Like Living without Running Water
It still amazes me how, back in the “old days”, discoveries of base-substitutions, frame-shift mutations, deletions, the genetic code, nonsense mutations, transposons, and gene mapping were done all without the availability of DNA sequencing, which started to come into major use in the mid-1970s. For example, the discovery that transposons (or “jumping genes”) were surrounded by DNA sequences of inverted repeats was done not by DNA sequencing, but by electron microscopy. Yes, electron microscopy. Researchers concluded after seeing that the transposons could form cruciform stem-loop shapes that they had such inverted repeats.
How cave men might have looked for inverted repeats
This is an amusing paragraph:
“[One researcher] found [transposon-like insertions] which do not have detectable inverted repitition….These insertions may represent a different type of [transposible] element, or may be cases in which the inverted repetition is too short or too unstable to be detectable by standard visualization methods which depend on intramolecular annealing. [i.e. electron microscopy]” (from Kleckner et al. (1975) J. Mol. Biol., 97, 561-575.)
Seriously, this paper sounds like something from the dark ages. Nowadays, any reasonably skilled undergraduate would be able to just sequence the darn thing, showing without a doubt whether the inverted repeats are there or not.
Just reading these old papers makes me sympathize with the researchers in the 1990s who wanted to sequence the hell out of everything they could find (and they’re still out there). I mean, when compared to technology like this, sequencing must have seemed like the be-all-end-all of molecular biology!
