Introns: the war of hypotheses

biologists were taken aback by the discovery in 1977 that genes came in bits and pieces. It was found that in practically every higher organism, a dna sequence that constituted a gene was made up of two sub-units: exons (working parts of a gene that encoded a protein) and introns (intervening portions that separated exons).

Exons were spliced together to generate functional messages after the introns -- made up of non-coding dna -- were removed. What was unknown was why were introns there at all -- since they appeared to be dispensable -- and where did they come from.

These questions spawned two classes of answers. The first, called the 'introns-early' point-of-view, held that our primordial ancestors had genetic material made of small segments of dna (each capable of encoding 15-20 amino acids) separated by spacer regions. The larger genes of today are derived from combinatorial arrangements of the primordial genes. The combinations could be tried out because two small genes could yield a single functional product if the spacer was eliminated. Those hypothetical small genes came to be identified with exons and the spacers with introns. The introns-early hypothesis also posits major intron loss in many lineages.

In contrast to the introns-early theory there is the 'introns-late' theory which says that introns are relics of parasitic dna molecules that have inserted themselves into functional genes and have managed to survive by splicing themselves out, when not doing so would compromise the survival of the host and themselves. Basically, the introns-late point of view is that like a sensible parasite should, introns have entered into a working relationship with their hosts.

The two rival theories are difficult to test because they deal with what might have happened in the past. One has to take recourse to indirect methods of assessment. A possible way could be to examine whether introns do break up proteins into portions that correspond to functional sub-units. Alternatively, a second approach could be to compare patterns of intron distribution within the same gene, but in different organisms with widely varying levels of complexity. The reasoning is simple. If introns were there from the beginning, one would expect to find a relatively higher degree of concordance between the positions of introns in organisms that diverged long ago and those that diverged recently. Thus, if an intron in the same gene was present in the same location in the dna of two different organisms, the inference would be that it was also there in their common ancestor.

Researchers from two different groups -- Jan Kwiatowski and colleagues of Warsaw University (Poland) along with researchers from the University of California, Irvine ( us ), and Jeffrey Palmer and colleagues at Indiana University in the us and Queen's University in Ontario (Canada) -- have attempted just such a comparative test by looking at introns in a gene that codes for an enzyme known as triose phosphate isomerase or tpi ( Proceedings of the us National Academy of Sciences , Vol 92, 1995).

tpi , found in virtually every higher organism, catalyses the isomerisation of glyceraldehyde 3-phosphate, an intermediate metabolite formed during glycolysis, to dihidroxyacetone phosphate, which lies outside the glycolytic pathway. Both groups claim that the evidence goes against the introns-early theory.

Kwiatowski et al have found that a particular intron ('number 5') found in Culex mosquitoes is also found in Aedes mosquitoes but not in the Anopheles, nor in a fly or a moth. The intron is absent in 19 species of diverse organisms. The researchers concluded that the simplest explanation of its presence in Culex and Aedes is that it was inserted recently in a common ancestor of the two species.

The Palmer group took a differnt approach. It sequenced tpi genes from a fungus, a nematode and an insect and discovered that there were introns to be found in seven novel locations which seemed to disrupt what had been previously postulated to be functional sub-units of protein structure. Also, the team pointed out that of 21 tpi introns currently known, 12 appeared to be of recent origin, present in just one species. Once again, the implication drawn is that these results render the introns-early theory untenable.

However, notwithstanding the commendable attempts of both the groups, their observations can in no sense be taken to falsify the introns-early theory. That is because when it comes to what actually happened rather than what may have happened, results from tests on living organisms should be interpreted with caution. For example, even if the conclusion drawn by both papers is correct, it does not follow that this conclusion is valid for all genes. There may still be unknown genes that offer support to the rival theory.

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