Evolution on steroids: Chance ruled in building an estrogen receptor

Enlarge / The estrogen receptor, bound to a steroid. (credit: PDB)

Studying alternate realities has traditionally been the purview of physicists, cosmologists, and philosophers. Maybe theologians. But at the University of Chicago, biochemists, molecular biologists, and geneticists in Joseph Thornton's lab are examining why things in biology have turned out as they have and not some other way. They note that "history leaves no trace of the roads it did not take" and ask: is the current state of things inevitable?

And, if it's not, it's worth figuring out why things aren't different-and whether the outcome could have been better than the solution life on Earth ended up with.

Remaking the past

By "things" here I mean proteins. For Thornton's lab, this means the estrogen receptor and a related receptor that handles other steroid hormones like androgens, progestogens, and corticosteroids. These receptors bind their preferred steroid, then bind to specific DNA sequences and control the activity of a particular suite of genes. The DNA sequence that the estrogen receptor binds-called the estrogen response element-differs from the DNA sequence that the more generic steroid receptor sticks to, though only in two locations.

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