Did a gene enhancer humanize our hands?

Researchers have identified a noncoding sequence in the human genome that enhances gene expression in the developing hand and forelimb, particularly at the junction of the wrist and thumb, researchers report in the Sept. 4 issue of Science. The sequence, called HACNS1, evolved rapidly in humans compared to chimpanzees and macaque monkeys, and may have played a role in "humanizing" our hands and feet, according to Shyam Prabhakar and colleagues. By creating mouse embryos with the HACNS1 sequence, the researchers were able to observe its effect on gene expression in the developing forelimb and hindlimb, but it's still unclear which gene or genes are targeted by the sequence. It does seem that HACNS1's "enhancer" function is unique to humans, however.

Some genes are served by multiple enhancer sequences, including some that share duties with a primary enhancer but are found far from the target gene. Joung-Woo Hong and colleagues' Drosophila studies suggest that these "shadow enhancers" evolve more rapidly than their related primary enhancers, opening the door to new ways to regulate a particular gene without disrupting its core function. In a related Perspective, Gregory Wray and Courtney Babbitt discuss how Prabhakar, Hong and their colleagues approached the challenge of searching for noncoding regions of the genome that have far-reaching regulatory effects.

ARTICLE #17: "Human-Specific Gain of Function in a Developmental Enhancer," by S. Prabhakar; A. Visel; J.A. Akiyama; M. Shoukry; K.D. Lewis; A. Holt; I. Plajzer-Frick; V. Afzal; L.A. Pennacchio; E.M. Rubin; J.P. Noonan at Lawrence Berkeley National Laboratory in Berkeley, CA; H. Morrison; D.R. FitzPatrick at MRC Human Genetic Unit, Western General Hospital in Edinburgh, UK; L.A. Pennacchio; E.M. Rubin at U.S. Department of Energy Joint Genome Institute in Walnut Creek, CA; S. Prabhakar at Genome Institute of Singapore in Singapore, Singapore; K.D. Lewis at California Institute of Technology in Pasadena, CA; J.P. Noonan at Yale University School of Medicine in New Haven, CT.

ARTICLE #9: "Shadow Enhancers as a Source of Evolutionary Novelty," by J-W. Hong; D.A. Hendrix; M.S. Levine at University of California, Berkeley in Berkeley, CA.

ARTICLE #4: "Enhancing Gene Regulation," by G.A. Wray; C.C. Babbitt at Duke University in Durham, UK.