory, the answers to the question:“How much more complex is a human compared to a nematode?” ranged from a mere 100 to near infinity. Those widely different opinions were mostly the result of the lack of an objective (physical) measurement of what we mean by “biological complexity.” Some only considered the diversity of cell types, others considered brain circuitry, and others went as far as including the cultural achievements of the human species as a whole. Thus, 30,000 human genes is not equally surprising to everybody.