Robert Wood Johnson Medical School, Piscataway, New Jersey

A molecular biophysicist muses on how a vital structural protein might have turned out differently.

One thing I love about science is its surprises. One signature eukaryotic protein is actin, a cytoskeletal protein involved in cell migration and muscle contraction. Few would have guessed that actin has a similar structure to proteins with little sequence homology or shared function beyond hydrolysis of the energy-storage molecule ATP.

Some prokaryotic cytoskeletal proteins share actin's folding pattern and, like actin, can form filaments. Electron microscopy initially indicated that the filament structure of the DNA-segregation protein ParM, for example, is similar to actin's. With improved methods, Orlova et al. revealed another surprise: ParM's helix winds in the opposite direction to actin's (A. Orlova et al. Nature Struct. Mol. Biol. 14, 921–926; 2007). The main differences between actin and ParM filaments are in contact regions between subunits, which are crucial for constructing this new molecular model of the filament.

If we consider each evolutionary change as a 'mutagenesis experiment', the number required for a common ancestor to become actin or ParM is mind-boggling. There would be new functions and failures along the way — even a single amino-acid substitution in haemoglobin can cause sickle-cell anaemia. Without a record of genetic changes we cannot know the intermediate successes and failures, as we do for some bizarre invertebrates found in the fossil record. Stephen Jay Gould recounts these discoveries in Wonderful Life, in which he warns of being bound by conventional thinking.

Eukaryotic life settled on the actin filament, constrained by evolution to be dynamic, to work with its motor protein, myosin, and myriad binding proteins. Just think, if actin filaments had different inter-subunit contacts — such as those in ParM — myosin would be unable to bind to it, an important helical protein, tropomyosin, would coil in the wrong direction for binding along the filament and ... well, it's like me wondering what I would be like if I had a different father.