Are they good or are they bad? Genetic mutations, that is. The answer, like the answers to so many other questions in life is: It all depends. What it depends on is context, and that context has to do with Darwin and the ways in which cancer inhabits and inhibits the lives of our planet's beings.
It all starts with our day-to-day existence, when the DNA in living cells is exposed to a plethora of environmental effects solar rays, chemical materials, the by-products of the metabolic process within the cells themselves, etc. Simply stated: Our DNA becomes all stressed out.
These stressful influences may consequently damage DNA, and are expressed in change, breakdown, and replacement of the genetic "letters" which comprise our genetically-encoded information. (DNA is built from millions of these genetic letters.) Damaged data leads to the creation of defective proteins, which may in turn alter the correct operation of the cell. Under certain circumstances, this can even lead to cell death.
Here's the lowdown on understanding how mutation works.
"Bad" mutations may activate cancer-causing genes, or "switch off" cancer-resistant genes; without the protection of resistance, there's a possibility of the development of cancerous growth. Other negative mutations are liable to jumpstart the processes which cause the appearance of other diseases.
On the other hand, "good" mutations form the steps upon which life ascends the evolutionary ladder. In fact, without mutation, evolution is impossible.
We're all familiar with that first evolutionary revolutionary, Darwin. While he didn't have access to the sophisticated research techniques of today, Darwin's work constituted a precursor to the field of genetics.
A century later, scientific research is delving into the wide genetic differences by which natural selection acts. Darwin certainly would have been intrigued to learn that selection is based on the accumulation of nonfatal mutations in hereditary DNA material within the nuclei of all living creatures. This process sometimes triggers an improvement in the survivability of living creatures.
That's where Prof. Zvi Livneh and his research students, Nina Reuven and Guy Tomer, of the Institute's Biological Chemistry Department, come into the evolutionary picture. With survivability the issue, the Weizmann Institute team is asking this question: How do you prevent and reduce, to whatever extent possible, the damage of the bad mutations on one hand, while on the other, preserve what is most beneficial about the evolutionary process?
What we do know is that the living, breathing world has its own built-in, sophisticated mechanisms that allow cells to repair defective DNA. However, these mechanisms aren't always perfect; they sometimes undertake their work with a certain degree of "negligence." This opens the possibility for other mutations, only some of which may be considered beneficial ones.
Mutations are incorrect coding instructions, formed when the replication machinery duplicates the DNA regions containing the unrepaired lesions. It was originally thought that replication stops when encountering damaged DNA, and that the process would continue only with the assistance of "helping proteins."
What Livneh and his team discovered is that the enzyme polymerase, which replicates the DNA, "didn't stop at the red light" when it came upon the damage not even in the absence of the helping proteins.
So why are the helping proteins required at all?
First, the helpers make the replication of DNA damage go faster. But what Livneh and team found is yet another reason: The choice of the polymerase to replicate the damaged region either by itself, or with the assistance of the helping proteins, is a life or death decision.
Without the presence of helping proteins, the polymerase ignores DNA damage, leaving blank spaces of one or two letters in the DNA's genetic continuity. If DNA is like a book containing words made of letters that appear in triplet form, removing one or two of them sends a whole different message. For example, if you have the sentence "Dad did cry" and you remove "D" from "Dad," the message is read as "add idc ry." The message is clearly set askew.
This leads to the creation of shortened proteins that are liable to hasten the cell's death. When polymerase encounters damage and continues its action in the presence of helping proteins, it fills in the blanks created in the genetic continuity with random genetic letters. While this still leads to the creation of a mutation, it is a mild type and the mutant proteins can work, if only partially. In any event, they do not usually bring about the death of the cell. In fact, they may act like some of us do when we're under stress: We perform better. On occasion, the mutation can actually improve the protein.
Livneh: "We knew this before, but we didn't know the rationale for it. If the helping proteins aren't there, the replication machine is making disastrous mistakes."
Prof. Livneh's discovery: reconstituting the entire mutagenic process in a test tube by taking components from billions of living cells. Put them to work outside the cells.
Sit back a few minutes while the entire filling-in process happens in a matter of minutes.
What does Livneh's research have to do with life in the 21st century? Plenty. It's important to note that one way bacteria acquire resistance to antibiotics is due to mutation. Beneficially, one of the potential, long-range applications of Livneh's work is the possibility that some day, we may be able to counteract this scary news: We're running out of antibiotics that kill bacteria.
Under most circumstances, it is clear that mutations created as a reaction to conditions of stress, improve the ability of bacteria to survive these conditions. Prof. Livneh's research is likely to broaden the boundaries of our knowledge regarding the ways in which living creatures are able to adapt to environmental conditions through evolution, good or bad.
It all depends.
.jpg "Normal mouse cells (l) and cells in which the MTCH2 gene is knocked out (r), after exposure to a cell suicide factor. Arrows point to a protein that initiates the cell suicide program, which is only released from mitochondria with functioning MTCH2")
.jpg "(l-r) Liat Shachnai, Natalie Yivgi-Ohana, Prof. Atan Gross, Maria Maryanovich and Dr. Yehudit Zaltsman-Amir")
 Tokurik.jpg "Tokuriki. Not disappointed in the experience")
Engineered Enzyme Protects against Nerve Gas
A multidisciplinary team of scientists at the Weizmann Institute of Science succeeded in developing an enzyme that efficiently breaks down certain forms of nerve gas before damage to nerves and muscles can ensue. Their results were published in Nature Chemical Biology.
Prof. Dan Tawfik of the Weizmann Institute’s Biological Chemistry Department and his group developed a special method to induce “natural selection” of enzymes in a test tube, enabling them to engineer tailor-made enzymes. Tawfik showed that this method can improve the efficiency of enzymes by factors of hundreds and even thousands.
Prof. Joel Sussman's research is supported by the Jean and Jula Goldwurm Memorial Foundation; the S. & J. Lurje Memorial Foundation; the Nalvyco Trust; Mr. Harold Chefitz, Livingston, NJ; Mr. and Mrs. Yossie Hollander, Israel; Nicolas and Elsa Neuman, Mexico; Dr. Ze'ev Rav-Noy, Los Angeles, CA; the Bruce and Rosalie N. Rosen Family Foundation; and Harry Sussman, Woodbury, NY. Prof. Joel Sussman is the incumbent of the Morton and Gladys Pickman Professorial Chair in Structural Biology.