Was genetic code an accident?
Biologist seeks to "turn deep philosophical questions into testable hypotheses"
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Laura Landweber (Photo by Denise Applewhite) |
When Princeton scientists announced last month that they had created a kind of computer from RNA, the idea had the ring of something radically new.
Here was a test tube full of the squiggly little molecules that put our genes into action, and it was able to solve a complicated chess problem.
But, as project leader Laura Landweber points out, she was just taking a cue from something nature already accomplished billions of years ago.
Landweber, assistant professor of ecology and evolutionary biology, studies the origin and evolution of biological information. When life emerged on the newly formed Earth 3.8 billion years ago, one of the first things that developed was a system for encoding information in biological molecules--what we now know as RNA and DNA. For Landweber, making a computer out of RNA was a similar challenge: How do you encode information into a molecule and then manipulate it to solve problems?
Trillions of calculations
Her answer to the question appears in the February 15 issue of the Proceedings of the National Academy of Sciences. The finding represents a significant advance in the emerging field of biological computing, which may offer a way to solve some complex problems more efficiently than conventional computers can do.
This test-tube computer does not have any immediate applications, and it will probably never completely replace silicon technology, but it does have attractive aspects, says Landweber, who collaborated on the project with professor of computer science Richard Lipton, postdoctoral fellow Dirk Faulhammer and Anthony Cukras '98.
One advantage is that the genetic molecules DNA and RNA, which encode all the instructions for creating and running life, can store much more data in a given space than conventional memory chips. Another benefit is that, with vast numbers of genetic fragments floating in a test tube, a biomolecular computer could perform millions or trillions of calculations at the same time.
"It begs the question, What is a computer?" said Landweber. "A computer can be an abacus, it can be many types of devices. This is really an abstraction of a computer."
One-celled computer wizards
Many aspects of life can be seen as abstract forms of computing. In another area of research, Landweber has studied single-celled organisms (ciliates, slime molds and trypanosomes) that continually rearrange their genetic material in ways that demand sophisticated problemsolving. These organisms have genes that appear to be encrypted; in order to read the information on a gene, the cell first has to collect all the parts and stitch them together in the right sequence, through processes called gene unscrambling or RNA editing.
Investigating how these processes take place, Landweber has found that the cells can produce the right solution from among thousands of alternatives, which could be a troublesome problem even for modern computers. (By contrast, the chess problem Landweber's RNA computer solved had 512 possible answers.)
Some of the organisms Landweber has studied cause the tropical illnesses Chagas disease and sleeping sickness. Understanding how these parasites accomplish their gene editing may offer insights into treatments, she notes.
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In the smaller nucleus (below), genes are scrambled, with sections dispersed across long chromosomes. In the larger nucleus, these scrambled
segments are assembled into working genes.
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Observing such unusual systems may also yield insights into more fundamental questions about why most living things have the genetic code we almost all seem to share. A significant part of research in the Landweber lab consists of theoretical, even philosophical investigations into the origin of life.
For a long time, says Landweber, studying the origin of life has been "a very philosophical and speculative discipline. It has only recently begun to yield to experimentation." A principal question in her lab is, How did our system for encoding information in genes come to be? And why does it have the structure it does?
For more than 30 years, the leading hypothesis has been that our genetic code is a "frozen accident" -- that is, the system for encoding information in genes randomly fell into place in some primordial organism and was then perpetuated throughout evolution. Landweber and colleagues in her lab have produced important results refuting that hypothesis and suggesting many properties that influenced how the genetic code evolved to its current state from less sophisticated precursors.
For example, using computer models of the evolutionary process, potdoctoral fellow Stephen Freeland showed that our genetic code is nearly optimal in terms of protecting against errors. Such good design, argues Landweber, suggests the code is not an accident.
Another piece of evidence came from graduate student Robert Knight, who developed a quantitative test that revealed purely chemical reasons why the code is not likely to be an accident. Knight and Landweber found that RNA, a molecule that contains instructions for making proteins, often has a chemical affinity for the amino acids it describes. It is like finding an association between the words on a page and the objects they denote, as is the case with, say, hieroglyphics. The association is much too strong for coincidence, says Landweber.
Organizing principles
If it's not an accident, then perhaps there are some organizing principles that led to the creation of life. "This suggests there are some fundamental laws underlying at least the establishment of the genetic code, and we're getting closer to understanding them," says Landweber.
In each of her areas of research, Landweber says, the challenge is to "turn deep philosophical questions into chemically or computationally testable hypotheses."
Martin Nowak, a theoretical biologist at the Institute for Advanced Study, says that is something Landweber is particularly good at. "Laura is on top of her field because she's able to combine experimental with theoretical work, and that is very rare in biology," says Nowak. "I find her work extremely interesting."
Landweber has been interested in the evolution of genes and biological molecules since high school. Growing up in West Windsor and attending public school there, she read articles by such evolutionary biologists as Stephen Jay Gould and Allan Wilson and was inspired to investigate the forces of evolution at the molecular level.
Attending Princeton with the Class of 1989, she majored in molecular biology. She received her PhD in biology from Harvard in 1993 and then was a junior fellow in the Society of Fellows before returning to Princeton as an assistant professor in 1994.
"It's nice to come back to a department where I felt so welcome as an undergraduate," Landweber says. "Nice but I admit at first a bit daunting."
She has found a place as a liaison between the departments of Molecular Biology, and Ecology and Evolutionary Biology. Students from both departments have sought positions in her lab, and she says it has been gratifying to see how well different members of the lab have worked together.
"It's just the kind of synergy that you hope to see in a lab. That's one of the best parts about running a lab: sparking good interactions and collaborations within it."
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