LARGE-SCALE TAXONOMIC PROFILING OF EUKARYOTIC MODEL ORGANISMS - A COMPARISON OF ORTHOLOGOUS PROTEINS ENCODED BY THE HUMAN, FLY, NEMATODE, AND YEAST GENOMES

Comparisons of DNA and protein sequences between humans and model orga nisms, including the yeast Saccharomyces cerevisiae, the nematode Caen orhabditis elegans, and the Fruit fly Drosophila melanogaster, are a s ignificant source of information about the function of human genes and proteins in both normal and disease states, Important questions regar ding cross-species sequence comparison remain unanswered, including (1 ) the fraction of the metabolic, signaling, and regulatory pathways th at is shared by humans and the various model organisms; and (2) the va lidity of functional inferences based on sequence homology. We address ed these questions by analyzing the available fractions of human, fly, nematode, and yeast genomes for orthologous protein-coding genes, app lying strict criteria to distinguish between candidate orthologous and paralogous proteins. Forty-two quartets of proteins could be identifi ed as candidate orthologs, Twenty-four Drosophila protein sequences we re more similar to their human orthologs than the corresponding nemato de proteins. Analysis of sequence substitutions and evolutionary dista nces in this data set revealed that most C. elegans genes are evolving more rapidly than Drosophila genes, suggesting that unequal evolution ary rates may contribute to the differences in similarity to human pro tein sequences. The available fraction of Drosophila proteins appears to lack representatives of many protein families and domains, reflecti ng the relative paucity of genomic data From this species.