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Scientists fix bugs in our understanding of evolution
June 20, 2008What makes a human different from a chimp? Researchers from the European Molecular Biology Laboratory's European Bioinformatics Institute [EMBL-EBI] have come one important step closer to answering such evolutionary questions correctly. In the current issue of Science they uncover systematic errors in existing methods that compare genetic sequences of different species to learn about their evolutionary relationships. They present a new computational tool that avoids these errors and provides accurate insights into the evolution of DNA and protein sequences. The results challenge our understanding of how evolution happens and suggest that sequence turnover is much more common than assumed.
"Evolution is happening so slowly that we cannot study it by simply watching it. That's why we learn about the relationships between species and the course and mechanism of evolution by comparing genetic sequences," says Nick Goldman, group leader at EMBL-EBI.
The four letter code that constitutes the DNA of all living things changes over time; for example individual or several letters can be copied incorrectly [substitution], lost [deletion] or gained [insertion]. Such changes can lead to functional and structural changes in genes and proteins and ultimately to the formation of new species. Reconstructing the history of these mutation events reveals the course of evolution.
A comparison of multiple sequences starts with their alignment. Characters in different sequences that share common ancestry are matched and gains and losses of characters are marked as gaps. Since this procedure is computationally heavy, multiple alignments are often built progressively from several pairwise alignments. It is impossible, however, to judge if a length difference between two sequences is a deletion in one or an insertion in the other sequence. For correct alignment of multiple sequences, distinguishing between these two events is crucial. Existing methods, that fail to do that, lead to a flawed understanding of the course of evolution.
"Our new method gets around these errors by taking into account what we already know about evolutionary relationships," says Ari Löytynoja, who developed the tool in Goldman's lab. "Say we are comparing the DNA of human and chimp and can't tell if a deletion or an insertion happened. To solve this our tool automatically invokes information about the corresponding sequences in closely related species, such as gorilla or macaque. If they show the same gap as the chimp, this suggests an insertion in humans."
Findings achieved with the new technique suggest that insertions are much more common than assumed, while the frequency of deletions has been overestimated by existing methods. A likely reason for these systematic errors of other techniques is that they were originally developed for structural matching of protein sequences. The focus of molecular biology is shifting, however, and understanding functional changes in genomes requires specifically designed methods that consider sequences' histories. Such approaches will likely reveal further bugs in our understanding of evolution in future and might challenge the conventional picture of sequence evolution.
European Molecular Biology Laboratory
A comparison of multiple sequences starts with their alignment. Characters in different sequences that share common ancestry are matched and gains and losses of characters are marked as gaps. Since this procedure is computationally heavy, multiple alignments are often built progressively from several pairwise alignments. It is impossible, however, to judge if a length difference between two sequences is a deletion in one or an insertion in the other sequence. For correct alignment of multiple sequences, distinguishing between these two events is crucial. Existing methods, that fail to do that, lead to a flawed understanding of the course of evolution.
"Our new method gets around these errors by taking into account what we already know about evolutionary relationships," says Ari Löytynoja, who developed the tool in Goldman's lab. "Say we are comparing the DNA of human and chimp and can't tell if a deletion or an insertion happened. To solve this our tool automatically invokes information about the corresponding sequences in closely related species, such as gorilla or macaque. If they show the same gap as the chimp, this suggests an insertion in humans."
Findings achieved with the new technique suggest that insertions are much more common than assumed, while the frequency of deletions has been overestimated by existing methods. A likely reason for these systematic errors of other techniques is that they were originally developed for structural matching of protein sequences. The focus of molecular biology is shifting, however, and understanding functional changes in genomes requires specifically designed methods that consider sequences' histories. Such approaches will likely reveal further bugs in our understanding of evolution in future and might challenge the conventional picture of sequence evolution.
European Molecular Biology Laboratory
Evolution Current Events and Evolution News RSSHuman genomics in China
Ten years ago, the Chinese National Human Genome Center at Shanghai (South Center, hereafter) was established in the Zhangjiang HiTech Park of Pudong District in Shanghai. To commemorate this important event, which marks the beginning of the Genomics Era in China, we specially organize a series of mini-reviews for this special issue.
Avian flu becoming more resistant to antiviral drugs, says University of Colorado study
A new University of Colorado at Boulder study shows the resistance of the avian flu virus to a major class of antiviral drugs is increasing through positive evolutionary selection, with researchers documenting the trend in more than 30 percent of the samples tested.
Spookfish uses mirrors for eyes
A remarkable new discovery shows the four-eyed spookfish to be the first vertebrate ever found to use mirrors, rather than lenses, to focus light in its eyes.
Study Yields Clues About the Evolution of Epilepsy
Two children have a seizure. One child never has another seizure. Twenty years later, the other child has a series of seizures and is diagnosed with epilepsy. A study being led by researchers at Rensselaer Polytechnic Institute is looking at what could possibly happen in the development of these two children that would lead to such extreme variations in their neurologic health.
Plant polymerases IV and V are special forms of Polymerase II
It's a little like finding out that Superman is actually Clark Kent. A team of biologists at Washington University in St. Louis has discovered that two vital cellular components, nuclear RNA Polymerases IV and V (Pol IV and V), found only in plants, are actually specialized forms of RNA Polymerase II, an essential enzyme of all eukaryotic organisms, including humans.
Four, three, two, one . . . pterosaurs have lift off
Pterosaurs have long suffered an identity crisis. Pop culture heedlessly -- and wrongly -- lumps these extinct flying lizards in with dinosaurs. Even paleontologists assumed that because the creatures flew, they were birdlike in many ways, such as using only two legs to take flight.
Research team reports how, when life on Earth became so big
In 3.5 billion years, life on earth went from single microscopic cells to giant sequoias and blue whales. Scientists have now documented quantitatively that the increase in maximum size of organisms was not gradual, but happened in two distinct bursts "tied to the geological evolution of the planet," said Michal Kowalewski, professor of geosciences at Virginia Tech.
Snails and humans use same genes to tell right from left
Biologists have tracked down genes that control the handedness of snail shells, and they turn out to be similar to the genes used by humans to set up the left and right sides of the body.
CSHL scientists discover new way in which ubiquitin modifies transcriptional machinery to regulate gene activity
During gene transcription - the process inside the nucleus of cells by which DNA, the genetic material, is copied into RNA - a large, ever-changing multiprotein complex is enlisted to assist the DNA-copying enzyme in its challenging job.
No quick or easy technological fix for climate change, researchers say
Global warming, some have argued, can be reversed with a large-scale "geoengineering" fix, such as having a giant blimp spray liquefied sulfur dioxide in the stratosphere or building tens of millions of chemical filter systems in the atmosphere to filter out carbon dioxide.
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