Changes in gene order and gene expression

Studies on changes in gene position in germ line and somatic cell chromosomes during evolution and differentiation have led biologists to abandon the static view of chromosomes as invariant linear arrays of hereditary information. Prokaryotic cells contain several classes of DNA insertion elements which move from place to place in the genome and mediate chromosome rearrangements. Similar elements exist in a wide variety of eukaryotic organisms (yeasts, insects, plants, and vertebrates). In addition, both reversible and irreversible changes of chromosome primary structure provide developmental controls on gene activity in bacteria, bacteriophages, yeasts, trypanosomes, and mammalian lymphocytes. At least five recombination mechanisms are known to catalyze chromosome changes: 1) general homologous, 2) site-specific reciprocal, 3) illegitimate, 4) DNA splicing, and 5) replicative. Various combinations of these mechanisms can explain many different chromosome rearrangements and changes in gene dosage. Changes in gene position can alter gene expression in many ways, some of which we understand (such as insertional mutation and inversion of coding and regulatory sequences) and some of which are still unexplained. The activities of DNA insertion elements and somatic rearrangement systems are subjects to controls at several levels by specific regulatory systems, natural selection, and connection to cell lineage. Despite the recent increase in knowledge about the biological importance of changes in gene order on chromosomes, there are far more questions than answers, particularly about the mechanisms that coordinate recombination events and cell division in higher organisms.