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Tracing the origins of that ‘most intimate of structures’

by Rowan Hooper

Former Colorado congresswoman Pat Schroeder once quipped: “I have a brain and a uterus and I use both.” The former is what separates humans from other mammals; the latter is what separates mammals from everything else.

Although mammals number only some 4,300 species (not much in the grand scheme of things), we’ve done pretty well for ourselves. We might not be as numerous as other animals, but without getting too self-congratulatory, we’re by most measures the most adaptable and certainly the dominant class of animal on the planet.

Arguably, we owe it all to the uterus. It’s our defining characteristic. Other animals have to lay eggs, but we mammals nurture our offspring internally until they are well developed. It’s perhaps the most intimate of structures produced by natural selection. But how did it evolve?

The most primitive of the mammals, such as the duck-billed platypus of Australia, actually lay eggs (they scrape into the classification because of other mammalian characteristics) and have very different reproductive systems to the more familiar animals that give birth to live young.

These mammals (marsupials such as kangaroos and placental mammals such as humans) don’t grow an eggshell around their developing young, but instead grow and feed them in a uterus. They are known as therian mammals.

About 180 million years ago, something happened to trigger the evolution from egg-laying to fetus-nurturing.

Here’s Vincent Lynch, of the department of ecology and evolutionary biology at Yale University, reflecting on that “something”: “Probably eggs were kept in the reproductive tract for longer and longer periods of time. At some point the shell was lost and this provided that embryo with a great advantage because now it did not have to rely on the yolk for all of its nutrition, it could get it from mom’s uterus.”

As soon as that happened, the evolutionary floodgates opened. The origin of the uterus was one of the most dramatic advances in vertebrate evolution.

“Once the embryo started to demand nutrients from mom, any adaptations that aided nutrient exchange, like the placenta and the embryo implanting directly into the wall of the uterus, would be very advantageous,” said Lynch.

It’s fairly easy to come up with plausible reasons for the evolution of a particular trait, but since the relevant selection pressures that led to the uterus occurred so many millions of years ago, we will always be guessing. What we need is some sort of solid evidence, a record of what happened. And this is exactly what Lynch and colleagues have now got.

How could a record survive 180 million years? Easy — in something that has been passed from generation to generation, from ancestral mammals all the way to you and me. In other words, our genes. Remarkably, evidence of the evolution of the uterus is still visible and measurable in mammalian DNA.

Lynch and colleagues looked at the genes that control the development of the female reproductive system from a variety of animals, including human, opossum, platypus and frog. Mammals that give birth to live young have very different reproductive systems to egg-layers, so the researchers reasoned that there would be a difference in the relevant genes. Sure enough, they found evidence for two bursts of rapid evolution. The first happened when the therian mammals split away from the egg-layers, and the second when the placental mammals split from the marsupials.

“Luckily, changes in genes occur in more or less clockwork fashion,” said Lynch, whose work was published last week in the journal Proceedings of the Royal Society. “Much like a metronome ticking away, changes accumulate, so you can estimate how many changes there should be and then compare that to how many changes there actually are. In the ancestral therian there were far more changes than expected. This is the rapid burst of evolution.”

The researchers looked at Hox genes, a family of managerial genes that orchestrate development. Hox genes tell cells in a developing embryo what their role is. Four of the Hox genes are involved in the development of the female reproductive tract, directing cells to form fallopian tubes, the uterus or the vagina.

“Hox genes are lined up tightly along the chromosome,” said Lynch. “The first gene in the row is turned on earliest, and in the most anterior part of the organ, the second gene in the row is turned on a little after the first and further down the organ, and so on. In this way, each cell knows whether they are near the head or the middle or tail and how far along in development they are.”

If it seems amazing that we can still read in genes the changes that occurred in our mammalian ancestors 180 million years ago, try getting your head round this: Similar bursts of evolution can be read in genes shared by plants and animals. And those two groups of organisms started evolving separately some 1.6 billion years ago. If only Darwin could have seen such evidence for natural selection, 100-odd years ago . . . and if only those who preach the nonsense of creationism and intelligent design could, today.