Enhancer
Human-Specific Gain of Function in a Developmental Enhancer
08/09/2008
Changes in gene
regulation are thought to have contributed to the
evolution of human development. However, in vivo
evidence for uniquely human developmental regulatory
function has remained elusive. In transgenic mice, a
conserved noncoding sequence (HACNS1) that evolved
extremely rapidly in humans acted as an enhancer of
gene expression that has gained a strong limb
expression domain relative to the orthologous
elements from chimpanzee and rhesus macaque. This
gain of function was consistent across two
developmental stages in the mouse and included the
presumptive anterior wrist and proximal thumb. In
vivo analyses with synthetic enhancers, in which
human-specific substitutions were introduced into the
chimpanzee enhancer sequence or reverted in the human
enhancer to the ancestral state, indicated that 13
substitutions clustered in an 81–base pair module
otherwise highly constrained among terrestrial
vertebrates were sufficient to confer the
human-specific limb expression domain.
Science 5 September 2008: Vol. 321. no. 5894, pp. 1346 - 1350
DOI: 10.1126/science.1159974
Science 5 September 2008: Vol. 321. no. 5894, pp. 1346 - 1350
DOI: 10.1126/science.1159974
|