How the snake lost its legs. No, this isn’t a Just So story a la Rudyard Kipling, but a fascinating paper in Cell (vol. 167 pp. 598 – 600, 633 – 642 ’16 ). All it takes is a 17 nucleotide deletion in ZRS (Zone of polarizing activity Regulatory Sequence), an enhancer of gene expression involved in limb development. The enhancer is at least 1,300 nucleotides long (but I can’t find out just how long ZRS is). The deletion removes a binding site for a transcription factor (ETS) which turns on some limb development genes.
ZRS has long been known to be involved in limb development, and mutations distributed over 700 nucleotides are associated with a variety of human limb malformations. So the authors sequenced the enhancer in a variety of species (including many snakes) and found that only snakes had the deletion.
Then they put the snake ZRS into genetically engineered transgenic mice and found markedly shortened limbs. That was all it took. Reintroducing the missing 17 nucleotides into the transgenics restores normal limb development. Staggering what genetic technology is capable of.
Where does the butterfly effect come in? Because the enhancer is 1,000,000 nucleotides away from some of the genes it controls. If you were studying sequences around the genes it controls, you’d never find the deletion (until you’d run through a large number of grad students). Human biology (with limb malformations) told the authors where to look.
Straightened out 1,000,000 nucleotides is 3,200,000 Angstroms,or 320 microns (32 times the size of the average 10 micron nucleus). Remarkable how it finds its target. You might be interested in a series of posts which try to imagine these goings on at human scale — blowing up the nucleus so it fits in a football stadium with our double stranded DNA blown up to the size of linguini with a total total length of 2840 miles. Start here –https://luysii.wordpress.com/2010/03/22/the-cell-nucleus-and-its-dna-on-a-human-scale-i/