Distorting sex ratios.

D uring sperm production in mammals, the process of meiosis generates sper-matozoa that are genetically different but functionally equivalent. So, with respect to the sex chromosomes, for example, equal numbers of sperm are produced carrying either an X or a Y chromosome. Because X and Y sperm are equally capable of fertilizing an egg, equal numbers of male and female embryos are produced, and the mammalian sex ratio at birth is 50%. All other pairs of chromosomes show this 50% transmission ratio, but there are rare exceptions. For example, some mice contain naturally occurring variants of chromosome 17 — the so-called t-haplotypes — that do not obey this rule. Remarkably, sperm carrying these unusual chromosomes can propagate themselves with transmission ratios as great as 99% in their own favour. It was not known how this process, known as transmission ratio distortion (TRD), is achieved at a molecular level. But on page 141 of this issue, Herrmann and colleagues 1 describe a unique protein kinase encoded by the t-haplotype. This kinase affects a signal-transduction cascade that probably controls the speed and directionality of sperm as they make their long journey up the female reproductive tract. Within a mouse t-haplotype, several hundred functionally unrelated genes have been locked together by a series of chromo-somal inversions that prevent recombina-tion with wild-type chromosomes 2. All t-haplotypes derive from a single common ancestor, and wild mice carrying these chromosomes can be found all over the world. The t-haplotype variants (known as t w12 , t w32 and so on) differ in the functionally unrelated genes, but not in the TRD system. Presumably, it is the common TRD system that allowed the successful propagation of t-haplotypes. Over 40 years ago, Mary Lyon began a genetic study of TRD in the t 6 haplotype of laboratory mice. She eventually developed a model for TRD, involving interactions between three or more genetic loci 3–5. According to this model, several loci — the t-complex distorters, Tcd — act on the single t-complex responder locus, Tcr, to distort transmission ratios (Fig. 1a). Normally , of course, all the component genes of the TRD system are encoded in the t-region of chromosome 17, and are locked together by the chromosomal inversions. But experiments have shown that the distorters (Tcds) can act in trans on the cis-acting Tcr respon-der 3. Put more simply, this means that the