At what biological levels are data from single-celled organisms akin to a Rosetta stone for multicellular ones? To examine this question, we characterized a saturationmutagenized 67-kb region of the Drosophila genome by gene deletions, transgenic rescues, phenotypic dissections, genomic and cDNA sequencing, bio-informatic analysis, reverse transcription-PCR studies, and evolutionary comparisons. Data analysis using cDNA͞genomic DNA alignments and bioinformatic algorithms revealed 12 different predicted proteins, most of which are absent from bacterial databases, half of which are absent from Saccharomyces cerevisiae, and nearly all of which have relatives in Caenorhabditis elegans and Homo sapiens. Gene order is not evolutionarily conserved; the closest relatives of these genes are scattered throughout the yeast, nematode, and human genomes. Most gene expression is pleiotropic, and deletion studies reveal that a morphological phenotype is seldom observed when these genes are removed from the genome. These data pinpoint some general bottlenecks in functional genomics, and they reveal the acute emerging difficulties with data transferability above the levels of genes and proteins, especially with complex human phenotypes. At these higher levels the Rosetta stone analogy has almost no applicability. However, newer transgenic technologies in Drosophila and Mus, combined with coherency pattern analyses of gene networks, and synthetic neural modeling, offer insights into organismal function. We conclude that industrially scaled robogenomics in model organisms will have great impact if it can be realistically linked to epigenetic analyses of human variation and to phenotypic analyses of human diseases in different genetic backgrounds.Functional genomics is a widely used descriptor covering almost as many areas of research as it has interpretations. For metazoans, it encapsulates everything from the level of gene expression through morphogenesis to organismal phenotype. A major unknown in this huge field is the extent to which the processes giving rise to any metazoan phenotype are transferable from one organism to another. To examine this issue, we utilized Drosophila as the experimental organism and Saccharomyces cerevisiae, Caenorhabditis elegans, and Homo sapiens as the major comparators. We first characterized a substantial part of the fly X chromosome bracketed by the genes amnesiac and suppressor of forked (Fig. 1), obtained an overview of the mutational properties and phenotypes resulting from perturbations of this 2-megabase region (1), then focused on a 67-kb subregion that has been the ongoing focus of our laboratories (2-9) and that is anchored by the flightless locus. We now present the genomic and cDNA sequences for this region, the phenotypic analyses at the cellular and organismal levels after genetic, transgenic, and deficiency perturbations, and the evolutionary genomics. The data give an indication of the extent to which phenotypic predictions from model organisms to human beings are currently...