Analysis of expressed sequence tags indicates 35,000 human genes

The number of protein-coding genes in an organism provides a useful first m easure of its molecular complexity. Single-celled prokaryotes and eukaryote s typically have a few thousand genes; for example. Escherichia coli(1) has 4,300 and Saccharomyces cerevisiae(2) has 6.000. Evolution of multicellula rity appears to have been accompanied by a several-fold increase in gene nu mber, the invertebrates Caenorhabditis elegans(3) and Drosophila melanogast er(4) having 19,000 and 13,600 genes, respectively. Here we estimate the nu mber of human genes by comparing a set of human expressed sequence tag (EST ) contigs with human chromosome 22 and with a non-redundant set of mRNA seq uences. The two comparisons give mutually consistent estimates of approxima tely 35,000 genes, substantially lower than most previous estimates. Evolut ion of the increased physiological complexity of vertebrates may therefore have depended more on the combinatorial diversification of regulatory netwo rks or alternative splicing than on a substantial increase in gene number.