chr10 · 10p11.21 · 1200 nt · 2015

HARE5

FZD8 enhancer

What it is

HARE5 is a human-accelerated enhancer of Frizzled-8, a Wnt receptor used by neural stem cells. When the human sequence is placed in a mouse, progenitor cells divide a little longer and the neocortex grows. This is one of the few HARs with a direct experimental growth phenotype.

Why it matters

Causal enhancer-to-brain-size experiment.

Operator load

• 01 · ΔE

  Enhancer activity

  These stretches of DNA do not code for proteins. They act as volume knobs — turning nearby brain-development genes up or down at the right moment.

• 02 · C

  Compensatory substitution

  When one letter in the sequence changes, another often changes to keep the whole switch working. Evolution rewired the circuit without breaking it.

• 03 · T

  Three-dimensional rewiring

  The genome folds in 3D. Human-specific changes can re-route which switches sit next to which genes, even if the letters look similar in a straight line.

• 06 · P

  Population spread

  Once a change is useful, it spreads. Many HAR variants rose quickly in ancestral humans and are now nearly fixed across living populations.

Boyd et al. Curr Biol 2015