Illustration by Christoph Niemann


The Paper: Placental-specific IGF-II is a major modulator of placental and fetal growth

The Journal: Nature, June 27, 2002

The Authors: Miguel Constancia, et al.

The Gist: A battle of the sexes is taking place in your genes.

Before Translation: “Lack of the PO transcript with paternal transmission of the deletion resulted primarily in placental growth restriction. Placental growth was impaired as early as embryonic day 12 (E12), when the mean weight of mutant placentae was 76 percent of wild-type placentae (average (in g) standard error: +/+, 0.030 0.001, n = 27; +/-, 0.023 0.001, n = 25; P 0.001)."

Men and women fight tooth and nail over lots of things -his couch potato habits, her spending sprees, his two-timing ways. But there’s much more to the battle of the sexes. Male and female genes often duke it out for dominance, especially the genes that control an embryo’s development.

The notion that genes have their own ruthless motives has been widely accepted since the 1970s, when Oxford University zoologist Richard Dawkins published The Selfish Gene. Scientists have since uncovered many specific examples of genes that, for their own benefit, sabotage other genes. The selfish DNA theory just got another boost from a group led by Miguel Constancia, a developmental biologist at Babraham Institute in Cambridge, England. Constancia has shown that the male and female genes that govern placental nutrition are at odds with one another. He deleted a portion of a gene called insulin-like growth factor (Igf2) from male mice. He then used their sperm to fertilize females. The resulting young-which lacked a portion of their paternal Igf2 gene-turned out much scrawnier than normal.

For most genes, two copies are active, one from mom, the other from dad. But sometimes only one of the pair actually makes proteins. In the case of Igf2, the maternal gene is said to be silent-that is, only dad’s gene makes the protein that allows nutrients to pass from mothers to their babies through the placenta.

Scientists call this phenomenon, whereby one gene beats out another, genomic imprinting. This trait is shared by all mammals, but not other animals, causing scientists to wonder how and why genomic imprinting evolved. The answer, Constancia and many others believe, is competition between male and female genes.

In animals that develop without placentas (a chick inside an egg, for example), embryos have a fixed amount of nutrients. In mammals, however, an embryo gets nutrients from its mother. So it’s in mom’s interest to have a small baby, in order to spare her health. But dad’s genes are greedy: All they care about is having big healthy babies. Mom’s health is incidental, and so an evolutionary conflict arose. The ultimate resolution: babies that are middleweights. Hence, when Constancia deleted the paternal gene, the mother’s silent gene won out and she got a smaller baby.

Constancia has a hunch that smaller-than-normal human babies might result from problems in imprinted genes. Other ills, such as Prader-Willi syndrome (which causes morbid obesity, mental impairments, and other abnormalities) have already been shown to occur when a baby lacks its father’s copy of a gene. Of course, plenty of other factors can cause babies to be born abnormally small, but Constancia and colleagues are planning to screen the placentas of low-birth-weight babies to look for abnormalities in their paternal Igf2 genes. If Constancia is right, in the future such abnormalities could be
relatively easy to spot-and easy to treat.