Navigation Links
Various species' genes evolve to minimize protein production errors

CAMBRIDGE, Mass. -- Scientists at Harvard University and the University of Texas at Austin have found that genetic evolution is strongly shaped by genes' efforts to prevent or tolerate errors in protein production.

Their study also suggests that the cost of errors in protein production may lie in the malformed proteins themselves, rather than the loss of functional proteins. Misfolded proteins can build up in long-lived cells, like neurons, and cause neurodegenerative diseases.

The work, by D. Allan Drummond at Harvard and Claus O. Wilke at Texas, is described in the July 25 issue of the journal Cell.

"It has long been believed that the main force of natural selection on protein-coding genes is the need to maintain a working protein," says Drummond, a Bauer Fellow in Harvard's FAS Center for Systems Biology. "Our work suggests that another force may be equally important: the need to avoid misfolded proteins resulting from errors in translation."

Protein molecules must fold to become biologically active, and mistakes can cause misfolding, which can be toxic. Yet the protein-producing factories in our cells are estimated to make mistakes in 20 percent of the molecules they produce. Adaptations to this surprising sloppiness may be crucial in understanding the evolution of genes across species, from bacteria to humans, say Drummond and Wilke.

Essentially, they write, natural selection has fostered the evolution of genes that minimize the effects of errors in translation, the production of proteins from genetic templates in cells. An example is the careful placement of codons, which are sections of DNA that code for amino acids, the building blocks of proteins. Some codons translate more accurately, and previous research had suggested that high-fidelity codons are positioned at key locations in the genome, where a mistake might be harmful. These studies, however, had only considered fast-growing organisms like E. coli bacteria and fruit flies.

"Contrary to what was believed, our work shows that even in the human genome, codons are positioned to minimize errors," says Wilke, assistant professor of integrative biology at Texas. "Just like a mistake on your taxes is more costly than a mistake on your grocery list -- so you concentrate more on your taxes -- cells seem to concentrate on preventing mistakes that might result in costly misfolded proteins."

Drummond and Wilke analyzed humans, mice, fruit flies, worms, yeast and E. coli bacteria and discovered that all of these organisms have evolved ways to prevent the production of costly aberrant proteins.

"Finding such sweeping effects from a single, simple cost has the potential to reshape the way evolution is studied at the molecular level," Drummond says. "While much work has focused on how evolution makes creatures different, our work emphasizes fundamental ways in which all life is the same."

While evolutionary studies are often retrospective, Drummond and Wilke also developed a molecular-level evolutionary simulation, allowing them to track the evolution of genomes encoding many simple proteins over millions of generations. In some simulations, they added evolutionary costs for misfolded proteins, while in others this cost was not factored in. They found that genomes evolving with misfolding costs developed all the genome-wide patterns seen in real organisms, while those evolving without costs did not.

The work could have long-term implications for our understanding of neurodegenerative diseases. Misfolded proteins are known to accumulate in neurons and are central players in fatal disorders such as amyotrophic lateral sclerosis, better known as Lou Gehrig's disease. Drummond and Wilke suggest that mistranslation may contribute to long-studied forms of ALS and other similar diseases.

Wilke says the current study may lead to better ways to detect genes with mutations that lead to production of toxic, misfolded proteins, and ultimately, to a better understanding of neurodegenerative disease.

"These genes may produce proteins that look innocuous but nevertheless cause a severe disease condition," Wilke says.


Contact: Steve Bradt
Harvard University

Related biology news :

1. Study suggests past climate changes may have promoted the formation of new species in the Amazon
2. Global warming experts recommend drastic measures to save species
3. From humming fish to Puccini: Vocal communication evolved with ancient species
4. Incentives for carbon sequestration may not protect species
5. Setting the record right: species diversity less dramatic than previously believed
6. Species have come and gone at different rates than previously believed
7. Census of Marine Life lists 122,500 known species, over halfway to complete inventory by Oct. 2010
8. New bee checklist lets scientists link important information about all bee species
9. World-class environment vision to bring back the species
10. First successful reverse vasectomy on endangered species performed at the National Zoo
11. Threatened or invasive? Species fates identified
Post Your Comments:
(Date:11/9/2015)... , Nov. 09, 2015 ... the addition of the "Global Law ... their offering. --> ) ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) has ...
(Date:11/2/2015)... , Nov. 2, 2015  SRI International has been ... provide preclinical development services to the National Cancer Institute ... will provide scientific expertise, modern testing and support facilities, ... preclinical pharmacology and toxicology studies to evaluate potential cancer ... The PREVENT Cancer Drug Development Program is an ...
(Date:10/29/2015)... Oct. 29, 2015 Daon, a global leader ... has released a new version of its IdentityX ... North America have already installed IdentityX ... includes a FIDO UAF certified server component ... to activate FIDO features. These customers include some of ...
Breaking Biology News(10 mins):
(Date:11/27/2015)... November 27, 2015 ... popularity of companion diagnostics is one of ... market with pharmaceutical companies and diagnostic manufacturers ... tests. . --> ... report on global cancer biomarkers market spread ...
(Date:11/25/2015)... , Nov. 25, 2015  PharmAthene, Inc. (NYSE MKT: ... adopted a stockholder rights plan (Rights Plan) in an ... loss carryforwards (NOLs) under Section 382 of the Internal ... --> PharmAthene,s use of its NOLs could be ... as defined in Section 382 of the Code. In ...
(Date:11/25/2015)... , Nov. 25, 2015  Neurocrine Biosciences, Inc. ... Gorman , President and CEO of Neurocrine Biosciences, will ... Conference in New York . ... visit the website approximately 5 minutes prior to the ... replay of the presentation will be available on the ...
(Date:11/25/2015)... 2015 The Global Genomics ... professional and in-depth study on the current state ... ) , The report ... definitions, classifications, applications and industry chain structure. The ... markets including development trends, competitive landscape analysis, and ...
Breaking Biology Technology: