Navigation Links
Errors in protein structure sparked evolution of biological complexity

Over four billion years of evolution, plants and animals grew far more complex than their single-celled ancestors. But a new comparison of proteins shared across species finds that complex organisms, including humans, have accumulated structural weaknesses that may have actually launched the long journey from microbe to man.

The study, published in Nature, suggests that the random introduction of errors into proteins, rather than traditional natural selection, may have boosted the evolution of biological complexity. Flaws in the "packing" of proteins that make them more unstable in water could have promoted protein interactions and intracellular teamwork, expanding the possibilities of life.

"Everybody wants to say that evolution is equivalent to natural selection and that things that are sophisticated and complex have been absolutely selected for," said study co-author Ariel Fernndez, PhD, a visiting scholar at the University of Chicago and senior researcher at the Mathematics Institute of Argentina (IAM) in Buenos Aires. "What we are claiming here is that inefficient selection creates a niche or an opportunity to evolve complexity."

"This is a novel bridge between protein chemistry and evolutionary biology," said co-author Michael Lynch, PhD, professor of biology at Indiana University. "I hope that it causes us to pause and think about how evolution operates in new ways that we haven't thought about before."

When mildly negative mutations arise in a species with a large population, such as the trillions of bacterial organisms that can fill a small area, they are quickly cleared out by selective forces. But when a new mutation appears in a species with a relatively small population, as in large mammals and humans, selection against the error is slower and less efficient, allowing the mutation to spread through the population.

To look at whether these mild defects accumulate in species with small populations, Fernndez and Lynch compared over 100 proteins shared by 36 species of varying population size. Though these shared, "orthologous" proteins are identical in shape and function, genetic differences alter them in more subtle ways.

Fernndez and Lynch focused on design flaws called "dehydrons," sites where the protein structure is vulnerable to chemical reactions with water. Proteins with more dehydrons are more "unwrapped" - unstable in an aqueous environment, and therefore prone to bind with another protein to protect their vulnerable regions.

A computational analysis of 106 orthologous proteins confirmed their hypothesis that proteins from species with smaller populations were more vulnerable in water. The result suggests that structural errors accumulate in large organisms such as humans due to random genetic drift.

"We hate to hear that our structures are actually lousier," Fernndez said. "But that has a good side to it. Because they are lousier, they are more likely to participate in complexes, and we have a much better chance of achieving more sophisticated function through teamwork. Instead of being a loner, the protein is a team player."

On their own, these unstable proteins might be expected to perform their cellular duties more poorly, possibly causing harm to the organism. But unstable proteins are also "stickier," more likely to form associations with other proteins that could introduce more flexibility and complexity into the cell. If these complexes create a survival advantage for the organism, forces of natural selection should take over and spread the new protein complex through the population.

"It's not an argument against selection, it's an argument for non-adaptive mechanisms opening up new evolutionary pathways that wouldn't have been there before," Lynch said. "It's those first little nicks getting into the protein armor that essentially open up a new selective environment."

To confirm that the accumulation of structural flaws in proteins preceded, rather than resulted from, the formation of complexes, Fernndez and Lynch turned to a natural experiment. Some bacterial species have two types of populations: communities that live inside other organisms and larger populations living free in the environment. When orthologous proteins were compared between these two populations, the same pattern emerged proteins from the smaller populations were more flawed than those from the free-living bacteria of the same species.

Despite these accidental benefits, the accumulation of too many structural flaws can be dangerous to an organism. When highly reactive proteins such as prions, amyloid-beta, or tau are too sticky, they can clump into aggregates that kill cells and cause diseases such as Alzheimer's and encephalopathy.

The implication that complexity initially arose by accident may be provocative within the field of evolutionary biology, the authors said. The discovery that flawed proteins are more likely to form complexes could also revolutionize the growing field of bioengineering, where the tools of evolution are used to create stronger, self-assembling, or self-reparing materials.

"Natural designs are often one notch more sophisticated than the best engineering," Fernndez said. "This is another example: Nature doesn't change the molecular machinery, but somehow it tinkers with it in subtle ways through the wrapping."


Contact: Robert Mitchum
University of Chicago Medical Center

Related biology technology :

1. Brain regions can take short naps during wakefulness, leading to errors
2. Drug Interaction Tool Offered Free in Response to Increasing At-Home Deaths From Medication Errors
3. Dont Believe What You Hear on Countdown: Keith Olbermanns Factual Errors
4. Pfenex Inc., Through Its Reagent Proteins Business Division, Announces Submission of Biologics Master File for Recombinant CRM197 to US FDA
5. Intrinsic Bioprobes Launches Three New CLIA Approved Mass Spectrometry-Based Tests for Proteins Implicated in Kidney Disease and Renal Failure
6. New test to study proteins involved in neurodegenerative diseases
7. OriGene Releases Bioactive Full-length Human MTOR Protein
8. Reportlinker Adds Therapeutic Proteins to 2014
9. Caliper Life Sciences Launches Microfluidic LabChip® DS Platform for UV/VIS Spectral Analysis of Nucleic Acid and Protein Samples
10. Reportlinker Adds The 2011 Immunoprotein Diagnostics Market: US, Europe, Japan Test Volume and Sales Forecasts by Country and Market Segment
11. BioInformatics, LLC New Market Report - Membrane Protein Structure
Post Your Comments:
(Date:11/27/2015)... ... November 27, 2015 , ... ... that includes over 2,000 technical presentations offered in symposia, oral sessions, workshops, awards, ... spectroscopy, covers a wide range of applications such as, but not limited to, ...
(Date:11/26/2015)... , November 26, 2015 /PRNewswire/ ... --> Accutest Research Laboratories, ... Contract Research Organization (CRO), has formed ... Cancer Center - Temple Health for ... ,     (Photo: ) , ...
(Date:11/25/2015)... November 26, 2015 ... Market 2016 - 2020 report analyzes that automating ... and quality in long-term samples, minimizing manual errors, ... Automation minimizes manual errors such as mislabeling or ... Further, it plays a vital role in blood ...
(Date:11/25/2015)... 2 nouvelles études permettent d , identifier ... souches bactériennes retrouvées dans la plaque dentaire des ... Ces recherches  ouvrent une nouvelle voie ... l,un des problèmes de santé les plus fréquemm ... --> 2 nouvelles études permettent d , ...
Breaking Biology Technology:
(Date:11/12/2015)... 2015   Growing need for low-cost, easy ... been paving the way for use of biochemical ... analytes in clinical, agricultural, environmental, food and defense ... in medical applications, however, their adoption is increasing ... continuous emphasis on improving product quality and growing ...
(Date:11/10/2015)... Nov. 10, 2015  In this report, ... basis of product, type, application, disease indication, ... this report are consumables, services, software. The ... safety biomarkers, efficacy biomarkers, and validation biomarkers. ... are diagnostics development, drug discovery and development, ...
(Date:11/9/2015)... Nov. 09, 2015 ... of the "Global Law Enforcement Biometrics ... --> ) has announced ... Enforcement Biometrics Market 2015-2019" report to ... Markets ( ) has announced the ...
Breaking Biology News(10 mins):