By David N. Leff

When the Spanish conquistadors, with their missionaries, invaded Mexico half a millennium ago, they found the Aztec population eating a small, reddish fruit they called tomatl. The newcomers shipped this New World comestible back to Europe, where it eventually took root in gardens and eating habits.

Ages earlier, the peoples of Central and South America had cultivated a distant, direct ancestor of the Aztec's tomatl - a wild, red, spherical fruit the size and shape of a modern blueberry.

"Today," observed Cornell University plant geneticist Steven Tanksley, "when you see a beautiful, plump tomato, you're actually looking at a gross exaggeration of the fruit's ancestral anatomy. If not for this mechanism," he pointed out, "we humans would not have developed beyond the hunter-gatherer stage, and modern civilization would not have been born."

Tanksley is senior author of a paper in today's issue of Science, dated July 7, 2000, bearing the title: "fw2.2: A quantitative trait locus key to the evolution of tomato fruit size."

"Our purpose," Tanksley told BioWorld Today, "was to understand how plants - in this case, tomato - some time in the past 10,000 years, evolved from a wild plant bearing very small, inconspicuous berries, into these huge fruits that we use for agriculture. That progenitor of the domesticated tomato [Lycopersicon esculentum]," he noted, "most likely had fruit less than 1 centimeter in diameter and only a few grams in weight. In contrast, modern tomatoes can weigh as much as 1,000 grams, and exceed 15 cm in diameter.

"The original goal of our effort," he continued, "was to unravel how that took place - both the genetic and the molecular mechanisms. The challenge of it, which is now a common challenge across biology," Tanksley said, "is to find the individual genes underlying complex traits, which this is. That growth in size is not a simple one-gene change, and suddenly we have this big tomato. Rather, it's a quantitative trait

"What we've done over the past few years," he recounted, "was to utilize a molecular map of tomato to pinpoint the regions in its 24 chromosomes that are responsible for this transition from very small to very large. Then we genetically characterized these regions and prioritized 30 candidate genes. Starting at the top of the list, we studied those that had the largest effect, then moved down to those with overall smaller effect. Next we began to clone these chromosomal loci one by one. The Science paper," he observed, "reports our cloning the first one of those genes involved in this complex trait of fruit size."

Meet ORFX - 'Open Reading Frame' Gene

That gene, ORFX, resides on chromosomal locus fw2.2 of the tomato genome - a hot spot for the complex, quantitative trait. "The designation 'fw,'" Tanksley explained, "stands for 'fruit weight.' It's just the nomenclature for identifying the positions of all the loci responsible for the fruit-size changes. The first number 2 denotes that the locus where the gene resides is on tomato chromosome 2, while the second 2 indicates it's the second locus identified on that chromosome - conferring the change in fruit weight."

Tanksley recalled why he and his co-authors gave that first gene, ORFX, the name they did: "ORF stands for 'open reading frame,' and X is the letter we gave it. The reason why we called the locus 2.2 and the gene ORFX is that when we did the original mapping, we located a position on the chromosome that controlled the quantitative trait. We discovered that there was a single ORF in the region, which we named ORFX. This gene alone was increasing the fruit size by about 30 percent, over one generation."

The protein that the ORFX gene encodes has a function only now under study. "What we know at this point," Tanksley said, "is that the gene is a controller of cell division very early in fruit development. That is, the mutation associated with the increase in fruit size is apparently a mutation in the regulation of the gene, not in its protein sequence. So a current model is that this gene is a stop sign for cell division. Its mutation partially disrupts the ability of the tomato plant to control cell division, so it ends up much larger than is normal."

Whether there's any limit to this enlargement, Tanksley proffered, "we don't know yet, because the mutation associated with the fruit-size change doesn't totally remove the control of cell division. Otherwise the plant would have the equivalent of cancer, which means growing uncontrollably."

Computer Algorithm Bumps Into Ras Oncogene

Which leads to the co-authors' surprising discovery of the tomato/human oncogene connection: "The protein's amino-acid sequence, expressed by the ORFX gene," Tanksley recounted, "was predicted by computational data worked up here at Cornell, to have structural homologies with the human oncogene c-H-ras p21. This suggested a common mechanism in the cellular processes leading to large, edible fruit in plants - and cancer in people.

"In humans," Tanksley went on, "when you have a mutation you wind up having cancer - losing control of cell division. The counterpart in plant genes we studied is one, ORFX, which controls cell division. Its mutation doesn't cause cancer, but rather what some might consider partial tumorization - producing a much larger fruit than is found normally. It's kind of an interesting connection biologically," he reflected, "that these two processes might be related, even functionally related, through similar types of proteins."

Tanksley sees no human implications in this plant-person parallel, but he added, "Prior to this, we would never have looked toward cancer research for anything related to how plants produce edible tomatoes. But now we're on a parallel path, maybe a convergent path, because we're looking at cell-cycle control, cell division control, and possibly even a plant protein that's similar to a cancer-related protein in humans. I think," he concluded, "we are rapidly entering into a period where the discoveries that have major impact on one field of study may well come from another."

Last March, Cornell applied for a U.S. patent titled "fw2.2. Gene controlling fruit size in tomato," with Tanksley as lead inventor.

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