The Evo-Devo Puzzle of Human Hair Patterning

Humans differ from all other living primates in the sparseness of our hair. Even more puzzling than the overall reduction in our fur covering is the layout of the few tufts that remain. Why does hair grow mainly on our scalp, armpits, and groin? How does our genome designate these areas? Clues to the underlying mechanism can be found in mouse mutants and human syndromes, but the mystery remains essentially unsolved. This essay reviews the evidence, pieces together the clues, and formulates a tentative hypothesis in the style of a Sherlock Holmes story. The deductive reasoning of the narrative is aided by what we already know about an analogous locus in the fruit fly that performs a comparable function. Homo sapiens are the only ‘‘naked apes,’’ though this phrase, popularized by Desmond Morris, is somewhat misleading. We still have a profusion of hair on our scalp and, as children, the rest of our body makes a fine, transparent ‘‘peach fuzz’’ called vellus. Indeed, the only truly hairless areas of our body are our palms, soles, lips, and parts of our genitalia (Martini et al. 2004). Why did our hominin ancestors lose so much fur? Our best guess is that fur became a liability when they started running long distances and began to suffer from overheating (Jablonski 2010). Under those conditions any mutations that lessened our insulation would have spread through the population. Which genes were impacted? No hair-affecting genes have yet been found among the loci that show evidence of selective sweeps (Enard et al. 2010). We have little hope of solving this evolutionary riddle until we figure out how hair patterns are delineated during development. Why, for example, do cells in our scalp make stout, pigmented ‘‘terminal’’ hair, whereas nearby cells on our forehead make invisible vellus? How are such boundaries drawn? Put simply, the core issue here is: How is the two-dimensional jigsaw puzzle of hairy versus smooth territories within our skin controlled by our (one-dimensional) genome? Some enticing clues are available in the literature of human syndromes and mouse genetics, but they have not yet been fitted together into a testable model of genetic circuitry. Before examining the evidence, it might help if we had at least a vague idea of what kind of circuitry we’re looking for. The best known ‘‘area code’’ directories in animal genomes are the Hox (homeobox) gene complexes (Lemons and McGinnis 2006). They designate body regions along the head–rump axis of our skeleton, nervous system, and branchial arches (Held 2009), but none of those zones coincides with our hairy territories (Duboule 1998a). Moreover, Hox complexes are atypical insofar as they exhibit the odd property of colinearity (Wray 2003), where the order of genes along the chromosome matches the order of structures along the body (Duboule 1998b). Generally speaking, animal genes are regulated by ‘‘cis-enhancers’’ (i.e., adjacent DNA elements), whose order is scrambled relative to the body parts they control (Swanson et al. 2010). A more typical circuit is the even-skipped locus in the fruit fly (Zeitlinger and Stark 2010), where the order of stripespecific enhancers along the DNA does not reflect the order of expression stripes along the embryo (Borok et al. 2010).