Significance of AGI and life after

THE UNFANCIED weed opens up beneficial applications ranging from crop improvement, increased food production, improved nutrition to development of new drugs.

The first complete genetic sequence of a flowering plant, Arabidopsis thaliana, has been determined.

Arabidopsis, an ungainly weed albeit a close cousin of the mustard has now joined elite ranks among the motley cluster of the fruit fly Drosophila melanogaster,a soil nematode Caenohabditis elegans and a fungus, the ubiquitous yeast Saccharomyces cerevisiae whose genome has been researched upon, sequenced.

The completion of the Arabidopsis genome study(AG1) is the culmination of a remarkable decade of trans-continental collaborative research spanning the U.S, Europe and Japan in understanding this species as a model genetic and genomic system.

The fancy for this weed as a research tool dates back to the decade of 1930's when plant geneticists took a liking to it for its short generation cycle, disposition to self- pollinate and ability to produce numerous tiny seeds, each being an event of a myriad of meiotic recombinations.

Work in the mid 70's and early 80's from the laboratories of Elliot Meyerowitz, Maarten Koorneef and David Meinke determined the weed to have a small and compact genome comprising 5 sets of chromosomes and recognised an opportunity for the early studies in genetics through deletion mutants.

Significantly, however, this plant was not the chosen favourite of eminent scientists of the day who discounted the possibility of a 'model plant system' arguing instead the diversity of crop plants and the funding pattern in vogue in the US then that supported plant-related research promoted insightful investigations into agronomically important species!

Indeed an activist group of Arabidopsis converts recognised the scientific validity in pursuing these studies and foresaw significant gains in knowledge that bore a relevance to the whole gamut of biology cutting across species barriers.

The Multinational Co-ordinated Arabidopsis Genome Research Project and the North American Arabidopsis Steering Committee came about. Several significant developments concomitantly helped along.

Early on, Monsanto determined a rough sequence of a strain of this species but came up with about 40,000 differences between its sequence and the one that emerged from the public domain.

To the credit of Monsanto, it must be applauded for making public its research findings, which hastened the finalisation of the final sequence.

The result, within ten years of its initiation, the complete sequence of Arabidopsis genome is at hand. Made up of five pairs of chromosomes, the genome consists of 115,409,949 base pairs (bp) represented by the letters A, G, C and T, which is significantly smaller than the human genome whose working draft published a month ago talks of a 3.1 billion base pairs representing 23 pairs of chromosomes. There are 25,498 genes. A total of 11,601 protein types have been identified.

On a comparative note, C. elegans has 19,099 genes while D. melanogasterhas 13,601 genes. Whereas Arabidopsis and C. elegans have a similar gene density, Drosophila has a lower gene density.

Arabidopsis further has a significantly greater extent of tandem gene duplications and segmental duplications, which together are postulated to account for its larger gene set.

Interestingly, most functions identified by protein domains are fairly conserved in all the four genomes elucidated so far, which signify the ubiquitous nature of eukaryotic pathways.

This is illustrated from the fact that at least 17 human disease genes ranging from Hyper-insularism to Heredity Deafness, Fam Cardiac Myopathy, Myotonic Dystrophy have high levels of similarity to this weed's genes.

The Significance: The elucidation of the genome of a complete flowering plant, Arabidopsis thaliana provides insights into the genetic basis of the similarities and differences of diverse multicellular organisms.

It further facilitates direct and efficient access to a much deeper understanding of organismal development and its responses to the environment, allowing for a better assessment and understanding of structure and dynamics of genomes.

Arabidopsis, C. elegans and Drosophila each have a similar range of 11,000 to 15,000 different types of proteins, suggesting this to be the minimal level of complexity enjoined by diverse multicellular eukaryotes to carry out their development and to counteract with their environment.

Importantly, Arabidopsis is the first methylated eukaryotic genome to be sequenced, which would provide invaluable insight into studies of epigenetic inheritance and gene regulation in the future.

As compared to most animals, plants generally do not move, spend a significant portion of their life cycle in haploid phase, can perpetuate indefinitely and importantly synthesise all their metabolites.

The Arabidopsis genome helps our understanding of these fundamental differences between plant and animal kingdoms. Basic intracellular processes such as translation and vesicle trafficking appear to be conserved, reflecting a common eukaryotic ancestry. However, more elaborate intercellular processes proceed along different pathways.

Notably, membrane channels, transporters and signalling components are distinctly different among plants and animals. Interestingly too, apoptosis and absence of intracellular regulators of cell division, both anticipated to bear high levels of genomic similarity in the two groups due to high similarity of these processes, are different. Yet, DNA repair mechanism is more closely conserved between the two groups.

The Road Ahead: The advent of the Arabidopsis genome and the new understanding it engenders to genetic mechanisms at the molecular and cellular level rings in newer insights to understanding of the organism. Genetics of the future is rendered easy because of the molecular assays of mutations now possible.

Consequently, determination of the function of a large number of predicted genes exploiting site-selected mutagenesis is in the offing in the days ahead. Detlef Weigel of the Salk Institute has set the tone to the gains to be had by transferring the Arabidopsis gene into the Aspen tree thereby triggering it to flower in a few months as compared to the 8 to 20 years it took in its native state.

With this rolls in potential gains in understanding and exploiting beneficial genes and the useful traits they code for, towards crop improvement and sustaining global food security through the intervention of transgenic crops.

The knowledge gained from this major endeavour will ultimately define the basic building blocks of this model plant and provide the tools for manipulating desired traits in other more complex organisms including that of creating novel drug designs and more efficient drug delivery with less or no side effects. The U.S, National Science Foundation has initiated a 10-year programme to determine the functions of all the genes and how they function together.

The ultimate goal is to create a 'virtual plant' whose form and function helps model the performance and responses of a given plant type in a given environment that can be gleaned at the touch of a button. The brave new world is nearer at hand!

Gurumurti Natarajan

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