The Principle of Pairs 1: Toward a Plant Genome Initiative that is both socially and intellectually vibrant.
(dateline 10/97 and still valid)
It is exciting to think that a US Plant Genome Initiative could receive funding and guidance from our government. Deep EST mapping and "gene machines" for corn and rice are obviously crucial. Sequencing a rice genome, or perhaps its distal chromosomal arms, is essential to provide an anchor for the grasses and monocots; Arabidopsis alone is not adequate. Also obvious is to relate information in the anchor grass genomes to other commodity grasses, all of which are not only microsyntenous, but are largely macrosyntenous as well, as if large arm-sized chunks of genome have mostly stayed together for the last 80 million years.
The following position document hopes to establish another goal of a Plant Genome Initiative that I feel is very important, and may not be so obvious. This argument I call "The Principle of Pairs." It provides a way that US investment in plant genomics can be seen as both advancing the knowledge and economy of the developed world, but also identifies the unfathomable value of the rich biodiversity and novel genes held largely in the exotic plants growing in relatively money-poor parts of the world.
At the present time, EST maps of all 9 crop grasses mapped show enough macrosynteny to permit aligning all of them using one circular diagram; this "circle of grass" can be seen 2 in either the literature or at a convenient website. There are at least 10,000 grass species, and many pairs of species that are closely related, but differ dramatically in a particular morphological or physiological characteristic.
Among thousands of examples, salt-tolerance is one interesting character. If a cross could be made between a tolerant and intolerant species, then the hybrid could be backcrossed to the "simpler" (recessive) parent. The progeny would be expected to segregate for the character, or some component of the character. Where there is segregation, then there will be linkage to one or more pan-grass EST, perhaps using AFLP technology for efficiency. That is, there will be linkage via macrosynteny to a location corresponding to a spoke that might be drawn on the circle diagram. Once some linkage is found, closer linkages can be found. In this simple, Mendelian fashion, some component (a QTL) of the character, salt-tolerance, could be placed onto a rice bacterial artificial chromosome-cloned piece of DNA. At this point, the candidate DNA pieces might be cloned from the salt-tolerant exotic and transferred, using transgenic technologies, into a crop where the engineered plants might be assayed for both salt tolerance and loss of yield.
It is heartening that wider and wider crosses are now being performed within the grasses, that pairing seems not to be impeded by massive DNA-content differences, and that transgenic technologies are improving rapidly. In this way, using the "Principle of Pairs," genetic resources evolved within exotic food relatives might be brought into the service of humans, as might well prove to be essential in order to continue living on our degraded planet after we finally reach ZPG. In other words, I think that, ultimately, the value of the Plant Genome Initiative will not be that big-brained genetic engineers will know enough to design better commodities. Rather, I think the real value is that we will be able to garner exotic, useful genes from the wild, genes already engineered by natural selection.
There is no way to save every valuable plant species from the extinctions predicted in the decades ahead. If we can reasonably predict that any germplasm that is particularly valuable via "The Principle of Pairs" and the Plant Genome Initiative is facing extinction, then this taxon-- say a tribe of a grass genus in tropical Africa that includes species that accumulate a valuable metabolite-- might be placed higher in a science-based priority for preservation.
There is a social implication to the "Principle of Pairs." The expertise needed to act on this principle exists already, among systematists, environmental biologists, preservationists, conservationists and horticulturists who, in rich and money-poor countries alike, often feel at the margin of what might be called "cutting edge research." I feel that a Plant Genome Initiative with vision will not focus only on technological objectives, but on biological objectives as well.
It is pleasant to note that this biological research aim, while demanding in terms of expertise and manpower, is neither technical nor intellectually boring (unlike most of genome research), and is perfectly suited to smaller laboratories and field operations situated all over the world. According to the UN Biodiversity Convention, valuable exotic germplasm belongs to the country of origin. 15% of the total Plant Genome Initiative budget should be set aside for this multinational program to discover new, valuable genes.
If my advice is taken, the Plant Genome Initiative could happen within an intellectually and socially vibrant program, and would also be a lot more appealing to the general public than a program largely justified on its ability to bolster the US economy by improving chicken and pig feed.
Michael Freeling
1 This phrase emerged in a discussion between the author and Professor Elizabeth Kellogg, a systematist and geneticist at Harvard, January, 1997. Although the phrase is new, there is a compelling literature that supports the feasibility of this principle.
2 From Moore, et al., 1995. Grasses, line up and form a circle. Curr. Biol. 5: 737-739. Visit http://www-iggi.bio.purdue.edu, and especially /cartinhour.html. Review: Bennetzen, J.L. and M. Freeling, 1997. The unified grass genome: Synergy in synteny. Genome Research 7, 301-306.