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How to Make a Uterus

8 October 2004 (All day)
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Shape of things to come. Changes to two Hox genes may have spurred evolution of the mammalian female reproductive tract.

When the female ancestors of today's mammals evolved a uterus, placenta, and vagina, their egg-laying days were over. Now researchers have identified two genes that they suspect played a key role in creating the biological equipment needed for live birth.

The two genes--HoxA-11 and HoxA-13--make transcription factors, proteins that bind to other genes and tell them when to turn on or off. Like other members of the expansive Hox family of transcription factors, HoxA-11 and HoxA-13 control development of the basic body plan; they're also expressed in the uterus and related tissues. The sequence of Hox genes is so consistent across species that biologists once thought that the genes had changed very little through the course of evolution. The new study, like others in recent years, suggests that some divergence among Hox genes has in fact contributed to the diversity of animal body plans.

To investigate the history of HoxA-11 and HoxA-13, evolutionary biologist Vincent Lynch of Yale University and his colleagues examined the genes' sequences in a variety of animals, including frog, chicken, platypus, opossum, mouse, and human. They then reconstructed the sequences that likely existed in these animals' ancestors and used a standard technique to determine whether differences in the sequence likely arose by chance or by natural selection. Natural selection was responsible for changes in both genes in the common ancestor of today's marsupial and placental mammals, and for additional changes to HoxA-11 in the lineage that gave rise to placentals, the researchers report online this week in Proceedings of the Royal Society B.

This timing of the changes to the Hox genes parallels stages in the evolution of the mammalian female reproductive tract, as a primitive uterus and placenta first appeared in the common ancestor of marsupial and placental mammals and then became more elaborate in placental mammals, Lynch says. Lynch hypothesizes that the changes to HoxA-11 and HoxA-13 could have altered development, perhaps by allowing them to bind to genes involved in creating different kinds of cells.

The paper is the first to link the natural selection of developmental genes to a specific change in the way animals develop, the authors say. "It's a really interesting and suggestive correlation," says developmental biologist Matthew Ronshaugen of the University of California, Berkeley. These genes could have "played a major role in the evolution of the mammalian female reproductive tract," Ronshaugen says.

Related sites
Hox genes in vertebrates
The Female Reproductive System
Marsupial Mammals
Mammalian Development

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