Joe Caspermeyer, Media Relations Manager & Science Editor
(480) 727-0369 | joseph.caspermeyer@asu.edu
November 12, 2007
Big Buzz: Landmark fruit fly DNA study advances genetics
The humble fruit fly has played a lead role on the scientific stage for more than a century. Tiny picnic pests to us, flies from a single species, Drosophila melanogaster, have provided a bounty of Nobel Prize winning discoveries for researchers in the fields of genetics and developmental biology, and helped serve as models of human diseases such as Parkinson’s and cancer.
Now, in a set of papers published in the journal Nature, the Biodesign Institute’s Sudhir Kumar, along with colleagues Alan Filipski, Sonja Prohaska and Stuart Newfeld, participated in the largest comparative DNA analysis of higher organisms ever assembled. In all, the complete DNA sequences, or genomes, from a dozen different fruit fly species were assembled to understand the differences between species at the DNA level.
“One major motivation for sequencing the genomes of so many fruit flies is that they will invigorate development of new computer tools to find important DNA parts at a genome scale,” said Kumar. “Then, these tools can be adapted to understand the function of different parts of our own genomes to identify disease-causing genes as well as parts of the genome that allow us to adapt. In this sense, fly genomes act as bioinformatics model sets for human and primate genomes.”
Each fruit fly genome is made up of 130 million individual DNA chemical components, and comparing a dozen species at once was like putting together a billion piece DNA puzzle. More than 200 scientists were responsible for this massive DNA project, called the Drosophila Genomics Consortium. This four-year tour de force study focused on uncovering the genetic differences as the first step in comparing the ecology and behavior amongst the species.
For Kumar’s ASU team, participating in the study gave them a chance to contribute to the discovery of the DNA clues that may have led to uncovering the time-points in the very first branches in the evolutionary tree from when the different species arose.
Timing is everything
Kumar is one of the world’s leading experts in molecular clocks, a technique that uses DNA information to trace the evolutionary history of a species. When combined with carbon dating from fossils and other physical evidence, these DNA timepieces can provide a powerful estimate for when branches in an evolutionary tree first split.
“Our main interest was to pinpoint the order of divergence of species and the timing of their emergence,” said Kumar.
Species diverge from each other due to the accumulation of mutations (changes) in DNA over epochs of evolutionary time. Gradually, these mutations give rise to differences in groups of individuals. Kumar explains that data from past studies of DNA changes in fruit flies, scientists know that the DNA can mutate 10 times faster than in mammals.
“If you think about this 40-50 million year time of divergence being the most ancient split in these 12 genomes, that corresponds to almost 500 million years of evolution for vertebrates,” said Kumar. “For example, comparisons of these twelve genomes, is similar to the comparisons between humans and fish and all of their intermediates.”
By analyzing almost 10,000 genes from the 12 fly species, his team was able to give the best estimate of how different species are from each other at the genetic level. “This large number of genes we analyzed means much less uncertainty,” said Kumar. The team captured the branch lengths of the evolutionary tree, and the estimation of the timing of species separation.
Identifying these DNA changes over evolutionary time can also help scientists pinpoint the origins of human disease.
“Many human diseases are studied in model organisms like mice, zebrafish, and fruit flies because a large number of genes found in humans and flies have very similar functions and traits, said Kumar, who directs the institute’s Center for Evolutionary Functional Genomics and is also a professor in the School of Life Sciences.
Let’s talk about sex
With data in hand for the branches in the fruit fly evolutionary tree, the researchers next wanted to apply this new DNA information to a fundamental question of speciation: reproduction.
Sex is the most important difference between individuals in a species and the genes involved have long been suggested to be the most rapidly evolving. In a study led by National Institutes of Health investigators Brian Oliver and colleagues Yu Zhang, David Sturgill, and Michael Parisi, the group honed in on the differences in genes with known roles in fruit fly sex and reproduction.
“In this work Brian Oliver and his team compared the evolutionary change at the level of genome (DNA sequence) with the tempo of the change in the expression of genes (phenotypes),” said Kumar. “As fruit fly genomes become more and more different from each other with time, the expression of genes they code also becomes increasingly different.”
In an analysis of 2500 genes involved in fruit fly sex and reproduction, their analysis showed that the male genes evolve more rapidly than non-sex genes, particularly those responsible for sperm production. These results highlight sexual selection as a key driving force in genome and species evolution.
“With faster and cheaper technologies to obtain genome sequence, many of which are being developed in the Biodesign Institute, comparison of many full genomes will be a growing trend in studying genome function and evolution” said Kumar. “These genomic advances are now being translated into gene function because of our new ability to pinpoint when, in a life cycle, and where, in a growing embryo, different genes are used. Integrated analysis of these datasets presents a goldmine for determining how genes function and interact.” Kumar’s lab has developed one such Web tool called FlyExpress (www.flyexpress.net), a NIH-funded project, which is a worldwide resource for researchers investigating fruit fly gene expression patterns.
With the 12 fruit fly genome dataset complete, scientists now have a way to address many key evolutionary questions, such as how and when new traits in species first came to be. Scientists will continue to explore the dataset to gain further insight into Drosophila biology while identifying the common evolutionary themes relevant to the human genome.
