Evolution 101

Saturday, March 25, 2006

Molecular Evidence 1: Protein Functional Redundancy

All right, this is the first podcast in a series of six that I’ve planned on the molecular evidence for evolution. I’ll be using Dr. Douglas Theobald’s resource on Talk.Origins.org pretty heavily, so you can follow along with me there if you like.

The first piece of evidence is protein functional redundancy.

Proteins are, as a group, completely essential for life’s function, but there are some proteins that are more essential than others. These proteins perform very basic but essential tasks that all organisms require for life. We can call these proteins, “Ubiquitous Proteins.” These ubiquitous proteins are completely independent of an organism’s specific function or ecological niche- all organisms from bacteria to humans have these proteins, and they do the same thing no matter where they’re found.

Now, if you remember the previous podcast, the Molecular Biology Primer, you remember me talking about the relationship between protein structure and function. I didn’t get into much detail last time, but I’ll expand on it a bit more here, because it’s a pretty crucial concept for this piece of evidence. The function of a protein is determined by its structure. Imagine that we have an enzyme, which is a chemically active protein, that has the function of cutting other proteins in half. To create a conceptual model in your mind, imagine that the protein is basically like a pair of scissors. The function of a pair of scissors, to cut things, is determined by its structure, which is essentially two blades and a fulcrum, or pivot point. A pair of scissors has a pretty basic structure AND function, and so it’s not too hard to make different variations on the basic structure without changing the function too much. For example, you can make the scissors out of steel, iron, brass, or even plastic. You can make the handles longer, or shorter. You can make the blade longer or shorter. You can even have left-handed, versus right-handed scissors. So it’s pretty safe to say, if you want to cut something, you have a pretty wide variety of choices if you need a pair of scissors.

In the same way that you can vary the way you make a pair of scissors without giving up its basic function, you can vary the way you make a protein without giving up its basic function. Remember, a protein is made by constructing a long chain of amino acids, and each amino acid is distinguished from the others because of its unique side chain. That makes each amino acid slightly different from all the others both chemically and physically. Some amino acids are large, some are small, some are electrically charged, some are not, some attract water, and some repel water. Depending on specific interactions between different amino acids in the chain, the protein will twist around itself and fold up in a very specific structure. Now comes the tricky part- you can get two very similar structures from two very different chains of amino acids. To help you follow along with me, try out another conceptual model- imagine that a protein, instead of being constructed from amino acids, is constructed from Legos. (I hope I’m not violating any copyright here) Maybe I should say “small plastic construction blocks that are similar to Legos.” Whatever. Anyway, let’s say that you have a huge box of Legos, but the whole box only containes 20 different pieces. If I ask you to build me a pair of scissors out of Legos, how many ways do you think you could put the pieces together to get a decent Lego model of scissors? I haven’t actually tried this, but you could probably get pretty many, right? Probably a whole bunch. OK, well, in the same way that you can use many different combinations of Legos to give the same endproduct, you can use many different combinations of amino acids to give the same basic protein function. A more technical way of saying this is that for any given protein, there are many different amino acid sequences that are functionally redundant.

OK, this is all well and good, but what does it mean in terms of evidence for evolution? Well, you remember that I started by talking about Ubiquitous Proteins. These are proteins that are so essential to the basic functions of life that they can be found in every living organism. That is to say, their function is absolutely necessary, and what did we just learn about function? It can be produced from many different combinations of amino acids. So ubiquitous proteins are also functionally redundant in terms of amino acid sequence.

Now, before we look at the evidence, it behooves us to come up with hypotheses. This is part of the scientific method, and very essential. Without a hypothesis, we can’t draw meaningful conclusions- we’re just making observations. Now, we need to have two hypotheses- an evolutionary hypothesis and a null hypothesis. If the data support the evolutionary hypothesis, then we can conclude that evolution is the best explanation for the data. However, if the data support the null hypothesis, then we can conclude that evolution is not the best explanation for the data.

The null hypothesis posits that the evidence will show that amino acid sequences of ubiquitous genes will not be highly similar between any two given organisms. We know that the null hypothesis is possible because of the nature of protein function to be caused by many, many different variant amino acid sequences- that for any given protein, there are many amino acid sequences that are functionally redundant. Thus, since there are so many possible amino acid sequences for any given ubiquitous protein, there is no reason why each organism could not have a completely different amino acid sequence for any given ubiquitous protein. But, let’s say that the null hypothesis isn’t true- what other phenomenon could the evidence show? Well, if the evolutionary hypothesis is true, then different organisms are related to each other by heredity. Since, as I’ve mentioned before, the only mechanism which has been shown to result in similar sequences between organisms is heredity, the evolutionary hypothesis posits that the evidence will show that amino acid sequences of ubiquitous genes will be highly similar between different organisms.

So, let me just go over those two hypotheses one more time before we look at the evidence. If evolution is not true, then we would expect to see that the amino acid sequence of a ubiquitous protein would be completely different in different organisms. If evolution is true, however, then we would expect to see that the amino acid sequence of an ubiquitous protein would be more similar between organisms that are closely related. And the more similar the sequence, the closer the hereditary relationship. OK, let’s look at the data.

Cytochrome C is a ubiquitous gene that is found in all organisms, including animals, plants, and bacteria. It’s an essential gene for cellular metabolism, and helps to provide energy for all life processes. Cytochrome C fulfills the prediction of ubiquitous proteins- that is, it is extremely functionally redundant. Many different amino acid sequences have been shown to fold up into the basic structure required for Cytochrome C function, and in fact among bacterial strains, completely different amino acid sequences are redundantly functional. Experiments in yeast show that if you remove the yeast’s own Cytochrome C protein, you can replace it with Cytochrome C from humans, rats, pigeons, or even fruit flies, and it works fine. A study was published that shows there are, in fact, over 10^93 different possible amino acid sequences for Cytochrome C. That’s more possible sequences then there are atoms in the Universe. So, Cytochrome C is very functionally redundant, and it would be possible for every single different organism to have a completely different amino acid sequence, if evolution is not true.

So what do the sequence comparisons show? Let’s compare humans and chimpanzees. If evolution is true, then chimpanzees are our closest relative, but if evolution is not true, we’re no more related to chimps then we are to crickets. But if you compare the amino acid sequence of humans and chimpanzees, you see that they are exactly the same. Exactly the same. And when you compare human Cytochrome C to that of other mammals, you find that there is only about 10 amino acids difference between them. The chance of this happening without shared heredity is about 1 in 10^29. If you compare human Cytochrome C with the organism the least related to us, outside of bacteria, you find that there’s only about 51 amino acids difference between us. The chance of this happening without shared heredity is about 1 in 10^25.

To review, protein functional redundancy is the phenomenon by which many different amino acid sequences can give the same function in any particular protein. This phenomenon means that closely similar amino acid sequences between organisms implies shared heredity. Examination of the amino acid sequence of a ubiquitous protein shows that different organisms have a greater sequence similarity than would be expected by chance, and thus supports the evolutionary hypothesis.

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