This blog is the fifth piece in a series by Darrel Falk and David Kerk. The previous entry is found here.
In our previous essay, we discussed how, if evolution is true, we would expect that the embryonic development of complex structures such as the heart and its great vessels would proceed through a process of “adding new features on top of old.” Rather than each type of organism possessing a “direct development” where a particular complex structure is produced in the most straightforward way imaginable, things are interestingly complex. Within the embryo, development occurs in a rather roundabout way and includes intermediate stages from previous ancestral organisms. If biologists are interpreting this correctly, then we would expect that descendant species are building upon the genetic instructions of their ancestors. Gradually, through the eons of time, species alter these instructions enabling them to make new models of old “equipment.” So, just as we seestructural evidence for “adding new features on top of old” so also we would expect to seegenetic evidence of the same phenomenon.
The total collection of an organism’s genes (the genome) is, in essence, the instruction book on how to build its body. Furthermore, one can think of the instruction book as having chapters—like a “how-to-build-the-heart” chapter. If we investigated the genes which are important in making a heart, the genes used in today’s organisms would be an elaboration of an old “how-to-to-build-a-heart” chapter from an early version of the instruction book, a chapter that has been under continual revision for hundreds of millions of years. We would be able to make predictions about what sort of traces would remain from those much earlier heart chapters, and we would be able to determine whether predicted traces really exist. In essence what we would predict is this: we would expect to see evidence for certain “old” genes still in use in a similar manner today compared to what would have been the case in the early days of heart “manufacture.” Just as the structure of the heart of mammalian embryos goes through stages where the developing heart almost certainly resembles the old heart of ancient organisms (see our previous post), so we would expect to see certain “old” genes still in use as the cells in the developing embryo “read” the heart chapter of the instruction book and proceed to assemble into a heart.
But what would be an example of an “old” gene, and how would it be possible to recognize one when we saw it? That’s our task, and we’ll begin it by reflecting on an old song.
I could stay young and chipper
And I'd lock it with a zipper,
If I only had a heart.
Who doesn’t remember this ditty from the classic film “The Wizard of Oz”? It’s the Tinman’s song, of course. What has this got to do with the development of the heart? Well, sometimes scientists can manifest a quirky sense of humor. Some years ago a gene was found in the fruit fly Drosophila which is very important in the development of the heart. If that gene is mutated, no heart develops. So the gene was named “tinman” because the poor mutant fly larva were constructed, just like the beloved character from the movie, without a heart.1
What sort of a gene is tinman? In essence, tinman is a master gene. It, like most genes, provides the instructions on how to make a protein. However, the protein product (named TINMAN) of the tinman gene is special. When produced in an embryo, TINMAN is able to activate the reading of other genes which carry the instructions on how to make a heart. Cells that receive the TINMAN signal start to follow the heart-making program and, as the process continues, the little embryo makes a heart.
The fruit fly heart is simple. It is little more than a muscular tube, but it has little valves called ostia through which body fluid can seep into the central core of the tube. By constricting, the heart pumps the fluid that accumulates inside of it by a process known as peristalsis. Peristalsis is a moving wave which constricts the tube at one end and then pushes the fluid forward just like you do with a tube of tooth paste. The moving constriction drives the fluid forward so that it leaves the open head end via the heart’s aorta ensuring ongoing circulation of the internal fluid in the insect’s body. This very simple heart is not unlike the human heart at its very earliest stage of embryonic development.
So how does the TINMAN protein cause embryonic cells to make a heart? The answer is pretty simple. In essence, the TINMAN protein just turns on a switch. As you sat down at your computer earlier today, you probably used your index finger to push the on-switch, correct? That’s what the TINMAN protein does. Just as your index finger opens up a series of circuits in your computer that eventually constructs an image on the monitor, TINMAN does the same in the Drosophila embryo. It turns a switch from “off” to “on.”
Let’s carry this analogy between the switch on your computer and the TINMAN switch in embryos further. Let’s say that as your computer begins to age you update it regularly. Maybe, the monitor starts to get out-of-date, for example, and you decide you want a new model, one with a nice wide screen. So you change the monitor. The old switch still works though and you still turn your computer on by pressing the button with your index finger. Let’s say that another year goes by and you want a new wireless keyboard, so you substitute that. The next year, it’s time for a new hard-drive so you add that as well. Indeed, as the years go by you find you’ve changed almost everything except the housing for the switch. Because you’ve built your computer bit by bit, it now bears very little resemblance to your old computer—it has evolved—but the switch is still the same and it still works with your index finger. It’s not a toggle switch; it’s not a foot switch nor is it a voice switch. It is still the same index finger switch and it works just fine.
Analogies are never perfect, but that one might help clarify an important point about the TINMAN switch for heart development. Let’s make a prediction about what would happen in the history of making new varieties of hearts if evolution is true. Evolution of the heart, by definition proceeds by making gradual single step changes to a pre-existing heart design. If ever the TINMAN switch was broken, what would happen to the organism? No heart, correct? Organisms with a broken switch would die. End of the lineage, correct? Would you expect a major overhaul in the switch, like changing it from a push-button to a voice-activated switch in a single step? No. If evolution were true, you would expect the switch to stay pretty much the same over the years. In some lineages, the switch might come to activate increasingly complex circuits, as increasingly sophisticated hearts are built to sustain increasingly complex bodies, but the initial “make-a-heart” switch ought, most likely, to remain a TINMAN switch. It does one thing (turns on a circuit), does that one thing well, so why change it?
We want to emphasize that it is very clear that any switch will do. Embryos have hundreds of switches each activating a particular embryonic circuit. The reason that we would expect switches to be conserved is not because one variety of switch works better than another, it is, quite simply, historical: once a switch is put in place, it is exceedingly unlikely that it will be changed.
So in the fruit fly, that which controls the “make-a-heart” switch is TINMAN. What controls the same switch in other organisms? The zebra fish is a little aquarium fish which produces transparent embryos. This transparency trait makes it the embryologist’s dream organism and thereby it has been widely studied. Fish, like fruit flies, have a heart. We talked about the structure of the fish heart in our last post. What controls the “make a heart” switch in zebra fish? You guessed it. Out of the hundreds of proteins that operate various switches in fish embryos, the one which controls the “make-a-heart” switch is almost the same as the fruit fly, TINMAN. In fact, when one puts one of the several zebra fish versions of TINMAN into mutant fruitfly embryos which lack their own TINMAN, one of the zebra fish versions will throw the switch, and cause the mutant embryo to produce a heart.2 Zebra fish and fruit flies have been on separate lineages for over 500 million years, however each, despite hundreds of possible switches, still retain a switch that can only be activated by a variety of the TINMAN protein. So do other organisms like frogs and mammals have this same switch operated in the same way? Yes, all tested vertebrates, including humans make their heart in response to the TINMAN signal. It has changed a little more in mammals so the mammalian varieties are not interchangeable with the fruit fly’s TINMAN, but it is still the same gene which makes almost the same protein.
This is exactly what one would expect if evolution is true and it is one of a host of verifications for the fact that creation occurs through gradual modification of pre-existing organisms. Any switch would do if organisms were being created from scratch. A switch is a switch is a switch. All that is needed is to start the “make-a-heart” program. If evolution is true, one would expect that frequently the same switch would be used down through the eons of time. Furthermore, one would predict there would, through time, be some slight mutational modifications. This is exactly what we find, and we find the same exact sort of pattern for the other switches which activate the embryonic construction of other body structures, like the eye, the limbs, and the vertebra for example.
Five hundred and fifty million years ago the hearts of the entire animal world were simple tubular hearts, something that still characterizes heart development at the early embryonic stages in animals today. However, as time went by in certain lineages the hearts became increasingly sophisticated. As they became more sophisticated, new switches for the add-ons were put into place. In our next post, we’ll look at some of the new switches and explore some predictions we can make about them as well.
1. Bodmer, Rolf, (1993). “The gene tinman is required for specification of the heart and visceral muscles inDrosophila” Development 118: 719-721
2. Park, Marjon et al (1998). “Differential rescue of visceral and cardiac defects in Drosophila by vertebratetinman-related genes.” Proceedings of the National Academy of Sciences 95:9366-9371.
For more general reading on this topic, we recommend:
Sean B. Carroll, Benjamin Prud’homme and Nicolas Gompel (2008). “Regulating Evolution.” Scientific American. (May, 2008 pp. 61-68.)
Caroll, Sean B. (2006). Endless Forms Most Beautiful: The New Science of Evo Devo and the Making of the Animal Kingdom