SCIENCE

“Drosophila may be the single most thoroughly studied model organism; it allowed us to discover, a century ago, that chromosomes are the carriers of genetic information,” says Celniker, whose group studies the transcriptome. The transcriptome is the totality of RNA forms that transmit genetic information to the cellular machinery which constructs functioning proteins, as well as the noncoding RNAs that regulate gene expression, splicing, RNA stability, and metabolism. Yet, says Celniker, “there’s still a lot of undiscovered territory.”

Celniker’s transcriptome group succeeded in exploring Drosophila RNAs at a level never achieved before. “From the RNAs we identified approximately one thousand new genes, both protein-coding and noncoding. These were previously missed because they are less well conserved, or were found in less-studied developmental stages and RNA populations. Thus they tend to be expressed at lower levels than known genes.” She adds, “We also found an order-of-magnitude increase in the ways that genes are spliced and edited to produce alternate forms of known proteins, thus significantly increasing the complexity of the proteome.” The proteome is the set of all proteins expressed by the genome.

Karpen’s group studies chromatin, the combination of DNA and proteins that organize an organism’s genome into chromosomes. In chromatin, the DNA is wound around structures called nucleosomes, made of histone proteins. Other proteins (and some RNA) in chromatin also affect its organization and function. Karpen says the group’s goal “is to define the distributions of chromatin proteins and how chemical modifications can change their function.” They have produced the first comprehensive picture of how patterns of chromatin components are associated with chromosome functions, including the active transcription of genes. These mechanisms are called “epigenetic” because their influence on genome function is coded by the associated proteins rather than the DNA sequence.

The modENCODE transcriptome and chromatin groups, working with other groups that concentrate on regulatory elements, small RNAs, and DNA replication, produced what Karpen calls a “groundbreaking, comprehensive analysis, which vastly increases the information about the Drosophila genome available to researchers and provides a foundation for in-depth functional studies.”

The research groups carried out their studies on four different kinds of Drosophila cells maintained in laboratory cell cultures, not all of which had been extensively explored before. Additional studies with whole animals were carried out, especially in tracking developmental changes, from fly embryos through larvae and pupae to adult males and females.