Cytogenetic and molecular characterization of heterochromatin gene models in Drosophila melanogaster.

In the past decade, genome-sequencing projects have yielded a great amount of information on DNA sequences in several organisms. The release of the Drosophila melanogaster heterochromatin sequence by the Drosophila Heterochromatin Genome Project (DHGP) has greatly facilitated studies of mapping, molecular organization, and function of genes located in pericentromeric heterochromatin. Surprisingly, genome annotation has predicted at least 450 heterochromatic gene models, a figure 10-fold above that defined by genetic analysis.

The paradox of functional heterochromatin.

Although heterochromatin has been studied for 80 years, its genetic function and molecular organization have remained elusive. In almost all organisms, heterochromatin has been regarded as genetically inactive chromosome regions. However, from genetic and genomic studies in Drosophila melanogaster and other organisms including humans, it is now clear that transcriptionally active domains are present within constitutive heterochromatin.

FISH analysis of Drosophila melanogaster heterochromatin using BACs and P elements.

The heterochromatin of chromosomes 2 and 3 of Drosophila melanogaster contains about 30 essential genes defined by genetic analysis. In the last decade only a few of these genes have been molecularly characterized and found to correspond to protein-coding genes involved in important cellular functions. Moreover, several predicted genes have been identified by annotation of genomic sequence that are associated with polytene chromosome divisions 40, 41 and 80 but their locations on the cytogenetic map of the heterochromatin are still uncertain.

Vital genes in the heterochromatin of chromosomes 2 and 3 of Drosophila melanogaster.

Heterochromatin has been traditionally regarded as a genomic wasteland, but in the last three decades extensive genetic and molecular studies have shown that this ubiquitous component of eukaryotic chromosomes may perform important biological functions. In D. melanogaster, about 30 genes that are essential for viability and/or fertility have been mapped to the heterochromatin of the major autosomes.