Nav: Home

Beyond a 'speed limit' on mutations, species risk extinction

October 01, 2007

CAMBRIDGE, Mass. -- Harvard University scientists have identified a virtual "speed limit" on the rate of molecular evolution in organisms, and the magic number appears to be 6 mutations per genome per generation -- a level beyond which species run the strong risk of extinction as their genomes lose stability.

By modeling the stability of proteins required for an organism's survival, Eugene Shakhnovich and his colleagues have discovered this essential thermodynamic limit on a species's rate of evolution. Their discovery, published this week in the Proceedings of the National Academy of Sciences, draws a crucial connection between the physical properties of genetic material and the survival fitness of an entire organism.

"While mathematical genetics research has brought about some remarkable discoveries over the years, these approaches always failed to connect the dots between the reproductive fitness of organisms and the molecular properties of the proteins encoded by their genomes," says Shakhnovich, professor of chemistry and chemical biology in Harvard's Faculty of Arts and Sciences. "We've made an important step toward finally bridging the gap between macroscopic and microscopic biology."

According to Shakhnovich, crucial aspects of an organism's evolutionary fitness can be directly inferred by inspecting its DNA sequences and analyzing how the proteins encoded by those sequences fold. DNA sequences encode the order of amino acids in a protein, and amino acids act as the protein's basic building blocks by arranging themselves into a structure that allows the protein to perform its biological function.

The research was inspired in part by the longstanding recognition that knocking out essential genes, making them inactive, produces a lethal phenotype, or a physiologically unviable organism.

"From there, we made the simple assumption that in order for an organism to be viable, all of its essential genes -- those that support basic cell operations -- have to encode at least minimally stable proteins," says Shakhnovich. "What occurs over the long process of evolution is that random mutations can either encode slightly more or less stable proteins."

If enough mutations push an essential protein towards an unstable, non-functional structure, the organism will die. Shakhnovich's group found that for most organisms, including viruses and bacteria, an organism's rate of genome mutation must stay below 6 mutations per genome per generation to prevent the accumulation of too many potentially lethal changes in genetic material.

The existence of a mutation limit for viruses helps explain how the immune system can perform its function. Because viral replication and survival can only occur at a limited rate, the body has a window of time to develop antibodies against infectious agents. Furthermore, if the mutation rate is high, the size of the genome in question must be small to stay within the bounds of the speed limit -- thus organisms that tend to mutate quickly are those with concise genomes, such as viruses and bacteria.

The Shakhnovich speed limit also offers an explanation for observed differences in genome sizes between organisms with genome error correction -- such as bacteria, mammals, birds, and reptiles - and those without, such as RNA viruses: In more complex organisms, cells have evolved correction systems to detect and fix errors in DNA replication. These systems drastically reduce the number of mutations per replication, increasing the mutational stability of the genome and allowing more intricate and delicate biological systems to develop without the risk of interruptive mutations.

"It's an interesting corollary because it suggests that there is a fundamental tradeoff between evolutionary security and adaptive flexibility: Larger, more complex organisms have to have error correction to protect organismic viability, but this means the rate of evolution slows down significantly," Shakhnovich says. "As organisms become more complex, they have more to lose and can't be as radically experimental with their genomes as some viruses and bacteria."
-end-
Co-authors on the paper are Konstantin B. Zeldovich of the Department of Chemistry and Chemical Biology and Peiqiu Chen of the departments of Physics and of Chemical and Chemical Biology in Harvard's Faculty of Arts and Sciences. Their work is funded by the National Institutes of Health.

Harvard University

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

How the Immune System Works (The How it Works Series)
by Lauren M. Sompayrac (Author)

How the Immune System Works has helped thousands of students understand what’s in their big, thick, immunology textbooks. In his book, Dr. Sompayrac cuts through the jargon and details to reveal, in simple language, the essence of this complex subject.

In fifteen easy-to-read chapters, featuring the humorous style and engaging analogies developed by Dr. Sompayrac, How the Immune System Works explains how the immune system players work together to protect us from disease – and, most importantly, why they do it this way.

Rigorously updated for this fifth... View Details


The Immune System Recovery Plan: A Doctor's 4-Step Program to Treat Autoimmune Disease
by Susan Blum (Author), Mark Hyman (Foreword), Michele Bender (Foreword)

One of the most sought-after experts in the field of functional medicine shares her proven four-step program to treat, reverse, and prevent autoimmune conditions and repair your immune system.

• Are you constantly exhausted?

• Do you frequently feel sick?

• Are you hot when others are cold, or cold when everyone else is warm?

• Do you have trouble thinking clearly, aka “brain fog”?

• Do you often feel irritable?

• Are you experiencing hair loss, dry skin, or unexplained weight fluctuation?

• Do your joints ache or... View Details


The Immune System, 4th Edition
by Peter Parham (Author)

The Immune System, Fourth Edition emphasizes the human immune system and presents immunological concepts in a coherent, concise, and contemporary account of how the immune system works. Written for undergraduate, medical, veterinary, dental, and pharmacy students, it makes generous use of medical examples to illustrate points. This classroom-proven textbook offers clear writing, full-color illustrations, and section and chapter summaries that make the book accessible and easily understandable to students.

The Fourth Edition is a major revision that brings the content... View Details


Basic Immunology: Functions and Disorders of the Immune System, 5e
by Abul K. Abbas MBBS (Author), Andrew H. H. Lichtman MD PhD (Author), Shiv Pillai MBBS PhD (Author)

In this updated edition of Basic Immunology, the authors continue to deliver a clear, modern introduction to immunology, making this the obvious choice for today's busy students. Their experience as teachers, course directors, and lecturers helps them to distill the core information required to understand this complex field. Through the use of high-quality illustrations, relevant clinical cases, and concise, focused text, it's a perfectly accessible introduction to the workings of the human immune system, with an emphasis on clinical relevance.... View Details


The Immune System, 3rd Edition
by Peter Parham (Author)

The Immune System, Third Edition emphasizes the human immune system and synthesizes immunological concepts into a comprehensible, up-to-date, and reader-friendly account of how the immune system works. 

Written for undergraduate, medical, veterinary, dental, and pharmacy students in immunology courses, it makes generous use of medical examples to illustrate points. 

The Third Edition has been extensively revised and updated and includes two new chapters on innate and adaptive immunity, which explore the physical, cellular, and molecular principles... View Details


Immune System: 101 Natural Ways to Boost your Immune System, Fight Germs, and Live a Healthy Life
by Living in Health (Author)

BOOST YOUR IMMUNE SYSTEM! 101 NATURAL WAYS TO BOOST YOUR IMMUNE SYSTEM, FIGHT GERMS, AND LIVE A HEALTHY LIFE Your immune system is the body’s only line of defense against both foreign and internal threats. It is clear therefore that you must maintain your immune system in the best possible condition for optimal health. It is not a myth that some foods are better than others at boosting our immunity. If you were ever wondering what might be the best foods in the world to help keep your immune system in the best shape, then this book is simply the way to go. It really helps to have a great... View Details


The Immune System: A Very Short Introduction (Very Short Introductions)
by Paul Klenerman (Author)

The immune system is central to human health and the focus of much medical research. Growing understanding of the immune system, and especially the creation of immune memory (long lasting protection), which can be harnessed in the design of vaccines, have been major breakthroughs in medicine.

In this Very Short Introduction, Paul Klenerman describes the immune system, and how it works in health and disease. In particular he focuses on the human immune system, considering how it evolved, the basic rules that govern its behavior, and the major health threats where it is... View Details


Immune: How Your Body Defends and Protects You (Bloomsbury Sigma)
by Catherine Carver (Author)

The human body is like an exceedingly well-fortified castle, defended by billions of soldiers--some live for less than a day, others remember battles for decades, but all are essential in protecting us from disease. This hidden army is our immune system, and without it we could not survive the eternal war between us and our microscopic enemies.

Immune explores the incredible arsenal that lives within us--how it knows what to attack and what to defend, and how it kills everything from the common cold to the plague bacterium. We see what happens when the immune system turns on... View Details


The Immune System Cure: Optimize Your Immune System in 30 Days-The Natural Way!
by Lorna Vanderheaghe (Author)

What causes one person to catch a cold or flu and another to avoid it? Why do serious outbreaks of infectious diseases leave some individuals untouched? What allows someone to be incapacitated by allergies? The answer lies within nature itself-our immune system. The Immune System Cure provides simple techniques for supercharging your immune system to resist and prevent disease. Through diet, exercise, stress reduction and nutritional supplements, including plant sterols and sterolins, you can harness the power of your immune system in just 30 days and help it combat: Antibiotic-resistant... View Details


A Guide to Transfer Factors and Immune System Health: 2nd edition, Helping the body heal itself by strengthening cell-mediated immunity
by Aaron White PhD (Author)

In the second edition of this popular book, Dr. White takes readers on a tour of the human immune system, explores the nature of immune disorders from cancer to HIV and presents evidence that immune messengers called transfer factors can help the body beat a wide variety of diseases for which effective treatments are lacking. In language that is easy to follow, Dr. White explains how transfer factors help the body fight viruses (herpes, hepatitis C, HPV, HIV), mycobacteria (tuberculosis), cell-wall deficient bacteria (Lyme), cancers, autoimmune diseases and other conditions. Like vaccines but... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Big Five
What are the five biggest global challenges we face right now — and what can we do about them? This hour, TED speakers explore some radical solutions to these enduring problems. Guests include geoengineer Tim Kruger, president of the International Rescue Committee David Miliband, political scientist Ian Bremmer, global data analyst Sarah Menker, and historian Rutger Bregman.
Now Playing: Science for the People

#457 Trowel Blazing
This week we look at some of the lesser known historical figures and current public perception of anthropology, archaeology, and other fields that end in "ology". Rebecca Wragg Sykes, an archaeologist, writer, and co-founder of the TrowelBlazers, tells us about the Raising Horizons project and how their team is trying to shine the spotlight on the forgotten historical women of archaeological, geological, and palaeontological science. And Kristina Killgrove, assistant professor of anthropology at the University of West Florida and science writer, talks about the public perception of the fields of anthropology and archeology, and how those science are represented -...