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Science 6 February 2009:
Vol. 323. no. 5915, p. 714
DOI: 10.1126/science.1166571
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Technical Comments

Response to Comment on "Human-Specific Gain of Function in a Developmental Enhancer"

Shyam Prabhakar,1* Axel Visel,1 Jennifer A. Akiyama,1 Malak Shoukry,1 Keith D. Lewis,1{dagger} Amy Holt,1 Ingrid Plajzer-Frick,1 Harris Morrison,2 David R. FitzPatrick,2 Veena Afzal,1 Len A. Pennacchio,1,3 Edward M. Rubin,1,3{ddagger} James P. Noonan1{ddagger}§

Duret and Galtier argue that human-specific sequence divergence and gain of function in the HACNS1 enhancer result from deleterious biased gene conversion (BGC) with no contribution from positive selection. We reinforce our previous conclusion by analyzing hypothesized BGC events genomewide and assessing the effect of recombination rates on human-accelerated conserved noncoding sequence ascertainment. We also provide evidence that AT -> GC substitution bias can coexist with positive selection.

1 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
2 MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
3 United States Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.

* Present address: Computational and Mathematical Biology, Genome Institute of Singapore 138672, Singapore.

{dagger} Present address: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

§ Present address: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

{ddagger} To whom correspondence should be addressed. E-mail: EMRubin{at}lbl.gov (E.M.R.); james.noonan{at}yale.edu (J.P.N.)

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Science. ISSN 0036-8075 (print), 1095-9203 (online)