Surprises in fly genome

Surprises in fly genome
Comparative genome sequencing of 12 Drosophila species reveals new genes, gene structures, and regulators

Even after decades of genetic study, the Drosophila melanogaster genome still contains undiscovered genes and other genetic elements, according to a study in this week's Nature.

By comparing evolutionary signatures in the genome sequences of 12 Drosophila species, the authors found new protein-coding, RNA, and microRNA genes, as well as gene regulators and targets. They also discovered that several unusual translation mechanisms -- including skipped stop codons and reading-frame shifts -- are more common than previously thought.

Accompanying research papers in Nature this week present an overview of Drosophila genome evolution, as well as new findings in Drosophila sex chromosomes and sex-biased gene expression.

Finding new protein-coding genes in an organism as well-studied as D. melanogaster is "an interesting surprise," said Elliott Margulies of the National Human Genome Research Institute in Rockville, Md., who was not involved in the work.

Scientists led by four researchers -- Alexander Stark, Michael Lin, and Pouya Keradpour of the Broad Institute of MIT and Harvard in Cambridge, Mass., and Jakob Pedersen of the University of Copenhagen -- examined the 12 Drosophila sequences for evidence of regions that have been under natural selection. They scanned the genomes for unique evolutionary signatures associated with each type of genetic element. For example, conserved protein-coding regions usually show base changes that do not affect amino-acid sequence, while RNA genes allow mutations that preserve base-pairing interactions and microRNA genes show strong conservation only in certain parts of their sequences.

This approach "kicks up a notch the kind of comparative genomics that you can do," Margulies said. While most previous comparative studiesonly allowed researchers to determine whether a given region went through selection, using these signatures identifies what type of element it likely is.

The analysis predicted about 1,200 novel protein-coding exons in the Drosophila genome, corresponding to 150 new genes. Their results led to the revision of hundreds of gene transcription and translation models, which senior author Manolis Kellis of the Broad Institute said will be reflected in the next version of the annotated Drosophila genome at FlyBase.

The authors found evidence of several unusual gene structures in the fly, such as stop-codon readthough, in which a stop codon is misread or skipped, and poly-cistronic genes, which code for two or more distinct proteins. They also found that the Drosophila genome contains several instances of "programmed" changes in the reading frame of translation, which alters how messenger RNA is read into protein. All of these discoveries were "really unexpected," Kellis told The Scientist. "Many protein-coding genes don't actually follow the rules you would expect them to follow."

According to Ross Hardison of Pennsylvania State University in University Park, who was not involved in the work, these gene structures were thought to be very rare. "The importance of them becomes more obvious when you see multiple examples of them in a genome-wide study," he said.

The comparative analyses uncovered new microRNA genes, RNA genes, and RNA structures involved in post-transcriptional processes such as messenger RNA editing and translational control. They also revealed many new gene regulators, including several found at higher levels in specific tissues than regulators already known to be important in these tissues.

Their ability to add so much information to D. melanogaster annotated genome through comparative genomics shows "how powerful these methods are," Kellis said.

Melissa Lee Phillips
mail@the-scientist.com


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