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Head in Hand

Is handedness genetic? The question is centuries old and has been the subject of hundreds of scientific papers. Now, the verdict is finally in, and the answer is yes. But there is an unexpected twist to the story: It seems that the same gene that creates lefties also determines which way hair whorls around.

Amar Klar, the head of developmental genetics at the National Cancer Institute campus in Frederick, Maryland, explained the link between handedness and the way hair spins on the scalp in the September 2003 issue of Genetics. It seems a single gene with two alleles controls both traits. The dominant allele dictates right-handedness—and a clockwise hair spiral. So having even a single copy yields a right-handed (or dexter) bias, as is the case for most people. Having only the recessive version, rather than causing left-handedness (or, as Klar would say, "non-right-handedness," to include the ambidextrous), does not direct any preference at all and results in a 50:50 mix of righties and nonrighties. In addition to generating southpaws half the time, two copies of the so-called "random-recessive" allele lead to a (separate) 50:50 chance of having their heads spin counterclockwise.

So if you've got a counterclockwise pattern on your dome (only appearing in 8 percent of the population), you're certain to have two copies of the random-recessive allele, but you have only a 50 percent chance of being a lefty. Likewise, people who are predisposed to be sinister (from Latin, meaning "on the left") are definitely carrying two recessives, but only half of these people will sport a counterclockwise whorl.

Hair whorls often (but not always) reveal handedness . . .Click to Enlarge Image

The random-recessive model explains the two big conundrums about genetic theories of handedness: Half of the children of a pair of left-handed parents are right-handed, and, even more confusing, 18 percent of identical twins are discordant for hand preference. How could the trait be genetic if two people with the same genes showed different handedness? It's no wonder that psychologists adopted the view that handedness is (at least partially) a learned behavior.

Instead of looking at handedness-discordant twin pairs as an unfortunate thorn in the side of genetic theories, Klar availed himself of the natural experiment and continued to follow the progeny of such twins. The surprising result was that the right-handed twin was just as likely to have left-handed children as was his or her left-handed double, and both dexter and sinister members of the discordant pair had the same likelihood of siring a young southpaw as did other lefties in the general population. According to Klar, his is the only analysis of handedness-discordant twins that has examined the hand preference of their offspring.

The bizarre connection with the direction of hair coiling is likely to be a result of events during embryogenesis. Both neural tissue and skin come from ectoderm, one of the first differentiated layers of cells that begin to appear during development. Other asymmetric anatomical features—such as placement of the heart and liver—are products of different layers, the mesoderm and endoderm. This fact might explain why the heart is invariably on the left, but neurologically derived hand preference and hair whorl are less constant.

Klar is a pioneer in the abstruse field of mating-type switching in yeast, and he admits that his studies of handedness started as "sort of my hobby." Not surprisingly, he is somewhat iconoclastic in his new field. In the face of numerous genetic theories that proffer complex hypothetical mechanisms, he responds, "I'm a yeast geneticist. I don't use the term 'penetrance.'" He continues, "when you read the literature [on handedness], it leaves a sour taste in your mouth. You get more confused than when you started." So how did he get from the fission yeast Schizosaccharomyces pombe to the murky and inflamed realm of nature-versus-nurture polemic? Klar's catholic interests center around a common theme of asymmetry.

More than a decade ago, Klar showed that in fission yeast, daughter cells assume different fates depending on which DNA strand they inherit—even though the strands are complementary and were long presumed to carry identical information. Under the exhortations of his Cold Spring Harbor mentor, James Watson, he studied the differences between the "Watson" and "Crick" strands, which became known as the "strand segregation model," and started thinking about other forms of asymmetry. In addition to handedness research, he has published papers about the biological demonstrations of the mathematical Fibonacci series in plants and the laterality of various brain functions.

It is no coincidence that humans are the only animals with genetic hand preference and a unique facility for language. Although 97 percent of right-handers have speech centers in the left hemisphere, the value for left-handers is between 50 and 70 percent. This lack of explicit asymmetry, although associated with many positive attributes, may predispose nonright-handers to schizophrenia and bipolar disorder: The incidence of left handedness among people with these psychoses is three times higher than among the general population.

Ultimately, it is this possibility that drives Klar's research into hand preference. Well, that and the urgings of Jim Watson, a lefty, who has been "constantly nagging me to map the handedness gene." By identifying the relevant locus, Klar hopes to gain insight into the "final cause of schizophrenia." He may be on the right track. In 2002, he characterized a large family with a unique mutation that in exactly half of its carriers—but no other family members—led to schizophrenia or bipolar disorder. This suggests that the mutation might help explain both asymmetry and schizophrenia. Now that deserves a hand.—Chris Brodie

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