ABOLT 370 million years ago, in the latter part of the Devonian, the ancestor of all terrestrial vertebrates stepped out of the ocean and began to take advantage of the untapped wealth found on land. This was a big step, both literally and figuratively, and evolution biologists have long believed that the coincidental coincidence of several genetic mutations required to effect the anatomical shift from functional fin to proto-leg. However, this may not be the case. An article just published in Cell, by Brent Hawkins, Katrin Henke and Matthew Harris of Harvard University, suggests that the process was propelled by a single genetic alteration of the smallest possible kind.
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To better understand the origins of tetrapods, as terrestrial vertebrates are collectively known to zoologists, the trio looked at what happened to zebrafish (a common topic of developmental biology experiments because they are small, transparent, and breed a lot) when they became minor adaptations to the genes of those fish. When searching over 10,000 mutated specimens, they found that a group of mutants had an unusual bone pattern in their pectoral fins. Instead of four, they had six.
Interestingly, the extra pairs were some distance from the body, and the involved bones lay parallel to each other like the radius and ulna do in the forelimb of a tetrapod (see diagram). Additionally, and even more intriguingly, the two new bones were neatly integrated with the fin muscles and well articulated with the rest of the local skeleton. Most intriguing of all, however, this significant anatomical shift was brought about by the replacement in a single type of protein molecule, called Wasl, of a few of its amino acid building blocks.
Wasl is a signal protein. But it’s not one that, as far as the team could see from embryonic development literature, was previously associated by anyone with the process of limb formation in vertebrates. However, an experiment they then performed in mice, in which the gene encoding Was1 was turned off, resulted in deformation of the relevant bones in all four limbs of the rodents, not just the forelimbs. Thus, it is clear that this protein does indeed play a role in tetrapod limb formation.
The most recent common ancestor of zebrafish and mice even predates the Devonian. That gives a lot of time to change patterns of embryonic development in the lines leading to those two species – and, specifically, to have changed in the way the fins of modern fish develop. So the fact that the mutation the team discovered today only affects the pectoral fin does not preclude the possibility that it has now also stimulated the arrival in the pelvic fin of the mouse fish precursor of the bones. known as the fibula and tibia. It therefore seems very possible that Drs. Hawkins, Henke, and Harris may have found the source of the crucial change that allowed the ancestor of mice – as well as humans – to scramble ashore and leave the sea behind.
This article appeared in the Science and Technology section of the print edition under the heading “ Getting Ahead ”