James A. Shapiro: Experimental Evolution II: More Ways to Watch Natural Genetic Engineering in Real Time

Posted: July 2, 2012 at 11:24 pm

In February last year, The New York Times published an interview with my University of Chicago colleague Janet Rowley. Janet is deservedly famous for finding a repeated chromosome rearrangement in certain types of leukemia. This was one of the earliest indications that genome changes in cancer cells do not occur randomly.

In the interview, Janet explained how she discovered this particular chromosome change, now called the "Philadelphia Chromosome." She was just looking through the microscope, motivated by her curiosity to know more about these tumor cells.

Janet pointed out that she might well not be able to repeat her discovery in today's scientific environment. She was practicing what she called "observationally driven research." Today, she said, granting agencies don't support that kind of work. "That's the kiss of death if you're looking for funding today. We're so fixated now on hypothesis-driven research that if you do what I did, it would be called a 'fishing expedition,' a bad thing."

In other words, you have to know what kind of result to expect before the funding agencies will give you money to look for it. Surprises are not fundable. But "surprise" is just another word for "discovery." As Janet put it, "I keep saying that fishing is good. You're fishing because you want to know what's there."

Let's look at how we would "fish" for complex genomic novelty through natural genetic engineering. I can think of two approaches. There will definitely turn out to be more.

One approach was included in my book. The idea was to do interspecific hybridization with a well-characterized organism, like the mustard weed Arabidopsis, and follow what happens with the genetically unstable hybrid progeny.

We know that interspecific hybridization and genome duplication lead to high levels of genomic and phenotypic variation. DNA sequencing has found evidence of genome duplication at many critical points of evolutionary divergence, especially in plants. There is a fine Scientific American article by the famous 20th-century evolutionist G. Ledyard Stebbins entitled "Cataclysmic Evolution," which describes how hybridization between two wild grasses can recreate the origin of flour wheat.

The hybrid progeny can be followed, and those plants that develop significant new traits, such as flower patterns, can then be analyzed. Sequencing the whole Arabidopsis genome in a short time is now feasible. The sequence data will let the Arabidopsis genome speak for itself in telling us how the new traits evolved.

We can then look for multiple changes that show signs of coordination in the underlying natural genetic engineering events. Such coordinated events might be insertions of the same or related mobile elements at distinct locations in the genome or the addition of the same domains to more than one protein in the network responsible for development of the novel trait.

The second "fishing" approach to asking how a novel feature can evolve would use a microbe, as suggested in the previous blog on experimental evolution. In this case, however, the changes would not be pre-targeted to a number of different sites in the genome.

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James A. Shapiro: Experimental Evolution II: More Ways to Watch Natural Genetic Engineering in Real Time

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