Playing the Odds

01.10.1999

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Prof. Avi Levy and Vera Gorbunova: DNA repair and evolution
 
Rapid evolution is crucial for plants, embroiled as they are in a race for survival against formidable armies of fungi and bacteria.
 
"Plants evolve far more rapidly than mammals," says Prof. Avi Levy of the Weizmann Institute's Plant Sciences Department. "In the last 300 million years, only 4,000 mammalian species have evolved, in contrast to nearly 200,000 flowering plant species exhibiting a plethora of shapes, colors, and adaptations." Plants also demonstrate much greater variation than mammals in the amount of DNA per species. This genomic plasticity may be the plant's answer to a main grievance: unlike mammals, plants cannot flee in the face of danger; they have no choice but to stand their ground.
 
Levy and doctoral student Vera Gorbunova are investigating the underlying mechanisms that enable plants to be so versatile. They have found that compared to mammals, plants are highly prone to making "mistakes" when repairing damaged DNA. According to Levy and Gorbunova, the plant's error-prone repair strategies may actually be a blessing in disguise -- driving evolution forward by enhancing genetic variability.
 
"Plants tend to 'improvise'," says Gorbunova. "While their repair mechanisms seal a tear in the DNA, as do those of mammals and yeast, plants often 'rewrite' or 'delete' parts of the DNA in the process. The 'repaired' DNA is rarely identical to the original."
 
Genetic mutations occur regularly in all organisms as a result of environmental factors, including ultraviolet radiation and chemical toxins as well as, on a smaller scale, natural cell processes. Plant mutations are also influenced by jumping genes: during cell division these natural trailblazers are capable of jumping along the plant's DNA, randomly "knocking out" genes. Collectively, these mutagenic factors leave chaos in their wake, tearing the DNA and scrambling and deleting the genetic "letters" encoding an organism's traits.
 
Damaged DNA, if not repaired, can have disastrous consequences, especially in organisms that can develop cancer as a result. In plants, mutations can accumulate without the danger of their leading to cancer, since cells do not move within the plant body.
 
Fortunately, all organisms employ emergency repair "crews" designed to reverse or mitigate mutation-induced damage. Weizmann scientists have discovered that the mutation repair systems in plants are highly error-prone. In roughly 70% of cases, plants will simply "paste" torn DNA ends together, using a biological Scotch tape repair enzyme known as DNA ligase. This unsophisticated technique does not take into account the numerous complications that can occur.
 
"Unlike a precise cut made by scissors, DNA breaks generally result in the loss of entire pieces," says Gorbunova. In addition, exposed DNA ends are immediately scouted out and attacked by degrading enzymes. Therefore, simple rejoining via ligation generally leads to scrambling of the genetic code or loss of information.
 
Most interestingly, Levy and Gorbunova found that plants even "stitch" together diverse DNA from multiple sources. An apt analogy: Faced with a disastrous tear in their favorite jeans, plants generally sew the edges together; or they go for a dramatic fashion statement, introducing a different fabric or even a multicolored patchwork. In contrast, yeast takes the conservative route, replacing the missing fabric with identical material, Levy explains. Yeast does so by going to a homologous chromosome (genetic information is usually organized in pairs, termed homologous chromosomes, with one member of each pair originating from the female parent and the other from the male). According to the Weizmann team, when DNA in yeast is damaged, missing fragments are obtained by invading the homologous "partner" and copying an identical sequence. Plants also employ this strategy. But instead of choosing the problem-free homologous repair route, they commonly invade a nonidentical chromosome, leading to the insertion of unrelated DNA sequences.
 
Plants are wonders of evolution
 
 
These new insights into mutation repair pathways may lead to breakthrough genetic engineering efforts. "Today, it is nearly impossible to target a specific gene in order to effectively integrate beneficial traits into the plant genome," says Levy. "With yeast, in contrast, the 'designer' gene inserts itself directly into a homologous target." One prevailing idea is to introduce "blinders" into DNA modification pathways by "knocking out" or inhibiting the genes involved in non-homologous repair. "In this scenario, the DNA would have to use the alternative homologous machinery - thereby enabling precise integration and effective expression of beneficial traits."
 
"This phenomenon may provide a telling example of how error-prone DNA repair can generate useful traits," says Levy. The inherent approach is to absorb the loss of "bad" mutations -- an inevitable by-product of error-prone repair, so as to receive the "good" adaptability-enhancing sequences. The overriding strategy of plants for overcoming the problem of immobility may read as follows: become "star athletes" in the evolutionary race instead.
 

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