Scientists Compare Twelve Fruit Fly Genomes
Fly Consortium Uncovers Swarm of Novel Findings About Genomic
Evolution, Function
An international research consortium of scientists, supported
by the National Human Genome Research Institute (NHGRI), part of
the National Institutes of Health (NIH), today announced publications
comparing the genome sequences of 12 closely related fruit fly
species, 10 of which were sequenced for the first time. The analyses
identify thousands of novel genes and other functional elements
in the insects’ genomes, and describe how evolution has shaped
the genomes of these important models for genetic research.
"This remarkable scientific achievement underscores the value
of sequencing and comparing many closely related species, especially
those with great potential to enhance our understanding of fundamental
biological processes," said Francis S. Collins, M.D., Ph.D.,
director of NHGRI. "Thanks to the consortium’s hard work,
scientists around the world now have a rich new source of genomic
data that can be mined in many different ways and applied to other
important model systems as well as humans."
The fruit fly is one of the most important model organisms in
genetic research. In studies dating back nearly a century, researchers
used fruit flies to discover the basic rules of inheritance and
to study how a single cell, the fertilized egg, develops into a
whole animal. Because fruit flies are easy to work with in laboratory
settings, they continue to be used as a model to study fundamental
biological processes that occur in many living things, including
humans.
Although fruit flies have a genome that is 25 times smaller than
the human genome, many of the flies’ genes correspond to those
in humans and control the same biological functions. In recent
years, fruit fly research has led to discoveries related to the
influence of genes on diseases, animal development, population
genetics, cell biology, neurobiology, behavior, physiology and
evolution.
In papers published in the journal Nature, the Drosophila Comparative
Genome Sequencing and Analysis Consortium compare the genome sequences
of Drosophila melanogaster, which was published in 2000,
and D. pseudoobscura, published in 2005, with the recently
sequenced genomes of D. sechellia, D. simulans, D.
yakuba, D. erecta, D. ananassae, D.
persimilis, D. willistoni, D. mojavensis, D.
virilis and D. grimshawi. In addition, two companion
manuscripts in today’s Nature were contributed by researchers
from the Laboratory of Cellular and Developmental Biology of the
National Institute of Diabetes and Digestive and Kidney Diseases,
at NIH.
The work was carried out by hundreds of scientists from more than
100 institutions in 16 countries. The sequencing of the 10 new
genomes was led by Agencourt Bioscience Corp., Beverly, Mass. Other
sequencing centers contributing to the sequencing were Washington
University School of Medicine, St. Louis, Mo., the Broad Institute
of MIT and Harvard, Cambridge, Mass., and the J. Craig Venter Institute,
Rockville, Md. The sequencing centers were funded as part of NHGRI’s
Large-Scale Sequencing Research Network.
To the average person, one fruit fly hovering around an overripe
banana looks pretty much like any other. Researchers found that,
at first glance, the genomes of the various types of fruit flies
appear quite similar. However, a more detailed examination reveals
that only 77 percent of the approximately 13,700 protein-coding
genes in D. melanogaster are shared with all of the other
11 species.
Scientists observed that different regions of the fruit fly genomes,
including protein-coding genes and gene families, are evolving
at different rates. For example, genes involved in taste and smell,
detoxification and metabolism, sex and reproduction, and immunity
and defense appear to be the most rapidly evolving in the fruit
fly genomes.
The findings suggest that these particular protein-coding genes
likely evolve in the fruit fly genome as a result of adaptation
to changing environments and sexual selection. For instance, the
fruit fly species D. sechellia, whose population lives
on the Seychelles islands in the Indian Ocean, is losing gustatory
(taste) receptors approximately five times faster than other fruit
fly species that generally encounter a more diverse set of foods
than those available on an island.
In a surprising finding, researchers found that the genes that
produce selenoproteins appear to be absent in the D. willistoni genome.
Selenoproteins are responsible for reducing excess amounts of the
mineral selenium, an antioxidant found in a variety of food sources.
Selenoproteins are present in all animals, including humans. D.
willistoni appears to be the first animal known to lack these
proteins. However, researchers suggest that D. willistoni may
possibly encode selenoproteins in a different way, opening a new
avenue for further research.
A project leader and co-author for the studies, William M. Gelbart,
Ph.D., of Harvard University in Cambridge, Mass., said "The
availability of the 12 fruit fly genomes resulted in a dramatic
increase in resolution allowing us to examine how evolution has
fine-tuned biological processes. Our work shows that discovery
power increases with the number of genomes available for comparison."
More than 40 companion manuscripts with further detailed analyses
are in current and forthcoming issues of Bioinformatics, BioMed
Central (BMC) Bioinformatics, BMC Evolution Biology, BMC
Genomics, Genetics, Genome Biology, Genome
Research, Journal of Insect Science, Molecular
Biology and Evolution, Nature Genetics, Public
Library of Science (PLoS) Genetics, PLoS One, Proceedings
of the National Academy of Sciences, and Trends in Genetics.
In addition to their analyses aimed at gaining a better understanding
of genomic evolution, consortium scientists used the 12 fruit fly
genomes to identify thousands of new genes and other functional
elements. This work will bolster efforts to find all functional
elements in the reference genome sequence of D. melanogaster.
"Comparing the 12 fruit fly genomes allowed us to recognize
evolutionary signatures characteristic of each function. These
signatures enabled us to distinguish and identify thousands of
new functional elements." said Manolis Kellis, Ph.D., of the
Massachusetts Institute of Technology in Cambridge, Mass., and
a co-author of the Nature papers.
Specifically, researchers used the evolutionary signals to discover
1,193 new protein-coding sequences and called into question 414
sequences previously reported as protein-coding genes in the D.
melanogaster genome sequence. In addition, they found hundreds
of novel functional elements across the 12 fruit fly genomes, including:
non-protein coding genes; regulatory elements involved in the control
of gene transcription; and DNA sequences that mediate the structure
and dynamics of chromosomes.
"Our analyses only represent a small portion of questions
that can be answered in the context of these 12 species," said
Andrew G. Clark, Ph.D., from Cornell University in Ithaca, N.Y.,
a co-author on the Nature papers. "Today’s findings
represent an important starting point for future research aimed
at understanding the function of the genome features we discovered
and their relevance to the human genome."
The fruit fly genome sequences and details about the information
encoded by these genomes are publicly available from the NHGRI-funded
FlyBase database project (http://flybase.bio.indiana.edu).
Flybase is a collaboration of Harvard University, Cambridge, Mass.;
Indiana University, Bloomington; and the University of Cambridge,
United Kingdom. The fruit fly genome sequences are also available
from NIH’s National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov).
NCBI distributes the sequence data to the European Molecular Biology
laboratory’s Nucleotide Sequence Database, EMBL-Bank (http://www.ebi.ac.uk/embl/index.html),
and the DNA Data Bank of Japan, DDBJ (www.ddbj.nig.ac.jp).
The 12 fruit fly species are available to the research community
through the NSF- supported Tucson Drosophila Species Stock Center
at the University of Arizona (http://stockcenter.arl.arizona.edu/).
NHGRI is one of 27 institutes and centers at the NIH, an agency
of the Department of Health and Human Services. The NHGRI Division
of Extramural Research supports grants for research and for training
and career development at sites nationwide. Additional information
about NHGRI can be found at its Web site, www.genome.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
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