The silence of genes

Although the discovery of genomic imprinting dates back more than two decades, its significance for both disease pathogenesis and evolutionary theory is only now emerging. However, its effects had been observed for much longer, and if biologists had been influenced less by prevailing orthodoxies, they might have stumbled on it sooner. Mule breeders encountered the phenomenon three millennia ago, when they observed that a female horse crossed with a male donkey yielded a mule, whereas a male horse crossed with a female donkey gave a ‘hinny’. The mule has longer ears, whereas the hinny has stronger legs and a thicker mane. The differences between the mule and the hinny are now known to be caused by genomic imprinting, whereby the expression of a gene is determined by its origin rather than its DNA sequence. This phenomenon had previously been largely discounted because of the powerful influence exerted by Gregor Mendel’s rules of inheritance. Mendel asserted that phenotype was determined entirely by the underlying alleles and was independent of any other parental or environmental factors. This in turn led to the complete dismissal of alternative theories, notably from Jean-Baptiste Lamarck, who proposed that acquired characteristics could be inherited. The discovery of genomic imprinting neither overturns Mendelian inheritance nor restores Lamarckism. However, it does muddy the waters, and identifies an important mechanism of inheritance and evolution that Mendel missed.