Human Proteins Evolving Slowly Thanks To Multitasking Genes

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Human Proteins Evolving Slowly Thanks To Multitasking Genes

http://www.sciencedaily.com/releases/2007/02/070206095832.htm

Many human proteins are not as good as they might be because the

gene sequences that code for them have a double role which slows

down the rate at which they evolve, according to new research

published in PLoS Biology.

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. (Credit: Hurst et al. /

PLoS Biology)

By tweaking these dual role regions, scientists could develop gene

therapy techniques that produce proteins that are even better than

those found in nature, and could one day be used to help people

recover from genetic disorders.

The stretch of DNA which codes for a specific protein is often

interrupted by sections of apparently useless DNA – known as

introns – which need to be edited out in order to produce a new

protein.

Recently it has been discovered that some of the instructions on

where to splice and re-splice the DNA in this editing process are

contained in the coding section, or exon, of the DNA itself.

So, as well as spelling out which amino acids are needed to produce

a specific protein, the part of the exon immediately next to the

intron contains information that is essential for the gene editing

process.

This means that these parts of genes evolve particularly slowly,

making the proteins they encode for not as good as they could be had

evolutionary processes been more able to improve them over time.

" Our research suggests that a gene with many exons would evolve at

under half the rate of the same one that had no introns, simply

owing to the need to specify where to remove introns, " said

Professor ce Hurst from the University of Bath (UK), who

worked with colleagues from the University of Lausanne (Switzerland)

on the project.

" This is one of the strongest predictors of rates of protein

evolution known, indicating that this dual coding role is vastly

more influential than previously believed. "

The finding could have major implications for medicine and the

development of gene therapy techniques in which people with a

defective gene are given the correct version.

" Our results suggest that we could make the replacement gene even

better than the normal version, " said Professor Hurst, from the

Department of Biology & Biochemistry at the University of Bath.

" We would just need to remove the introns and tweak the protein at

the sites that were dual coding.

" We also found that genes that have lost their introns many millions

of years ago evolve especially fast near where the introns once

resided.

" This indicates that this tweaking of the dual role sections of

genes is also what evolution does when introns are removed. "

The research was funded by the Biotechnology & Biological Sciences

Research Council, the Swiss National Science Foundation and the

Center for Integrative Genomics at the University of Lausanne.