Sixty years on from the publication of Watson and Crick’s double helix DNA structure, Genome Biology has asked their Editorial Board members to name the discoveries and inventions in the field of genome biology that they deem to be the most important or surprising, or that have had the greatest personal impact to them.
A clear favorite emerged, and one which suprisedthe Editors – the discovery of introns was selected by a third of contributors to the article. Steven Henikoff and W Ford Doolitle expand upon their selection of introns here, and the full article appears in Genome Biology today.
I was just finishing up as a graduate student in 1977 when I first learned of the amazing discovery of split genes in adenovirus. Shortly thereafter, rumors circulated that genes in pieces, or what Wally Gilbert referred to as exons and introns, are far more common than originally supposed, and in fact are the rule, rather than the exception. It was a thrill to realize that something that we all took for granted, from the dominant E. coli paradigm of uninterrupted protein-coding genes, does not hold in eukaryotic genomes. It is hard to think of another example in which a concept so fundamental as split genes and post-transcriptional splicing was not suspected to exist before its discovery. Wally began the debate over ‘why?’ and others asked ‘how?’, but for me, the question was: what other surprises lay in store in the realm of eukaryotic gene organization? Thus began my interest in what later became referred to as genomics, and when I had my own lab, studying genes in pieces led to the surprising discovery of genes in pieces in genes in pieces.
Steven Henikoff, Fred Hutchinson Cancer Research Center.
The discovery of spliceosomal introns in the genomes of eukaryotes ranks very near the top of my list, in ‘significance, surprise and (especially) personal impact’. I was at the time (1977) on sabbatical in the lab of Wally Gilbert and he, having just become aware of that amazing discovery, came up with ‘exon shuffling’ as an appealing raison-d’etre for introns’ existence. Because I also knew of Carl Woese’s then very recent discovery of archaea and Carl’s inference therefrom that eukaryotes and prokaryotes might have diverged separately from a more primitive common ancestor, and because I did not believe that early eukaryotes would have taken on the burden of introneousness just because it might help them in the distant future, I cobbled together the theory that became known as ‘introns early’.
Almost certainly that theory is false: it seems much more likely that spliceosomal introns are Group II introns gone to seed – fallen apart into ‘five easy pieces’ and increasingly dependent on dozens of proteins, the accretion of which may have been largely through a neutral evolutionary ratchet. But ‘introns early’ had a great run, in large part thanks to Wally, and stimulated many to think more deeply about the evolution and functional significance of genome architecture. In particular, it forced us to accept that Dobzhansky’s rubric that “nothing in biology makes sense except in the light of evolution” is just as valid at the molecular level as the organismal. Genomes are much more than repositories of encoded information needed to make organisms, and we can be led astray if we adopt an overly functionalist/adaptationist perspective. Genomicists and systems biologists are especially at risk for doing this, as the recent controversy surrounding the ENCODE project illustrates.
W Ford Doolittle, Dalhousie University