New Evidence for the RNA World

Every instructor of an introductory biology class is faced with a dilema to present to their class. While we know that DNA is the genetic material of all living organisms (except some viruses - but most do not consider them as "living"), it appears to have been absent from the early Earth. So what was the original genetic material? And, more importantly, do we have any evidence to support this hypothesis?

Before we look at the alternatives, was wasn't DNA the original genetic material on the planet? One main reason, of course, is its complexity, and the fact that DNA requires a host of proteins and enzymes to assemble and copy itself. These enzymes are encoded within the DNA, so that leaves us with a "chicken and egg" scenario. The DNA molecule itself lacks any catalytic abilities - meaning that it does not conduct any chemical reactions. It is like the hard-drive of your computer - pretty much useless without a host of assistants to get the information in and out.

For some time scientists have recognized that a second form of nucleic acid, RNA, is the solution to these problems. RNA is a much simpler molecule. It is usually short and only consists of a single-strand of nucleotides. More importantly, RNA molecules can themselves act an enzymes. This type of RNA is called a ribozyme, and its activity appears to solve many of hurdles faced by the early genetic material. The fact that RNA may have been the earliest form of genetic material is called the RNA world hypothesis.

There has been only been one real problem with the RNA world hypothesis. How did the individual components, called nucleotides, of the RNA molecule self-assemble. Many explanations have been proposed, but finally, due to the activities of a group of researchers at the University of Manchester, we are one step closer to understanding. Dr John Sutherland, a chemist has demonstrated a series of chemcial reactions that can occur naturally to form the nucleotides of RNA. This could be a very important advance in the life sciences - previously we have known how to form the nucleotides synthetically (i.e, in a lab), but not under natural conditions.

Now here is where we can link astrobiology (also called exobiology) and genetics together. We are currently exploring Mars for life, and will soon we taking a good look at both Europa and Titan (moons of Jupiter and Saturn, respectively). While it is useful to look for life as we know it - what would be more interesting would be to tart to look for proto-life, molecules that are self-assembling and replicating. Using Sutherland's data, we should be taking a good look at these locations of evidence of RNA-building blocks. By doing so we can understand more about how life first evolved on our planet.



For more on Sutherland's discoveries - see the NY Times article by Nicolas Wade - "Chemist Shows How RNA Can Be The Starting Point for Life"

Synthetic Biology 2.0

While the scientific community, and most of the intelligent world, has widely accepted that the theory of natural selection is underlying mechanism of organic evolution, until recently our studies of evolutionary processes have been confined to the examples from a small plant orbiting an insignificant star in a mid-sized galaxy. From this limited viewpoint we know that evolution is intimately connected with life... but as scientists, we would love to expand the reaches of our database.

The study of synthetic biology was until recently a theoretical science. Engineers, biochemists, and geneticists proposed mechanisms by which molecules and cells could evolve the basic characteristics of life through pathways other than those found on Earth. However, in recent the study of synthetic biology has progressed from a theoretical to an applied science. For example, we already know that it is possible to change the structure of the genetic code in the laboratory (see "Synthetic Life Makes Synthetic Proteins"). Now, researchers at the Scripps Research Institute have demonstrated that RNA molecules can evolve the ability to increase replication efficiency in the lab (see "Artificial Molecules Evolve in the Lab"). Each of these steps brings us one step closer to truly understanding life.

There is little doubt that the work of the researchers at the Scripps Research Institute demonstrates an evolutionary process. However, some will still argue that this is just another lab-based example of evolution, and that we don't really know for sure that the system demonstrated in the lab would work in the "natural" environment. The true test of whether synthetic biology is a viable demonstration of natural selection will only come when we finally get a glimpse of proto-life on other planets and moons. Europa, Titan, maybe even Mars, may hold "snapshots" of how early chemical evolution occurred. For too long biologists have focused simply on life on this planet. If we truly want to understand evolution and life, we need to start expanding our horizons.

Book Review: What is Life?

Anyone who has taken introductory biology is familiar with the stories of Mendel, the discovery of DNA, and Charles Darwin's adventures with evolution and natural selection. What most of these people probably do not realize is why this material is relevant in the modern age of molecular biology.


Ed Regis's book What is Life? Investigating the Nature of Life in the Age of Synthetic Biology takes the reader on the journey from the 1943, and the publication of Erin Schrodinger's What is Life? to the labs of modern day biochemists, cell biologists, and geneticists, who are beginning to unravel some of the fundamental questions about life. The book explores how we, as scientists, have reached the ability to develop life in the lab. This is often called synthetic biology, and it is frequently thought of as being the stuff of science fiction. Several of my blogs have covered topics relating to synthetic life (for example, see Synthetic Life Makes Synthetic Proteins), most because this is going to be a hot topic for society in the next few years. For as Ed Regis points out in his book, the work is already underway, and scientists are getting closer to unlocking some of the secrets of what it means to be "alive".

For those students who are burdened with a heavy reading load, or those non-students with hectic lives, this book is a mere 171 pages in length. Better yet, it is written in a non-technical style that brings to life many of the historical people in the study of the life sciences. It is an easy read, and anyone who has an interest in understanding science should check out this book.

The Battle Against Viruses Heats Up

Viruses are nasty opponents, as anyone who has followed the battles against influenza, SARs and HIV/AIDS can attest. They are diverse and in many cases evolve at rates that confound efforts to contain them. Anyone who has gotten a flu shot, and then came down with the flu a few months later because the “strain” of virus that the vaccine was not the same as the “strain” that they were infected with, knows just how fast viruses can evolve. In many cases, medical professional never really know which virus has caused the symptoms in their patients, and this complicates treatment and often leads to the misuse of antibiotics, which, of course, are never effective against viruses.

At the ScienceWriters 2008 New Horizons in Science meeting at Stanford University (sponsored by CASW) this week, Dr. Joseph DeRisi of UCSF presented an interesting talk on his research to develop a new form of “chip” as a diagnostic tool for identifying the viral contributions to diseases. Gene chips are often used by molecular biologists to determine the relationship between a gene and an observed condition. Dr DeRisi's work takes this approach one step further.

What is interesting here is Dr. DeRisi’s application of evolutionary genomics to his work. Like microbiologists, virologists recognize that they have only identified a small fraction of the diversity of viruses that are out there in the natural world. Despite advances in sequencing technology, the ability to sequence every virus in a given environment, such as a fecal or nasal sample, is still not cost effective. However, what Dr DeRisi has done is to develop a “viral chip” that contains not the entire sequences of every virus, but rather the sequences of key genes that are evolutionarily important to certain families of viruses. When one of these viral chips is exposed to a sample, a computer program determines the level of similarity between the DNA (or RNA) in a virus and the sequence on the chip. For previously unknown viruses, this can allow a quick classification of the virus to a certain group, and has been proven to be very successful by Dr. DeRisi’s team in diagnosing diseases for which no known cause could be determined by diagnostic tools.

Furthermore, Dr DeRisi has proposed making these chips available at cost to the medical community through a non-profit organization. The availability of a new technology at an inexpensive cost would represent an important new development in the war against viruses, and would rapidly generate an increase in data for public health officials.

Additional Links

DeRisi Lab at UCSF

Good News, and Old News, about HIV

There were several important announcements in the HIV/AIDS battle this week. First was the awarding of the Nobel Prize in physiology or medicine to two French virologists,Françoise Barré-Sinoussi and Luc Montagnier, for discovering that the HIV virus causes AIDS. The side story here is the controversy that the American scientist Robert Gallo is credited by some as being the "first" to discover the virus. "First" is very important to scientists, therefore, there have been some pretty heated exchanges between Montagnier and Gallo in the past. If you are interested in some good drama, there are some decent books out there on the subject, including opposing views written by both Gallo and Montagnier.




The Nobel committee has attempted to end the dispute by announcing that Montagnier was the discoverer, a fact that is widely accepted by the scientific community, but given that there is no love lost between the Americans and the French, it is doubtful that this will die down soon.

The second announcement was that the HIV virus is probably much older than we originally thought. A discovery at the University of Arizona by Dr. Michael Worobey backs the date that the virus jumped from chimps to humans sometime around 1900 - at least 30 years earlier than originally thought.

This should not be treated as some sort of background story. In fact, it is probably the most important, and under-reported, story of the week. If you take a look at the map from the CDC below, you can see that the AIDS pandemic is showing no signs of abating.



By understanding when the virus actually made the jump from chimps to humans, we can get a better grasp on its rate of evolution. One of the biggest obstacles to the development of effective HIV vaccines has been the rapid mutation rate of the virus. As a virus mutates, it evolves, or changes, its associated proteins. Vaccines frequently target the unique proteins on the surface of a virus. Without an understanding of how this virus is continuing to evolve, the development of a vaccine could actually create more harm than good, since vaccinated people may feel that they are "safe" and can return to unsafe sexual practices and other risky behaviors. Worobey's work should provide some important insight into how HIV evolves. We should be seeing some interesting developments in the near future stemming from this discovery.

Synthetic Life Makes Synthetic Proteins

The genetic code is the metabolic instructions by which the genetic information in the DNA is translated into a protein. The fact that almost all organisms use the same code is prime evidence that all life is related in its evolutionary past. The code is considered to be "conserved" and "universal". Of course, the concept of universality may be challenged by exobiology's explorations of Mars, Europa, and Titan, but the conservative nature of the genetic code, with the exception of a few Archaebacteria, has always been a cornerstone of biological science.


But the reality of course is that the Genetic Code is like the Cobal language of computer science. The Genetic Code is old (over 3.5 billion years). Of course life on this planet is not going to update the genetic code anytime soon - it is thriving using the old code, but evolution is a weird thing, if something better comes along, and a mechanism to adapt to that change exists, the out with the old and in with the new. Until recently it appeared to be metabolically impossible to "update" the code. But one species, Homo sapiens, may have discovered a way to fast-track the process.

The basic tenants of the genetic code is that the information coming from the DNA, in the form of messenger RNA, is "read" by a ribosome three units (also called a codon) at a time. Each codon codes for an amino acid, the building blocks of a protein. Proteins are the workhorses of the cell - everything depends on them. In other words, genes code for proteins. While we have had the ability to change genes for some time, using recombinant DNA technology and genetic engineering, until recently we were always confined to the use of the same old programming language.

Earlier this year, independent teams of researchers at Harvard University and the University of Cambridge have found ways to alter not only the genetic code, but also the cellular machinery responsible for deciphering the code - the ribosome. (see Synthetic biology: Rewriting the code for life by Linda Geddes, 2008). This process is called synthetic biology, and due to the efforts of biotech giants such as Craig Venter, this is no longer science fiction. We now have at our fingertips the technology to create new forms of life that are designed for specific missions and environments.

These advances open up unbelievable possibilities, and the potential for unimaginable nightmares. It may soon be possible to manufacture proteins that were not possible from a biochemical perspective just a few years ago. This could create new drugs that could finally eradicate some of our specie's biggest problems, such as cancer and HIV. It could also allow us to develop plants that tolerate salt water, or grow on toxic waste. A new programming language means endless possibilities. It also could spell our demise as a species. After all, the evolutionary history of life on this planet tells us that if something better comes along, the old is replaced... even if it is us. Let us not be so egocentric to think that we are special from an evolutionary perspective. Unless of course, you believe that our purpose on Earth is to generate our own successors.