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Science Forum Index » Bio Evolution Forum » Paper: Evolutionary Influences on Proteins [Open Access]
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| Robert Karl Stonjek |
 Posted: Wed Feb 14, 2007 8:49 am |
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Selected PLoS Biology research articles are accompanied by a synopsis
written for a general audience to provide non-experts with insight into the
significance of the published work.
Evolutionary Influences on Proteins
Rachel Jones
Citation: Jones R (2007) Evolutionary Influences on Proteins. PLoS Biol
5(2): e26 doi:10.1371/journal.pbio.0050026
Published: February 6, 2007
Copyright: © 2007 Public Library of Science. This is an open-access article
distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.
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The strings of amino acids that make up a protein are specified by the
sequence of nucleotides in the coding region of a gene. However, genes also
contain nucleotides that don't contribute to the sequence of a protein, in
noncoding areas called introns. Before the protein can be generated, the
introns must be removed and the coding parts (called exons) must be spliced
back together.
Splice-enhancer domains-exon sequences near the intron-exon boundary-help to
ensure that genes are spliced at the correct points. They also code for
specific amino acids within the protein, indicating that they must serve two
functions. In a new study, Joanna Parmley, Laurence Hurst, and colleagues
asked what effect this dual functionality has on the evolution of these
sequences. They found evidence that the necessity for splice enhancers near
the intron-exon boundaries causes these sequence regions to evolve at a
lower-than-average rate. The region near to intron-exon boundaries is also
more likely than expected to contain nucleotide sequences that are used in
splice-enhancer regions-a condition that results in a skewed amino acid
content in the corresponding parts of the encoded proteins. Thus, the amino
acid sequence of a protein might depend not only on its biological function,
but also on the presence of splice enhancers.
The authors began by analyzing the use of different amino acids near
intron-exon boundaries. Most amino acids were either more or less abundant
than expected by chance in these regions. The more-abundant ones were
encoded by nucleotide sequences found in splice enhancers. When the authors
analyzed amino acids that can be encoded by several different triplets of
nucleotides (each amino acid is encoded by three nucleotides), they found
that the increased abundance of the amino acids probably resulted from a
preference for specific nucleotides, rather than a direct preference for
those amino acids.
Before a transcribed gene is translated into the amino acids of its encoded
protein, noncoding intron sequences are removed and the remaining coding
exons are spliced together.
If there is selection pressure to conserve splice enhancers-that is, if the
splice enhancers confer some sort of evolutionary or fitness benefit and
thus are preserved by natural selection-one would expect these regions to
evolve more slowly than other parts of the genetic sequence. By comparing
splice-enhancer sequences in mouse and human genes, the authors showed that
the sequences are in fact conserved-and that smaller exons, in which more of
the nucleotides are close to an intron-exon boundary, also evolve more
slowly.
The rate of evolution of a protein is also constrained by other factors. For
example, "housekeeping" genes-those whose proteins are essential for
cellular function and are expressed in many tissues-tend to evolve slowly,
whereas nonessential genes (whose functions might be reproduced by another,
similar genes) often evolve more quickly. The results of this study show
that the proportion of a gene that falls near intron-exon boundaries has a
strong effect on the rate of protein evolution when compared with these
other factors.
An interesting insight into the possible functional effects of splice
enhancers comes from looking at genes that have lost their introns. Such
genes show markedly accelerated evolution in the regions that originally
flanked intron-exon boundaries. This indicates that a selection
constraint-presumably to maintain correct splicing by conserving
splicing-enhancer domains-has been released following the loss of introns
(because the splice enhancers are no longer needed). is finding also implies
that the need to conserve the splice enhancers in the original proteins
meant that the proteins were not optimized for their biological functions,
but rather might have evolved a "compromise" sequence that could fulfil both
roles.
The idea that the evolution of a gene can be so strongly influenced by
something other than the biology of the protein it encodes is an intriguing
one that might have consequences for gene therapy and for protein
engineering, as well as for our understanding of protein evolution. Further
work will be required to investigate whether other features, apart from
splice-enhancer regions, also influence nucleotide and amino acid use near
the boundaries between coding and noncoding gene segments.
Source: PLoS Biology [Open Access]
http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050026
Posted by
Robert Karl Stonjek |
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