News: Scientists find a fingerprint of evolution across the human genome
- From: "Robert Karl Stonjek" <rstonjek@xxxxxxxxxxxxxx>
- Date: Wed, 9 Apr 2008 13:56:01 -0400 (EDT)
Scientists find a fingerprint of evolution across the human genome
The Human Genome Project revealed that only a small fraction of the 3
billion "letter" DNA code actually instructs cells to manufacture proteins,
the workhorses of most life processes. This has raised the question of what
the remaining part of the human genome does. How much of the rest performs
other biological functions, and how much is merely residue of prior genetic
events?
Scientists from Cold Spring Harbor Laboratory (CSHL) and the University of
Chicago now report that one of the steps in turning genetic information into
proteins leaves genetic fingerprints, even on regions of the DNA that are
not involved in coding for the final protein. They estimate that such
fingerprints affect at least a third of the genome, suggesting that while
most DNA does not code for proteins, much of it is nonetheless biologically
important - important enough, that is, to persist during evolution.
Conservation of genetic information
To gauge how critical a particular stretch of DNA is, biologists often look
at the detailed sequence of "letters" it consists of, and compare it with a
corresponding stretch in related creatures like mice. If the stretch serves
no purpose, the thinking goes, the two sequences will differ because of
numerous mutations since the two species last shared an ancestor. In
contrast, it's believed that the sequences of important genes will be
similar, or "conserved," in different species, because animals with
mutations in these genes did not survive. Biologists therefore regard
conserved sequences as a sign of biological importance.
To test for conservation, researchers need to find matching stretches in the
two species. This is relatively easy for stretches that "code" for proteins,
where scientists long ago learned the meaning of the sequence. For
"noncoding" regions, however, the comparison is often ambiguous. Even within
a gene, stretches of DNA that code for pieces of the target protein are
usually interspersed with much larger noncoding stretches, called introns,
that are removed from the RNA working copy of the DNA before the protein is
made.
Signs of splicing
Previous researchers assumed that mutations in the middle of introns do not
affect the final protein, so they simply accumulate. In the new work,
however, the researchers found signs that evolution rejects some types of
mutations even in these regions of the genome. Although the selection is
weak, "introns are not neutral," in their effect on survival, says CSHL
professor Michael Zhang, a bioinformatics expert who headed the research
team.
To look for selection, CSHL researcher Chaolin Zhang, a doctoral candidate
at Stony Brook University, looked in the human genome for a subtle
statistical imbalance in how often various "letters" appear. The researchers
attribute this imbalance to special short stretches of DNA that mark regions
to be removed. Unless these signal sequences are sprinkled throughout an
intron, the data suggest, it may not be properly spliced out, with
potentially fatal consequences. Other sequences must likewise be preserved
in the regions to be retained.
The scientists found a preference for some "letters" across intron regions,
and the opposite preference in coding regions. Together, these regions make
up at least a third of the genome, which is thus under selective pressure
during evolution. The result supports other recent studies that suggest
that, although most DNA does not code for proteins, much of it is
nonetheless biologically important.
In addition to demonstrating how splicing affects genetic evolution, the
statistical analysis identified possible signaling sequences, some that were
already known and others that are new. According to co-author Adrian
Krainer, a CSHL professor and splicing expert, "the exciting thing will be
to experimentally test whether these predicted elements are really true."
"RNA landscape of evolution for optimal exon and intron discrimination"
appears in the April 15, 2008 edition of the Proceedings of the National
Academy of Sciences. The paper is available online at
http://www.pnas.org_cgi_doi_10.1073_pnas.0801692105.
Source: Cold Spring Harbor Laboratory
http://www.physorg.com/news126893405.html
Posted by
Robert Karl Stonjek
.
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