When is similarity homology?
In my last post, I mentioned that two proteins with a sufficiently similar sequence are considered, in many cases, to be homologous—that is, they are derived from the same common ancestor in natural history. Josh had a really good question: why should we assume that sequence homology in molecular biology is evidence for common descent? A designer could just as easily have made organisms filled with genes that are similar in sequence. However, by looking at the divergence of sequence alignments, we can construct family trees that fit to an evolutionary model of natural history that explains the data without the need for a designer and which offers extraordinary predictive power. Any fact from nature that deviates from these predictions would be very strong evidence against an evolutionary model and against the theory of common descent: but no such falsifying evidence has been found. This is an important difference between creationism and evolutionary science. There are many lines of evidence that could refute the theories of evolutionary biology instantly: yes, fossil rabbits in the Precambrian is one famous example that Richard Dawkins often cites (this was originally said by J.B.S. Haldane). But a lot of molecular evidence from the genome sequences of various plants and animals exists which fit perfectly into the predictions made by evolutionary theory.
For example, all the primates have a degree of similarity in the sequences of certain genes that differs from the sequences of the same genes from birds. If a primate-like myoglobin was found in a finch, this would go against the prediction of the family tree. But this just isn’t the case in the real world. Even more convincingly, there are long sequences from the genomes of all eukaryotes that do not code for any proteins. Changes in these sequences are therefore not subject to natural selection and are completely neutral. Changes in these sequences are therefore a good measure of random genetic drift. It is with such sequences that molecular clocks have been constructed which allow us to date certain points in the family trees that we make. These methods allow us to predict exactly when certain families diverged from others in evolutionary history. And, in fact, these predictions line up exactly with what is found in the fossil record. Given that random genetic mutations occur at a certain rate, we can compare the non-coding sequences of a bird with the non-coding sequences of a mammal. What we find is that the common ancestor of birds and mammals existed about 300 million years ago. When we look at the fossil record and we look at strata that were laid down 300 million years ago (as measured by various other geological clocks), we see neither birds nor primates—nor even mammals or dinosaurs at that point in geological history. We only see the reptile-like animals that were the common ancestors of modern reptiles, dinosaurs, birds, and mammals (including primates).
What about these mathematical methods? When we compare two sequences, we want to know whether they are homologous. This is a fundamental task in bioinformatics, evolutionary biology (tree-making), and even structural biology. Sequence alignment methods must not only align the sequences, but be able to compare alternative alignments to provide an assessment of their significance. The aim of an alignment score is to measure the degree of similarity between the sequences and be able to distinguish among the many alignments that can be generated between two sequences allowing for gaps. One plausible way to score an alignment would be to measure the number of nucleotide changes required to convert one amino acid to another. However, evolutionary selection usually occurs at the level of protein function and this biases the mutations that are accepted in a way that simple chemical substitution algorithms don’t account for. The goal of scoring is therefore usually to measure the likelihood of a common evolutionary ancestor.
Two mechanisms could give rise to differences in protein sequences: a random model and a nonrandom (evolutionary) model. In the random model, there are no structural or functional processes that place constraints on the sequence to cause similarities, and there is no family relationship between two sequences. All sequences can be random selections from a pool of residues. If the proportion of an amino acid a in the pool of residues is Xa, this fraction will be reproduced in the amino acid composition of the protein.
The non-random model proposes that the sequences are evolved from a common ancestor sequence which, over the course of intervening years, diverged into two different sequences. Therefore, the identical residues in each sequence are identical because they were conserved in the process of evolutionary descent, while the different residues either caused no change in the function of the protein or were involved in the creation of a new function which contributed to the survival of the organism descended from the common ancestor. There is now a high correlation between aligned residues. The probability of occurrence of particular residues depends not on the pool of available residues, but on the residue at the equivalent position in the sequence of common ancestor. In this evolutionary model, the probability for finding a particular pair of residues is Ya,b. Critically for the debate between creationists and evolutionary scientists, the similar sequences don’t exist because they are the best sequence for building a protein suited for a given purpose, but because they are derived from a common ancestor. Therefore, one gene product may perform one biological function in one organism, and perform a different function in the organism’s cousin. But they each bear the stamp of their common ancestry—biological inheritance is the raw material that life has to work with to go about the business of survival. In a created world, all proteins with different functions would be unique—they would not have large stretches of homologous sequence derived form their common ancestry. An important example of this is the case of myoglobin and hemoglobin. These proteins have slightly different sequences but very different functions. An examination of their sequences shows that they are unmistakably similar, although a designer would have simply built two unique proteins from the ground up. This lack of robust design is also betrayed by the fact that very small changes in the sequence of hemoglobin can have catastrophic consequences for the organism—it is extremely fine-tuned to in terms of the relationship between its sequence, its structure, and its function.
Assume that in a single position in an amino acid sequence alignment that two residues a and b are aligned. Because the evolutionary model assigns the probability of finding particular pairs of amino acids rather than individual probabilities for given amino acids, it would give a probability of Ya,b, while the random model would give a probability of this occurrence as XaXb (a product, since the two residues occur independently of one another). The two models are then compared by taking the ratios of the probabilities: Ya,b /XaXb. This is the odds ratio, an important value in bioinformatics. If the ratio is greater than 1, the nonrandom model is more likely to have produced the alignment of these residues. This process is done for every pair in the alignment to determine whether the sequences are likely to have been derived from a common ancestor or not. Ultimately, through the use of the log-odds ratio and substitution matrices (and I won’t go into the math unless you want me to in the comments, but see this Wikipedia article), we can score alignments to determine the probability that similar residues line up by chance or through some evolutionary process.
Ultimately, these mathematical methods have been very powerful tools in reconstructing evolutionary relationships in the form of phylogenetic trees. We can align, for example, the hemoglobin sequence from every animal we can find, and construct a phylogenetic tree that gives us a model of the evolutionary history of every animal on earth. Here is the amazing part: the phylogenetic tree for every gene gives the same result. In addition, the model of evolutionary history of a given set of animals constructed from sequence alignments also explains speciation events that correlate perfectly with the geographical distribution of descendants of a posited common ancestor (which, in many cases, can be directly observed in the right place at the right time in the fossil record).
So, sure, it is not logically necessary for two similar structures to be the result of common descent from a shared ancestor. But Darwin’s powerful intellectual contribution was to assume that this was the case, and then work out the consequences. The amount of data explained by this assumption and the number of predictions that the theory yields is so vast that it has been our greatest tool in our quest to understand life on this planet. The other theory, that an alien intelligence rigged the game, has so far been an intellectual dead-end. My next post will be a piece on the molecular clock.
9 Responses to “When is similarity homology?”
Thanks for clarifying a point raised in your last post. For me the differences between similarity and homology were not instantly obvious.
Interesting post. A couple of comments…
There are many lines of evidence that could refute the theories of evolutionary biology instantly…
It is worth noting, however, that if such evidence were found, biologists would not conclude that creationism must be true. They would attempt to find some natural mechanism to explain the evidence–first within the evolutionary framework and failing that, a new theory to replace evolution.
This is not because biologists are obstinate theophobes, but because creationism does not make a useful scientific model. Creationism makes no predictions, because a God who is capable of working outside of the laws of nature is not predictable.
In a created world, all proteins with different functions would be unique.
Not necessarily. As I discussed in the comments to your previous post, that assumes the creator’s intent was to create the most optimally-engineered design imaginable. Yet, the Bible implies that God is not merely the ultimate engineer, God is also the ultimate artist.
I don’t see why the ideas are mutually exclusive. Why couldn’t God have created the natural world through evolution? What interests me is that things were able to evolve to the point where an intelligent, self-aware species came to be. I’ve often heard that if subatomic forces were just slightly different, the building of long carbon chains would be impossible, thus rendering impossible the formation of complex molecular structures that enable life. That conditions were just right for this and other developments was either an extraordinarily happy accident, or a result of divine intent.
You’ll note, Mike, that no where in my post do I argue against the existence of God. The evolution of biological species is simply a process that takes place in nature. I’m sure that if God is somehow behind the existence of the universe, He knew that this process would unfold as it did. I just don’t really think it’s relevant to the actual mechanisms by which living systems have evolved in time on Earth. The urge to somehow inject God into biology is simply strange to me. If you believe in God, then God is of course ultimately responsible for everything – and you should have no problem with evolutionary science. We look at the atmosphere of Venus, and we know that its composition and thickness along with that planet’s proximity to the sun is the reason why Venus is so hot on its surface. But no one says, “God made Venus really hot through a runaway greenhouse effect.” But, yes, I agree with you that if you believe that God created the universe, then he is certainly responsible for creating a universe with physical conditions conducive to the eventual formation of the planet Earth, and is responsible for the process of biological evolution through natural selection on that planet. But God is also responsible for everything else in every microscopic corner of the vast universe in that situation, and I just don’t see how it’s relevant to science.
Hi Eric,
Thanks for your comment. It’s true that scientists wouldn’t necessarily search for a designer if fossil rabbits were found in the Precambrian, for example. But it would certainly cast tremendous doubt on the entire structure of evolutionary biology as it currently stands. And if sequence alignments didn’t give us ordered family trees, but instead showed a tree resembling a tangle of wires, it would cast doubt on common descent. A lot of scientists would be forced to conclude that living things have been placed here by something externally. I just honestly can’t think of a natural explanation that would explain such data. They might not conclude that the designer is God, but the designer would certainly be a thrown around in a lot of theories.
As for God as an artist rather than as an engineer, it is of course true that I cannot pretend to assign any motives to the possible designer. But that is also precisely why creationism is such poor science – which I think you agree with.
Mike,
What you have proposed is known as theistic evolution, and there is a lot of writing and discussion out there on the subject.
Chuck,
I wouldn’t say that creationism is poor science; I would say that it is *not* science. There’s no useful scientific model based on creationism; as I said, it makes no predictions because God is not predictable.
That’s not to say that creationism has no value, which is what the likes of PZ Myers and Richard Dawkins and their followers imply when they say it is not science. Ethics is not science, but it is an important intellectual endeavor nonetheless.
More and more, it is becoming my opinion that science is above all a practical pursuit. It is the way we discover how the natural world works. Questions about the meaning of life, how one should live their life, etc. are extremely important, but cannot be answered by science. (This seems glaringly obvious as I write it, yet this perspective is often lost in contemporary debates such as “evolution vs. creationism”, etc.)
Eric,
Going through an evolutionary biology program for grad school actually made me think, for a long time, about this part of your comment:
“Questions about the meaning of life, how one should live their life, etc. are extremely important, but cannot be answered by science.”
I’ve increasingly adopted the view that this is not quite true, specifically because of details of the biological evolution of humans that have been coming to light, and how that information changes what we know regarding our behavioral motivations. It has spawned a field known as evolutionary psychology. I will not say that it can ‘answer’ questions about how to live, but it has definitely made some contributions toward how we should think about our actions, and how we should change our judgment of the behavior of others. This can be a ticklish subject because people often have a difficult time approaching it with emotional neutrality, but I’ll put it out there anyway.
A guy named Randy Thornhill made a name for himself in the 90s by conducting behavioral studies on controlled groups of human subjects. (Feminists hated him, so he was more infamous than famous, but that is just another example of people shooting the messenger- the data say what they say.) One of his hypotheses was that otherwise impractical female human secondary sexual features, specifically enlarged mammaries, are the result of selection- but of an interesting kind. He suspected that mammaries in female humans serve as a trait that males subconsciously (and rapidly) assess for symmetry, which serves in turn as an honest indicator of genetic health. That developmental symmetry serves as an indicator of genetic quality had already been thoroughly determined through population studies on other organisms. (Only very recently in history could we alter breasts artificially, so we’ve had a few million years for the trait to honestly serve as a mate choice cue and thus for the assessment behavior to become entrenched in the male program.) He did a carefully controlled study in which men were asked to rate attractiveness of photographed sets of breasts on a numerical scale (nothing else about the female subject was visible, so no facial or other body cues). The outcome was more interesting than one might suspect. It turns out that larger breasts received both the most positive and most negative ratings, while the relative neutrality of scores increased as size of breasts decreased. This is exactly the pattern that one would predict if size were serving to enhance evaluation of symmetry. Size versus asymmetry of the breasts could be objectively measured and compared with the descriptive statistics of their scores. The primary determinant of whether a score was positive did in fact turn out to be symmetry, with size having more to do with the strength of response.
This is important for a few reasons, both social and philosophical. First, some background from evolutionary behavior. Developmental symmetry cues as surrogate indicators of genetic quality have been shown to operate in other animals, with separate sexes, that have to engage in mate choice strategies. These cues have strong genetic components. What has been less easy to study, but not impossible, is that the strength of the assessment behavior is in some cases also related to quality of offspring. In other words, the degree to which the _observer_ pays attention to the cue is as important as the value of the cue itself. If you mate indiscriminately, the average genetic quality of your offspring is lower. (A lesson that warrants repeating in this town, but nevermind…) This means, then, that it is highly likely that the male human’s nearly subconscious habit of “the glance” is a piece of firmware that is rooted way deep down in the part of the program that exists because of strong selection for good mate choice habits. Okay- sorry, here is the social/philosophical point. Until now, this area of behavior has been treated strictly as a moral/ethical issue. We all know that the heightened sensitivity of males to breast size is responsible for much of what is considered ‘wrong’ with advertising, clothes, etc. However, when this is discussed, the conversation rarely gets further than the opinion that men should somehow feel ‘bad’ for this. We are somehow morally at fault, and should be more sensitive to the plight of the objectified woman. Well… while it is understandable that some women may be insecure about the phenomenon, I must respectfully call bullshit. Men are doing EXACTLY what they are supposed to do. The overpowering drive to visually, rapidly assess female shape (literally in milliseconds) is there for a very, very good reason. Knowing this, I think it is time to ask an important question. How should this change some of the conversations that we have with our children? Should we continue to couch behavioral teaching in a strictly moral framework in which mistakes are cause for emotional judgement, or should we start switching over to something like this:
“Look, there is a lot of old, leftover programming in your head, put there by a very long period during which certain strategies were what made people successful in life. This may cause you to want to do things that aren’t always socially acceptable. Do no feel ‘bad’ that it is there- it is supposed to be there, and there is nothing that you can do about that. It is, however, your responsibility to be _aware_ of that, and to consciously manage it. It is your _responsibility_ to be aware of how you operate and watch out for the pitfalls that it can cause, but not your _obligation_ to feel ashamed that that is how your brain works. Just keep an eye on it and make sure it doesn’t get you into trouble.”
That would have made much more sense to me when I was a kid. Both my parents’ religious take on the matter and the feminist responses to the same issues seemed monstrously unfair. It was clear by the time I was in high school that there was some wiring under the board that no one was talking about- probably because no one knew any better. Now, thanks to the efforts of people like Randy Thornhill and Bob Trivers (the parental investment theory guy) we have more specific knowledge, of how biology interacts with social behavior, to use when teaching kids how to think about themselves. In that way, turning the lens of science on ourselves can actually make some of those questions about life a little easier understand.
Chuck,
I agree with you that the progress of biological research is in no way dependent on whether or not there is a god behind it all. However, I disagree in part to your assertion that God is irrelevant because much of the teaching of evolution falls into using terms like “accident” and “chance” (as in the results of evolution are purely chance and accidental) that not only go beyond the boundaries of scientific research but are in fact at odds with the idea that God might be behind everything. I think if you were to investigate biology textbooks you would find much language that is not strictly limited to the findings of scientific method and that ventures into the territory of metaphysical claims, usually with the purpose of denying them (I remember how the 4th ed. of Neil Campbell’s biology textbook that I had in college attacked the idea that humans have a soul). So I think a line has already been crossed, and a bias is present.
I also think that when you are dealing with junior high and high school students many of them are not at the level of development where they can separate ideas about the development of life that reside strictly in the sphere of what can be researched from ideas venturing into the metaphysical sphere. Thus I think it would be useful for textbooks to make the exact clarification you did – that simply accepting the theory that life has evolved neither endorses nor excludes the idea that a metaphysical being might be behind it.
If God created a universe governed by statistical laws (and if He created the universe, then He did indeed create one governed by statistical laws), then something can happen both by “chance” and by His will. Also, biologists rarely use the word “accident” do describe anything in nature, and especially in living systems. Rates of DNA mutation have an element of statisical chance incorporated into them, but even these mutation events are not “uncaused” in the sense that the word “accident” implies. It’s just that the rate of mutation is caused by many different things. Also, when biology textbooks say that humans have no soul, what they are doing is attacking the concept of vitalism. Campbell spoke from a lack of knowledge of all the various concepts of soul out there if he really said that humans have no soul. The Aristotelian model of the soul does not require vitalism. It is the “form” of the body – the arrange of matter in space that makes the body the body. I believe (and correct me if I am wrong) that this concept is consistent with Christianity, or at least Catholicism. The resurrection of the dead is required at judgement day because the body cannot be distinguished from the soul – the soul is the form of the body.
But what distinguishes living matter from dead is not some mystical energy field that somehow (inexplicably) interacts with matter. What distingishes dead matter from living matter is that living systems are in a state of enegetic non-equilibrium at the level of chemical reactions taking place in every cell. Energy enters in the form of food, is utilized in chemical reactions in the process of metabolism, and is dissipated in the form of heat. When equilibrium is reached – usually because the fuel supply (food or oxygen) is cut off, or because anatomic, cellular, or molecular architecture that makes the process possible breaks down in some way – then the organism dies and begins to resemble inanimate matter.
I do maintain that metaphysics plays almost no role at all in all of this. But religious people would do as well to keep their metaphysics out of science as scientific people would do to keep their science out of metaphysics. The two simply have nothing to do with one another.