ABSTRACT

T here is growing genomic evidence on clustering o f functionally related genes in eukaryotes. Recent studies in yeast show a correlation between the expression patterns o f adjacent and nonadjacent pairs o f genes and that a significant proportion o f the former are functionally related. A transcriptome-interactome correlation has provided global evidence that yeast genes with similar expression profiles are more likely to encode interacting proteins. Fi= nally, an analysis o f several sequenced eukaryotic genomes found that genes involved in the same pathways were clustered. Stoichiometric imbalances in macromolecular complexes can be a source o f dominant phenotypes. Here this “dosage balance hypothesis” is extended with the idea that in many instances the physical association o f eukaryotic genes might result from a mechanism selecting “modules” which ensure better coregulation, maintain the right stoichi= ometry o f complexes and facilitate evolution by gene duplication.