June 20, 2008 -- What 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.
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
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.
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
Source : European Molecular Biology Laboratory