Nature Genetics pp 362 - 365 and pp 315 - 316

Genes are usually inherited as two active copies, one from each parent. For a subset of genes, however, only one copy is active; for these genes, the active copy is always inherited from the mother or, in other cases, it is always passed on from the father -- this phenomenon is known as imprinting. Having only one active copy of a gene means that there is no backup if that copy is defective; it is puzzling that nature should appear to have a rebel without a cause. Scientists have observed that some genes controlling growth of the embryo are imprinted in a specific way -- those that promote growth are only active when inherited from the father, and those that suppress growth are inherited from the mother. This lends support to the idea that gene imprinting arises from a 'conflict' between the sexes. The father wants to propagate his own genes and therefore tries to ensure that his offspring are the biggest and fittest (at whatever cost to the mother). The mother, on the other hand, tries to minimize the drain on her resources by limiting the size of embryo to ensure that she will be able to bear future offspring.

The battle between the sexes, however, may not fully explain gene imprinting, as suggested in a new study by Shirley Tilghman, of Princeton University, and colleagues. Imprinting is thought only to occur in promiscuous animals, where individuals mate with different partners -- leading to competition over whose genes are passed on to the next generation. Truly monogamous animals are not expected to have imprinted genes because the sexes are not in 'conflict'; both parents have an equal interest in maintaining the reproductive prospects of the other -- thereby maximizing their respective chances of having additional offspring that carry their genes. Tilghman and coworkers analysed a polygamous and a monogamous species of the rodent Peromyscus and found, unexpectedly, that imprinted genes are not only present in the promiscuous but also in the monogamous species.

Upon mating the polygamous and monogamous Peromyscus species, the scientists observed hybrid offspring with severe growth defects. Offspring were either drastically growth retarded or extremely oversized -- and rarely survived. The expression of imprinted genes in the hybrid offspring was abnormal compared with that of the parent species, suggesting that imprinted genes may prevent related species from inter-breeding and might provide a means by which new species evolve.

In an accompanying News & Views article, Laurence Hurst, of the University of Bath, discusses the findings and concludes that it might be time to start thinking about new explanations for imprinting.

Nature Genetics pp 353 - 357 and pp 318 - 319

Being female by 'default' has been a popular theory in developmental biology circles. It started in the 1950s with studies in rabbits demonstrating that the removal of testes from a male embryo resulted in a female rabbit, whereas removal of ovaries from a female embryo did not change its sexual destiny. It was therefore thought that all of us have the potential to develop as females, but it is the overlay of the testis and male-specific factors that send some of us down the masculine route. This 'default' idea was subsequently rebuffed by evidence suggesting that attaining female sex differentiation is an active process, requiring female-specific factors to program ovarian development. A candidate for such a female factor is AHC (also known as DAX1), a gene on the X chromosome. Men normally have only one copy of the AHC gene, whereas women have two copies. A double dose of AHC in men, as a result of accidental duplication of the gene, causes males (genetically defined as carrying an X and a Y chromosome) to develop the sexual characteristics of females.

Larry Jameson, of Northwestern University Medical School, and colleagues have now made the surprising observation that the absence of Ahch (the mouse equivalent) in female mice does not affect ovarian development and fertility. Rather, it is males that suffer without Ahch -- male mice deficient in Ahch have abnormal testes and are sterile. These findings indicate that Ahch determines male, rather than female, sexual development. In an accompanying News & Views article, Keith Parker, of UT Southwestern Medical Center, and Bernard Schimmer, of the University of Toronto, discuss the role reversal of Ahch in sexual development. In light of this recent report, it might be tempting to revisit the old theory that female development occurs by default, but it may simply be that the feminine mystique is refractory to genetic dissection.

Nature Genetics pp 337 - 343 and pp 316 - 317

Respiration is a process that produces the energy needed to keep a cell alive. It occurs in tiny capsules inside the cell called mitochondria. The respiratory process takes place through the activity of a series of enzymes located along the inner membrane of mitochondria. Disruption of this respiratory chain, as is the case in several human neurodegenerative diseases, compromises energy production throughout the body and causes the greatest damage in those tissues with the highest energy demand -- in particular, the brain. Leigh Syndrome (LS), a severe neurological disorder characterized by necrotic lesions in the brain, is associated with a defect in cytochrome c oxidase (COX), a critical and final 'link' in the respiratory chain. COX is made up of several subunits, each of which is encoded by a different gene -- surprisingly, none of these genes are mutated in LS patients. Eric Shoubridge, of McGill University, and colleagues now reveal that mutation of the SURF1 gene is the underlying genetic defect in LS. The function of SURF1 is presently unknown, but, as discussed by Robert Poyton, of the University of Colorado, in an accompanying News & Views article, studies of the equivalent gene in yeast indicate that SURF1 may function as a 'facilitator' for the proper assembly of the different COX subunits.