chr6 · 6p22 · 255 nt · 2006

HAR5

What it is

Not every HAR is a new volume knob. HAR5's pattern is substitutions that compensate for each other, some deleted ancestral sequence, and a change in how the region folds. The gene nearby stays the same; the neighborhood does not.

Why it matters

Shows loss and topology, not only enhancer gain.

Operator load

• 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.

• 05 · L

  Deletion and loss

  Human evolution also deleted ancestral DNA. Removing an old brake can let a developmental program run longer or start earlier.

• 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.

Pollard et al. 2006 · McLean et al. 2011 hCONDELs