BioWorld International Correspondent

LONDON - The latest evidence that the expression of a gene can depend on which parent it was inherited from has important implications for researchers engaged in studying genetic phenotypes. One of the scientists who carried out the work suggests the findings may have a particular bearing on studies aimed at elucidating the genes that influence early human growth.

Reinmar Hager, a Ph.D. student working with Rufus Johnstone of the department of zoology at the University of Cambridge, has shown that the genetic strain of male mice helps to determine the litter size of their mates. The genetic strain of the female had no such effect.

The explanation for this finding may lie with imprinted genes. Those are genes in which only one allele is active in producing the encoded protein. With maternally expressed genes, only the allele inherited from the mother is expressed; with paternally expressed genes, only the allele inherited from the father is expressed.

Hager told BioWorld International, "This study highlights how important it is to analyze the effects of imprinted genes. Genes of this kind are known to influence prenatal and postnatal growth in mice and although we have no experimental evidence for the same effects in humans, we are mammals, too, and so it is not too far-fetched to assume that you might get a similar effect.

"In order to understand early human growth, it will definitely be important to look at the different interests of males and females, which can be mediated by parent-of-origin-specific effects such as genomic imprinting."

It also will be vital for those carrying out more general research into gene function to consider whether the gene under scrutiny might be imprinted, he predicted, especially when examining the phenotypes that result from knocking out genes. "It may be that the effects they observe depend not only on the gene itself but also on the sex that the gene was inherited from. There is a distinct need for more research to examine these kinds of effects in mouse models," Hager said.

The study by Hager and Johnstone is reported in the Jan. 30, 2003, issue of Nature in a letter titled "The genetic basis of family conflict resolution in mice."

The theoretical background behind their study is the idea that conflicts exist in families over allocation of resources. As Hager explained, "It is all about who gets how much parental investment, and who has to pay for it. In mammals, the male does not contribute very much to raising the offspring, whereas the female has to invest quite a lot during pregnancy and lactation. The male wants the female to invest more than is optimal for her. She wants to resist this because if she invests too much in his litter, this may weaken her and reduce her ability to rear more litters in future."

Hager said, "We wanted to know what were the effects of maternally inherited genes and of paternally inherited genes on the offspring, and of how genes expressed in the mothers acted to resolve this conflict, in terms of how much resources are given to the young."

They did this by crossing two strains of mice, CBA, which produce large litters, and B6, which produce smaller litters but have larger pups at birth. They found that, apart from maternal body weight, the only factor that had a significant influence on the size of the litters was the strain of the father.

Their next step was to foster pups of all four genotypes with unrelated females, which were either CBA or B6. To simulate the animals' natural behavior, they removed the females from the pups for two hours before replacing them. The amount of milk delivered to the pups was estimated by measuring the female's weight loss.

They found that CBA females reduced the amount of milk they allowed the young to take. "It seems that the females that have to produce a large litter because of the paternal effect compensate for the costly effects of this by reducing provisioning to their unrelated young," Hager said.

Pups that were fostered by CBA mothers gained more weight if their natural mother was CBA than if she was B6, but the strain of their father did not make any difference. Hager said, "This shows this effect is not just a property of the CBA genome in general, but it depends on whether the pup inherited the relevant set of genes from a male or a female."

He speculated that the paternal effect on litter size could be due to a gene that expresses a signal that dictates whether or not embryos are resorbed in the uterus.

Future research by Hager and Johnstone will include an examination of whether there are any paternal effects that influence how siblings compete for resources - put simply, whether paternal influence can make offspring more greedy.