[Menydh]

Conclusion

The hypothesis of regulatory evolution put forward by King and Wilson 30 years ago was founded entirely on negative data, that is, the apparent insufficiency of coding sequence divergence to account for gross organismal differences. It has required several decades to obtain evidence that regulatory sequences are so often the basis for the evolution of form that, when considering the evolution of anatomy (including neural circuitry), regulatory sequence evolution should be the primary hypothesis considered. The analysis of regulatory sequence evolution poses particular challenges in that it is impossible to distinguish meaningless from functional changes by mere inspection. But, in nonhuman models where extensive experimental tools are available, there is cause for optimism that the contribution of regulatory sequences to evolution will be increasingly well understood in the near term. In order to approach the origins of human traits, much greater emphasis has to be placed on comparative studies of gene expression, regulation, and development in apes and other primates. This is precisely the requirement forecast by King and Wilson 30 years ago [1], only now we have the means to meet it.

Acknowledgments

I thank M.-C. King for correspondence regarding her 1975 paper with A. C. Wilson, L. Olds for the artwork, and A. Rokas, B. Williams, C. Hittinger, B. Hersh, P. Carroll, and S. Paddock for helpful comments. Work in my laboratory is supported by the Howard Hughes Medical Institute.