The History of a Clot

As remarkable as the antifreeze in notothenioids may seem–as tempted as some might be to call it Intelligently Designed–the evidence strongly suggests that gene duplications and less drastic mutations gradually created it. With these sorts of mutations, evolution can do even more: it can create entire systems of molecules that we depend on for our survival.

Consider the molecules that create blood clots. When we are healthy these molecules (called clotting factors) course through our blood, doing nothing. But if you should cut yourself with a knife and the blood in the ruptured vessels mingles with the surrounding tissues, that’s no longer the case. Some of the proteins in the tissue will react with one type of clotting factor and activate it. Now the clotting factor can start a chain reaction: it grabs a second type of clotting factor and activates it; it in turn activates a third type, and so on through a series of reactions. A final clotting factor slices apart a molecule called fibrinogen, turning it into a sticky substance that forms a clot. The complexity of the clotting system is its strength: a single original clotting factor can activate several factors in the next step, and these in turn can switch on many more factors in the third step. From a tiny trigger, millions of fibrinogen molecules can be activated.

It’s a remarkable system for stopping wounds, no doubt. And it depends on all its parts–if people are born without one type of clotting factor they become hemophiliacs, for whom a scratch may mean death. But that doesn’t mean that it had to have been Intelligently Designed.

Over the past three decades, Russell Doolittle of the University of California at San Diego has been testing a hypothesis for how blood clotting in vertebrates evolved. The fact that clotting factors can activate other clotting factors is nothing special; all animals have enzymes that activate proteins to make them ready to carry out many different kinds of jobs. One of these enzymes might be the ancestor of all the clotting factors.

Imagine an early vertebrate that lacked any clotting factor whatsoever. That actually isn’t so hard to picture, given that animals such as earthworms and starfish don’t have any either. They don’t bleed to death, because they have cells in their bloodstream that can become sticky and form crude clots. Now imagine that the gene for a slicing enzyme was duplicated. The extra copy evolved into a simple clotting factor made only in the bloodstream. It would be activated in a wound and slice apart proteins in the blood, some of which would turn out to be sticky. A clot would form, one that was superior to the old kind. If this initial clotting factor was duplicated, the chain reaction would double in length and become more sensitive. Add another factor, and it gets more sensitive still. Gradually the entire clotting process could have evolved this way.

Doolittle has put this hypothesis to the test and found support wherever he has looked. The clotting factors turn out to be very similar to one another, and Doolittle discovered they are all closely related to a digestive enzyme. Doolittle predicted that fibrinogen–the protein that clotting factors turn into a sticky, clot‑forming substance–descended from a protein in our invertebrate ancestors that did some other job. Doolittle looked for cousins of fibrinogen in our close invertebrate relatives and found one in the sea cucumber. Even though sea cucumbers can’t carry out a clotting cascade, they have a fibrinogen‑like protein in their bodies.

Testing these hypotheses hasn’t been easy. The tale of the antifreeze gene has required scientists to trawl for fish in iceberg‑choked oceans. The blood‑clotting story has required 30 years of lab work. They do not account for the evolution of cholesterol or of collagen, or of the hundreds of thousands of other molecules manufactured by life on Earth. Advocates of Intelligent Design make a great fuss over how little evolutionary biologists know about biochemical evolution. They take this ignorance as evidence that these molecules are too complex to submit to evolutionary explanations, and that Intelligent Design must be right. But all it demonstrates is that 50 years after the discovery of DNA, scientists still have plenty to learn about the history of life.