I've been getting swamped with links to this hot article, "Evolution reversed in mice," including one from my brother (hi, Mike!). It really is excellent and provocative and interesting work from Tvrdik and Capecchi, but the news slant is simply weird—they didn't take "a mouse back in time," nor did they "reverse evolution." They restored the regulatory state of one of the Hox genes to a condition like that found half a billion years ago, and got a viable mouse; it gives us information about the specializations that occurred in these genes after their duplication early in chordate history. I am rather amused at the photos the news stories are all running of a mutant mouse, as if it has become a primeval creature. It's two similar genes out of a few tens of thousands, operating in a modern mammal! The ancestral state the authors are studying would have been present in a fish in the Cambrian.
I can see where what they've actually accomplished is difficult to explain to a readership that doesn't even know what the Hox genes are. I've written an overview of Hox genes previously, so if you want to bone up real quick, go ahead; otherwise, though, I'll summarize the basics and tell you what the experiment really did.
First, to get through this, here's the minimum that you need to know. Hox genes are found in clusters, with the genes expressed colinearly—that means that the Hox gene at one end of the cluster is expressed at one end of the animal, the Hox gene at the other end is expressed at the other end of the animal, and the genes in between are expressed in a similarly orderly pattern that maps in sequence along the body of the animal. This paper only looks at Hox1, the anteriormost Hox gene, which is expressed far forward in the neural plate of the mouse, in cells that will contribute to anterior parts of the brain. You can forget about Hox2, Hox3, … Hox13 for now.
However, we do have to deal with multiple copies of Hox1. About half a billion years ago, there was a massive set of gene duplications in the vertebrate lineage—we have four clusters of Hox genes. Each of these four copies is designated by a letter, a-d. Hoxa1 is the first Hox gene in the first bank, Hoxa2 is the second Hox gene in the first bank, etc., and Hoxb1 is the first Hox gene in the second bank, and so on. This diagram will help you sort them out.
Again, though, for this paper we only care about Hox1, so we are only going to consider the four three copies at the left side of the diagram, Hoxa1, Hoxb1, Hoxc1, and Hoxd1. You may notice that there is no Hox1 gene in the c cluster; it was lost long ago, and no mammal has a copy any more. Furthermore, the Hoxd1 gene seems to have a negligible role in patterning the brain, so we can ignore it. This experiment is looking only at Hoxa1 and Hoxb1.
So: two paralogous genes, Hoxa1 and Hoxb1, expressed in similar regions at the anterior end of the nervous system, and conserved over half a billion years of evolution. They must do different jobs in development, or evolution would tolerate deletions of one or the other of the genes. What exactly are the specialized roles of these two genes?
We know that Hoxa1 is essential; delete it, and the hindbrain forms abnormally, with certain regions enlarged at the expense of others, disrupting the breathing centers of the brainstem, and you get a mouse that dies right after birth. The two genes also differ in protein sequence (they have 49% amino acid identity), and they also differ in significant ways in the timing and pattern of their expression in the brain. The difference in sequence suggests that Hoxa1 and Hoxb1 could have different functional roles, and the difference in how they are expressed suggests that they could be different in their regulation. Hey, this looks like a system where we can explore a big question in evo-devo: are changes in the coding sequence of proteins the most significant factor in evolution, or are changes in the non-coding regulatory regions more important? (Of course, we expect that both will be important, and there will be differing degrees of importance in different genes…but this is a case where we can directly compare these two paralogous genes and assess which differences are most important here.)
The experiment is simple to explain but tricky to do (the Capecchi lab, though, has developed some of the most amazing tools in molecular genetics): it's a gene swap. Pluck out the coding sequence for the Hoxa1 gene, and put it in place of the Hoxb1 gene, where it is surrounded by all the Hoxb1 regulatory elements. Also pluck out the Hoxb1 gene, and imbed it in place of Hoxa1. This means that Hoxa1 will be turned on at the times and places appropriate for Hoxb1, and vice versa. If the function of the coding sequences of these two genes are distinct and incapable of substituting for one another, we'd expect the resultant mouse to be thoroughly messed up.
The answer? The mutant mice are normal.
This means that as far as we can tell, the Hoxa1 and Hoxb1 proteins are functionally interchangeable. The differences that they've accumulated in the peptide sequence over that half billion years of evolution do not significantly change how either protein works, and all the important action must have taken place in the evolution of the regulatory control of each.
Let's take a look at the evolution of the regulation of these two genes. In the diagram below, the figure to the left illustrates the ancestral state, just after that ancient gene duplication. That distant gnathostome ancestor has four identical copies of the Hox1 genes, A1, B1, C1, and D1. They all also have the same regulatory elements, the chief of which are called ARE (the diamond) and RARE (the circle). RARE is the Retinoic Acid Regulatory Element—these genes are triggered to be expressed by retinoic acid. ARE is the Auto-Regulatory Element. Once the protein is expressed, it feeds back and binds to its own DNA, promoting the production of more copies of the gene.
The right side of the figure shows the changes that occurred in vertebrate evolution. The A1 gene has a regulatory specialization: it is more sensitive to retinoic acid (the larger RARE component), but is less sensitive to autoregulation (the smaller ARE diamond). The B1 gene has gone the other way, and while less sensitive to retinoic acid, is more strongly self-activated. C1 is gone altogether, and D1 is only weakly regulated. What you need to make a normal mouse is one gene that is readily activated by retinoic acid, which then binds to the ARE site of both Hoxa1 and Hoxb1, and another gene that is sustained by that autoregulatory activity. Lose either one, and you don't get the full dose and range of timings necessary for normal development; however, the system isn't too picky about which Hox1 gene is regulated by these two patterns.
The way they know this is by careful analysis of multiple kinds of gene swaps, and by studying mutant homozygotes and heterozygotes combined with deletions. Not all of the mice resulting from these experiments are happy; some are hypermorphs, where the Hox1 genes are too active, leading to reduced viability, while some are hypomorphs, where the genes aren't active enough, leading to deficient differentiation of nervous tissue and facial paralysis. They also identified a functional difference between Hoxa1 and Hoxb1 (they aren't completely interchangeable!): Hoxb1 is better at activating the autoregulatory region than is Hoxa1.
This wonderful diagram encapsulates all of these various experiments.
Start at the top, with the wild type animal. The normal sequence of events (simplified here) is that the retinoic acid signal turns on A1, which then switches on B1 via its autoregulatory element. B1 then strongly turns on its own ARE, producing a normal level of expression.
The second diagram is an experiment where the B1 peptide has been replaced with the A1 peptide. The initial sequence is the same, A1 is turned on by retinoic acid, and it switches on the ARE…but that produces an A1 protein, which doesn't autoregulate as well, so you get a weaker overall level of expression, and produce a partially paralyzed hypomorph.
The third experiment is the complement: this animal only makes B1 peptide. Retinoic acid turns it on, and it strongly activates the next protein, which also strongly turns itself on, and the combination of two strongly autoregulating agents leads to an overexpression of the Hox1 gene.
The fourth experiment is the double swap, with B1 in A1's place and A1 in B1's place. This produces an essentially normal animal, because it has the appropriate balance of one weak activator of autoregulation and one strong activator of autoregulation.
The last part of the diagram finally gets to the experiment that the news is making so much of, the reconstruction of the primitive state. The way the two Hox1 genes have specialized is that one has developed a robust RARE to make it sensitive to retinoic acid, and the other has a strong ARE to promote solid autoregulation. The ancestor before the gnathostome duplication event had only one Hox1 gene, but it would have had both regulatory components. So in this last experiment, they destroyed the B1 gene, and spliced the B1 ARE to A1, producing a hybrid single gene with both regulatory components. This situation also produces a normal mouse!
What the paper actually shows is not how to reverse evolution, but that the primitive chordate condition was to have a single, multifunctional gene, and that the result of a duplication event was a specialization of each copy to support separate subfunctions. What it also is is an example of is an increase in complexity, and the evolution of an irreducible system—one where each of two gene products is essential, and the animal dies without either—from one with a single generalized gene. While the research doesn't reverse evolution for an organism, it does turn back the clock on a single gene and show us key changes in its regulation.
Tvrdik P, Capecchi M. (2006) Reversal of hox1 gene subfunctionalization in the mouse. Dev Cell 11(2):239-50.
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How long before IDers declare another "major victory"?
Heck, I can even spin this one: The fact that Hox from a half billion years ago works as well as the current one in a mouse simply "proves" that mutations never "add any information" but only destroy it. Most likely, the old version works even better, and that's the healthiest mouse on the planet.
The above interpretation comes without even reading the article beyond a skim. Under the circumstances, I feel that this only adds to its authenticity. Expect a press release from DI real soon.
It is interesting to me because the Intelligent Design "theorist" Mike Behe once demanded that:
Behe assumed incorrectly it seems that this data could never be examined at this degree of detail.
Compliments on the post - you did a good job of explaining it to someone like me who has some science background (psych, neuroscience, plus my other interests), but isn't a scientist.
I'd LOVE to know more about the gene duplication explosion on the vertebrate lineage. I did not know about that until this very post.
I like your post. Thanks very much for an informative and readable (to a layperson) article. I am not a scientist, but I am extremely interested in learning more about science (although my passion is not so much biology but cosmology). My question (and this may betray my ignorance (and my potential bias because I am a Christian)) is whether or not there is any basis for determining what caused the original Hox1 gene to be replaced by two different genes, when the original Hox1 gene had both regulatory components? It doesn't seem that going from one gene that has both components to two genes that specialize in one of the components would be very efficient, unless there was a reason for the specialization. Again, I am NOT a troll, just a Christian lawyer trying to expand my understanding of a most difficult subject.
Thanks again for a terrific blog.
While I'm not a developmental biologist, I've been reading quite a bit of evolutionary stuff lately, so perhaps I can offer a few simple observations that might help.
First of all, I think there is a misconception in the second half of the question: the naturalistic explanation of evolution does not have any requirement that the result be "very efficient". Obviously, if some efficiency allows an organism to survive better, then that efficiency will be selected for, but for the most part, it's just a matter of what works.
Secondly, the "what caused" the Hox1 gene to duplicate was a mutation. Duplication is one of the possible mutations that can occur, and in this case, the mutation itself was neutral - it neither harmed nor benefited the original organism. There were simply two Hox1 genes, doing their work in all descendants of the mutant organism.
Finally, in some of those descendants, there were further mutations (probably widely scattered in time) in each of the copies of Hox1 that caused them to become Hoxa1 and Hoxb1. Any mutations that were so bad that they would have disabled the full function of both genes would have been selected against - the organism that had them would have died and not left any offspring. But mutations that disabled part of the function of one of the copies would not have been selected against if the function was still enabled in the second copy, and vice-versa.
It's complicated, and yes, inefficient. But there's no rule that says that life has to be efficient. It just has to work.
Thanks for the information. Very informative. I really appreciate the input.
Sweet. Not only is there an Intelligent Designer, but there's a Lazy Maintenance Guy.
"Crap, the Hoxa1 ARE just cut out. Well, we've still got the b1 ARE, I'll just pipe the a1 around to that. Turn b1 up a little more, crank up the a1 RARE, it'll be fine.
"What was that? You want me to replace the a1? Dude. Chill. The hindbrain is running fine. Besides, it's my lunch hour."
DP remarked
Owlmirror provided an excellent answer, but one aspect deserves emphasis: there is almost no reason for selection to favor efficiency. In fact, biological organisms are full of inefficient structures that no "intelligent" design manager would tolerate. Take, for example, the vagus nerve, a cranial nerve that connects the brain to the larynx. Due to a mis-communication between the designer responsible for the circulatory system and the one responsible for the nervous system (see Multiple Designers Theory) the vagus nerve loops around the aortic arch on the way from brain to larynx. That means it's substantially longer than required -- in the giraffe nearly 15 feet longer than required. Evolution by and large doesn't give a damn about efficiency. It is a satisficing algorithm (it finds good enough solutions given what it has to work with) rather than an optimizing algorithm.
Thanks for taking the time to explain it. It learned me good.
Posts like this are why this is the #1 science blog. Keep up the good work, PZ.
I want my evolutionarily-reversed mice to look like Tyrannosaurs, dammit! I want to see it bite off the heads of its white-coated creators! I'm completely disappointed.
Yes, but does swapping out the Hox genes create PYGMIES AND DWARFS?
I'd quibble with that a bit. That is, I think it would be fair to state that if some optimization provides some obvious advantage, then that optimization will be selected for. Obviously, what is actually "optimal" depends on the organisms' environment and resources, as well as the pre-existing genetic heritage.
An example that occurs to me is cave organisms that over time evolve into blind forms. As Carl Zimmer discusses here, that loss of ability can be seen as an optimization (that is, either as energy conservation, or as an improvement in feeding efficiency) in an environment where vision is not necessary.
But of course, that's not a developmental efficiency; it's a development to more efficiently exploit the available resources.
This dicussion raises an interesting point to stress with IDers: selection vs evolution. This is a clear distinction with scientists, but is easy to miss by the general population. Evolution is not a forward pressure. An organism does not evolve the ability to jump an extra foot (and say and get better food or find a better mate) because it is good for it or is more efficient. Evolution is just the random changes.
Selection sorts out whether that change is positive (can get access to more food or better mate) or is negative (makes the organism die or get less food or unable to mater). The negative change will not propogate long if it causes too many problems (the line will die out). If the change is dramatically positive, one could theorize the organism may be able to live longer, bread more, or otherwise increase in population faster than those that didn't have that change. If the change is nuetral, such as the case with Hox1 -> Hoxa1 and Hoxb1, it may be caried forward or it may not be (depends on mating and how it is resolved).
Separating selection and evolution for the non-scientists is a huge step that could help unmuddy the waters for some of the uninformed IDers.
Very good point, Chris. Thanks. That is a distinction that I, as a non-scientist, have never really heard articulated very well.
My concern is that there appears to be no answer, in science, for what causes the mutations in the first place. Christians can say "God caused them" and believe in natural selection (God set it in motion, and allows natural selection to take its course). That position doesn't really say much at all (either positively or negatively) about the science of the matter.
Huh? No. That simply isn't true. We teach about the mechanisms of mutation in undergraduate biology courses -- it's that basic. Take a look at Alberts' Molecular Biology of the Cell, for instance: it will tell you step by step how point mutations occur, duplications, etc.
DP: No mechanism for mutations?
Various chemicals and radiations have been classed as "mutagens" exactly because they're capable of changing a cell's genetic code. If a mutagen affects a germ line -- and if the number of changes is low enough that the cell can still function -- then those changes are heritable.
The precise mechanism of action varies from mutagen to mutagen, of course. But my understanding is that at least some mutagens have well-understood mechanisms.
Or am I misunderstanding your concern?
DP: My concern is that there appears to be no answer, in science, for what causes the mutations in the first place.
??? Mutations happen when DNA repair or replication goes wrong. I didn't think this was at all in doubt.
I guess the religious spin would be that these processes, being natural and not divine, are of course imperfect.
Here's the first article from a search of news.google.com for Capecchi, and it gets it right:
http://www.sltrib.com/utah/ci_4149640
Well, the exact cause of mutations can be a little tricky to explain.
Again, the naturalistic explanation is that there is chance variation at the biochemical level - while most reactions occur in a certain way, they don't always do so, because of differences in the environment that the chemistry is occuring (and I suppose it should also be pointed out that there is a universal background of radiation, some cosmic, and some from various minerals, which can effect the chemicals of life as well). Sometimes the result is neutral, but sometimes the chemical misfire is at such a critical point that the cascade of reactions resulting from that are radically different from what they normally would be.
In particular, some parts of biological systems having to do with reproduction actively engage in variation (I'm referring to meiosis here, which includes a point where chromosomes actively swap portions of themselves with other chromosomes). Again, this usually results in changes that are neutral, but sometimes the change is rather radical.
Now, we can suppose for a moment that some of this variation is (or was) "meant" to happen (because it resulted in the evolution of humans), but if so, it is a very inefficient process (to refer back to efficiency again). Quite often, the result of a mutation simply dies early in development, or is born horribly deformed, or is born looking normal but is sterile (so while the organism will survive, the mutated genes will not be passed down to the next generation). While such inefficiency is understandible in a natural system, an intelligent designer, if one existed, would be expected to have more efficient system of variation and development.
That's why the naturalistic explanation is considered the one that is simplest and best - it matches the observation on a natural and inefficient system. Variation happens because the universe does have an element of randomness. However, selection ensures that only those variants that can survive and reproduce do survive and do reproduce.
I hope that's clear. It's the result of trying to summarize and simplify several books' worth of information.
The "reverse evolution" slant comes directly from Capecchi:
"We've shown some of the elements involved in the process of evolution by reversing this process and reconstructing a gene that later became two genes"
That should read: "it matches the observation of a natural and inefficient system."
But in a way, that typo demonstrates my point. That neural misfire is an example of a minor variation that can occur in a natural system (my brain and fingers).
Heh.
No, my concern is understood. Thanks.
Thanks to all of you for taking the time to set me straight. I appreciate the patience of each of you in responding to my questions, even if they seem a bit basic. I was really hesitant to post here because I have seen some of the blistering attacks on people who don't understand science, but I appreciate the respect you've shown me.
My comment was based upon what I have seen in some of the ID writings/debate about the origins of the universe. There is an argument attributed to cosmologists by IDers that ""God caused it" is not a scientific answer to how the universe began because, inter alia, the origin of the universe is outside the scope of scientific inquiry." That statement itself may certainly be IDers bastardization of what some cosmologists and astrophysicists have said, but the argument is out there, and that was what motivated my question.
I stand corrected (and more informed).
What you need to understand is that evolution doesn't happen for reasons, but as a consequence of historical contingencies. The Hox1 gene was replaced by two genes because the one gene was duplicated -- a random occurrence, not part of some plan. The two independent genes were then subject to independent mutations. Apparently this resulted in a slight survival advantage over the single gene -- according to the researchers, the two genes work slightly better than the single combined gene. OTOH, there were two gene duplications, resulting in four different genes, but the other two have since disappeared -- presumably because they were never subjected to mutations that led to an advantage (or enough of an advantage; or the advantage later became disadvantageous; or ... the story can be arbitrarily complex).
That's a bit confusing. I thought you were asking about biological causes; now you seem to be referring to cosmological causes.
I'm not well read in cosmology, but I would tentatively suggest that "outside the scope of scientific inquiry" just refers to the infinite regress of causes. Or to put in another way: We currently understand certain things about our universe (structure, size, dimensions, age, cosmological expansion, physical constants, etc). We don't know exactly why those things are the way they are. If we ever find out more, there will still be the question of exactly how those things came about. There's always going to be something outside of what we know, and what we can find out.
If we can't know anything about something, and can't find out in any way at all, that means that there will always be something outside of the scope of science.
Or something like that.
How did this PYGMIES+DWARVES thing start?
The "debate" stuff I have read from the IDers points out what they see as the failings in many areas of science, from cosmology to evolutionary biology, astronomy, etc. My point was that one-counterargument IDers attribute to scientists regarding the IDer argument that "God created the universe" is that the argument is not scientific because the "cause" is outside the scope of science. I was (probably improperly) transplanting that argument regarding cosmology to biology.
The blistering attacks come against people who are arrogant, insisting that they know the truth when they are in fact ignorant, people who are intellectually dishonest, refusing to credit information and explanations simply because they don't like them, people who are plain dishonest, misquoting people and misrepresenting facts, and so on. You displayed none of those characteristics; you get the respect you give.
There is an argument attributed to cosmologists by IDers that ""God caused it" is not a scientific answer to how the universe began because, inter alia, the origin of the universe is outside the scope of scientific inquiry.
"God caused it" is not a scientific answer to how the universe began, not because the origin of the universe is outside the scope of scientific inquiry, but because "God caused it" is not and cannot be the result of scientific inquiry. If in fact there is such a thing as God (whatever that means) and God in fact caused the universe to come into being (whatever that means), no amount of empirical evidence could establish that as a fact, distinct from there being no God or God not causing the universe to come into being. No matter what we learn about the universe, those two views would remain unsubstantiated metaphysical speculations.
Also, "ID" is the empirical thesis that there are biological systems too complex to have evolved and therefore they must have been designed. Talk of cosmology and origins is goalpost shifting; theistic evolutionary biologists believe that God created the universe but reject the ID thesis (as they should, because it is thoroughly fallacious). Despite what dishonest goons like David Heddle say, ID is not the general metaphysical notion that the universe has an intelligent cause or operates upon intelligent principles; if that were the case, then Einstein was an IDist.
A classic post:
http://pharyngula.org/index/weblog/comments/if_you_doubt_this_is_possib…
I was (probably improperly) transplanting that argument regarding cosmology to biology.
That's baffling, because your previous comments don't seem to resemble that argument at all. You asserted "there appears to be no answer, in science, for what causes the mutations in the first place" -- that's not an argument made by IDers, that's a something you are asserting. I have no idea why you would make such an assertion, since virtually any source that discusses mutations refers to numerous known causes for them; scientists certainly don't say that the cause of mutations is beyond the scope of scientific inquiry. Your wrote Christians can say "God caused them" -- sure, and they can say that God causes rainbows and the Earth to go around the sun, but that doesn't imply that rainbows or the Earth going around the sun are beyond the scope of scientific inquiry.
Truth Machine:
I have seen a ton of information (including one reported court case) where ID was shown to be nothing more than "dressed up" creationism (new name for an old creationist argument). If so, I agree that ID does not belong in our science classrooms because it would violate the separation of church and state.
I also believe that God created the heavens and the earth. My religious view, however, doesn't really help me live in this world at this time and place and explain physical phenomena in a satisfactorily robust manner. Saying "God will prevent me from falling off the planet" may be true to me because of my belief in God, but it really doesn't explain (in any non-frivolous way) the concept of gravity. I can't believe that there are Christians who don't see this simple proposition.
I also believe that natural selection is a valid provable method by which certain traits are selected for and certain traits are selected against. Again, I don't understand the details of all of the biological mechanisms, but it seems very clear to me that it is a valid theory.
If in fact ID is trying to claim it is a science, then it should meet the criteria for scientific inquiry. However, valid criticisms or questions regarding science should not be dismissed as ID ridiculousness. That is merely shifting the burden of proof. For example, the earlier post stated that mutation just occurs as a result of historical contingencies and not because of causation. However, I was under the impression that action and/or effect presumes causation. If science has no better answer than "it just happens" then on what basis (besides "it's not science") can anyone really level a valid criticism on the person who claims "God caused it"? In other words, isn't "It just happened because of historical contingencies" no more provable via the scientific method than "God caused it"?
I think I see the confusion here, DP. You talked about not knowing the cause of mutations, and then you talked of "God causes the universe" being beyond the scope of scientific inquiry. Yes, "God causes the universe" and "God causes mutations" are beyond the scope of scientific inquiry, but that doesn't mean that we don't know what causes mutations, because "radiation causes mutations" and "free radicals cause mutations" are not beyond the scope of scientific inquiry. You seem to be treating radiation and God as being on a par as possible causes, but they aren't; one is a physical phenomenon that can be measured and studied, and the other is a metaphysical concept.
I get it.
Thanks.
valid criticisms or questions regarding science should not be dismissed as ID ridiculousness
valid criticisms or questions are not dismissed -- scientists raise and respond to such criticisms all the time.
For example, the earlier post stated that mutation just occurs as a result of historical contingencies and not because of causation.
No, it states no such thing. Historical contingencies are such things as meteors striking the Earth at such and such a time at such and such a place or a cosmic ray striking a DNA molecule at such and such a time at such and such a place. What in the world would cause you to characterize that as noncausal???
"It just happened because of historical contingencies" no more provable via the scientific method than "God caused it"?
Uh, no, because science can prove that this or that historical contingency occurred. "It just happened because of historical contengencies" was simply a characterization of the operation of evolution as contrasted to teleological/planned/purposeful notions of evolution setting out to do something or other, which was implied by your question about efficiency. It was not intended as a complete or final claim as to how something happened. Frankly, I find your misunderstanding here nearly as hard to believe as your finding it hard to believe that Christians "don't see this simple proposition", but our difficulty in grasping how others can fail to understand things that we find straightforward doesn't change the fact that they do have these failings.
As I look back over the comments, I believe I really did just misunderstand the nature of what I called the "it just happened" argument. Your last post really set it out for me. I appreciate it.
Trying for more clarity:
In other words, isn't "It just happened because of historical contingencies" no more provable via the scientific method than "God caused it"?
Science can't prove that "God caused it", and it can't prove that "God didn't cause it"; neither of those is within the scope of science. The claim that Hox1 split into Hox1a and Hox1b as a matter of historical contingency was not presented as versus "God did it", but rather as versus "for the purpose of producing two different functions" -- within the scope of our scientific understanding of evolution. It was intended only to explain, on a scientific basis and within a scientific framework, why something apparently inefficient occurred. It was not a metaphysical claim that God is not directing evolution, it was a statement about evolution as science models it, based on scientific observation of how it functions. If one does subscribe to the idea that God directs evolution, then it seems it's up to such a person to explain why God does something inefficient, but it's not a problem for science, because the inefficiency is quite explainable within the scientific framework.
I get it.
Thanks.
I appreciate it.
Cool; You're welcome. And I appreciate your desire and willingness to engage in an honest exchange of ideas.
Quite right. I agree with you. I think that what happens (and I seem to have fallen into the trap myself) is that many non-scientists try to overstate the actual claims of scientists in order to set up a straw man to knock down. I should not have done that.
DT:
I think you have already reached an understanding, but I just thought I'd point out that it now looks to me that you are trying to clarify the difference between, and the limits of, methodological naturalism versus metaphysical naturalism.
I didn't quite understand the thrust of your questions ("cause" is perhaps an unfortunately ambiguous word, depending on your philosophical assumptions). But I did try to emphasize that I was speaking in a methodological naturalistic frame.
I think that what happens (and I seem to have fallen into the trap myself) is that many non-scientists try to overstate the actual claims of scientists in order to set up a straw man to knock down.
Well, looking back, I can understand how the misunderstanding happened, because within your framework my opposition of "historical contingency" to "for reasons" seemed to be about God's reasons, but I wasn't responding within that framework and didn't realize at the time that you were thinking within that framework -- I glossed over your comments about being a Christian and took your question to be a straightforward question about the working of evolution.
I had a similar experience yesterday, when a friend and I went to a restaurant with his wife following in the car behind us. He pointed to the restaurant as we continued on to find parking. After we pulled in, she was nowhere in sight, and we fretted about her getting lost, specualating that it might not have actually been her behind us. We walked to the restaurant and stood outside for a while, hoping that she would drive by. We found a phone and called her cell phone but she didn't answer. My friend walked back to where we parked to see if she was there waiting for us, but she wasn't, and he walked back. We were a bit lost as to what to do next, when she came walking down the street from the other direction, smiling. It turns out that she had seen him point to the restaurant, knew exactly where it was, drove around the block to a different parking lot, stopped into a store to look at decorations for their Hawaii condo, and assumed we would have gone inside the restaurant and relaxed at the table. At that point it all made sense, given the well-established fact that she has a poor sense of the passage of time. But it's as though we were living in different universes, operating under very different sets of assumptions.
Prof. Myers,
Super post, interesting paper.
They're only swapping around the protein coding region? Does this mean they've got an b1 introns in between the a1 exons?
Also: you have a minor error in the 7th paragraph:
"The difference in sequence suggests that Hoxa1 and Hoxa2 could have different functional roles,"
You probably mean Hoxb1 instead of Hoxa2 there.
I've still some problem understanding why the two genes where better than the single one, if the mice look normal.
Anyway I suppose that using a single gene could be equivalent in the mouse, but in the animal where the duplication happened could have been better to have the
duplication, then getting a more complex system the functionality that made the difference are no longer important.
Or maybe the one with duplicated genes where just more horny and reproducing faster :)
Sorry.. I'm just a computer scientist trying to figure out what he's missing....
That's the thing: two genes are not necessarily better than one. What it is saying is that we have a process operating in evolution that tends to pile up complexity by error, and that the kind of subfunctionalization we see in Hoxa1 and Hoxb1 happens spontaneously. Your problem is that you are unconsciously trying to impose directedness and purpose on a system that is directionless and purposeless.
Chris Mitchell: The way I put it is that very often selection can be best looked at as applying to the least. So lots of weird and sometimes rather crappy stuff survives because it wasn't the worst.
(re: mechanisms of mutations) You would think that people who had survived the popularity of the Teenage Mutant Ninja Turtles would have at least heard the word mutagen, even if TMNT totally botches everything else scientifically speaking.
sorry for the wrong question..
Let's say, why Selection has made win the duplicated genes version?
(It could be that I really miss a big point, sorry)
Btw, I don't believe in ID, I'm just trying to understand if it's possible to know
why the ones with duplicated genes have been more lucky...
(sorry for the too strict technical jargon that I'm using)
Yes, you are missing a very big point: evolution is not synonymous with selection. Selection is the process that makes sure everything works, more or less, but the bulk of evolutionary changes are not the product of selection -- they are changes that are good enough, not best, that don't destroy the organism.
DP:
There exists slightly different answers to your question too. But it will be a little messy.
"There is an argument attributed to cosmologists by IDers that ""God caused it" is not a scientific answer to how the universe began because, inter alia, the origin of the universe is outside the scope of scientific inquiry.""
Causation is a broad question. Much of the discussion concerns "common-sense" "folk physics" in philosophy (effective causes, final causes, et cetera) and theology (first causes). As usual common sense doesn't cut it in science, so the description becomes different here.
First there is a description of how causation proceeds generally, causality. This describes how cause-effect behaves. Originally, cause-effect was thought to be ordered by time alone. It was the success of Einstein to describe causality to be ordered by space and time. It came together as spacetime in his theory special relativity. For instance, we now know that no signal proceeds faster than light. There are a lot of results when generalising this desription. For instance, time machines becomes forbidden.
Second there is desription of what causation means specifically, system evolution. This describes which causes and effects we see. Most systems seem to proceed deterministically, at least when we have the full description of it. Quantum mechanics throws several wrenches into the works. For instance, we now know that its randomness is genuine, ie it is there even when we have the full description.
Genuine randomness means that some things "just happen". But the system that it happens in is still evolving causally - it is the system that permits randomness or not, and determines the probability distribution. Causality is still king - but it has a court jester.
Regarding origins (first causes) one can first note that neither evolution theory nor cosmology theory need it to work selfconsistently. Evolution as a theory works on the life we observe. The start of life, abiogenesis, is a completely separated phenomena and has its own theory. The same happens in cosmology. Cosmology as a theory works on the universe we observe. The start of the universe is a completely separated phenomena.
But there are ideas of the start of the universe. Since natural theories can't use a nondefined first cause, neither supernatural nor natural, it is simply avoided.
There seems to be at least three different working methods to avoid it that at one time or other has been seriously discussed.
One is to use the genuine randomness of quantum theory and assume the universe tunneled into being. The final theory must describe the intial system but the desription is enough.
One is to use the property of boundaries and assume there are none to the universe. In this case there is no first time/first cause due to the topology of spacetime - it is to ask "what is south to the south pole".
One is to use the eternal cosmologies. Each universe is assumed to be embedded in a larger multiverse setting from which they spawn randomly. In this case the system has always existed.
TL:
Thanks for the insight.
Another way to summarize the distinctions: Evolution depends on three factors, none of which are sufficient by themselves:
1) reproduction "in kind" provides a path for all life, leading... somewhere. That is, the basic goal of life is to survive, not as individual organisms, but as lineages continuing into the future. How they go about that is not specified (yet).
2) mutation introduces differences among the individuals comprising each lineage. This introduces forks in the path, different ways to go about surviving and reproducing.
3) selection makes the differences important to lineage survival. The individuals who best survive and reproduce, in whatever conditions happen to surround them, will de facto be better represented in the future of their lineage. Even if there are no obvious hazards around, Malthusian constraints will provide "limiting factors", which then incite competition, which becomes a hazard.
Metaphorically, differing lineages can explore various paths, committing part or all of their population to a given strategy. Some paths lead quickly to dead-ends. Others run for a while, but then run into obstacles, perhaps thrown up by the crossing of other paths. Some are blocked by the traffic already on them (Malthusian constraints). The "best" paths just keep winding on across the landscape of life....
4) adaptation is strictly derivative from the above! There is nobody insisting that any given solution for a problem is "right". The only standard is that a problem that endangers "survival" needs to be dealt with somehow, or whoever does solve it will eat your lunch and steal your mate. ;-)
DP, a peripheral comment, regarding your earlier question about mutations: You might not be aware (and my apologies if you are) that the definition of "mutation" that some of the ID/Creationists you read were using may not be the accepted scientific definition. A common tactic in arguments is to redefine terms to suit one's purpose, and creationists use it regularly.
In this case, they are often referring to beneficial mutations, or to a complex suite of genes encoding an entire system (eyes or flagella or hearts). So sometimes, the comment that mutations are "impossible" is really meant to say "all mutations are harmful" or "you can't spontaneously mutate an eye." It's based on ignorance, incredulity, and flawed probability calculations of events biologists do not claim occurred in the first place. This is discussed at length here (in particular the CB100-300 series):
http://www.talkorigins.org/indexcc/list.html#CB100
This also highlights one of the problems with creationist thinking, namely a fixation on whole, discrete systems rather than the components which make up those systems. The eye or flagellum or heart, then, is seen as an "all or nothing" scenario. I think this relates to a too-common religious tendency to think in terms of clearly defined blacks-and-whites, rights-and-wrongs, absolutes.
Isn't the flagellum one of the examples Behe cited for irreducible complexity? And the counterargument is that he is not looking at the right level? I mean, he is focused on whole organisms rather than looking at the genetic or cellular level?
Pretty much. My hunch is that Behe and such (assuming honesty on their part) are blinded by the neato-keen nature of biological systems, in a "can't see the trees for the forest" sense. As you say, Behe claims irreducible complexity in the flagellum. But it is well known that significant components of the flagellum exist independently and for different functions, showing that these components are indeed useful when not part of a "cellular outboard motor." A good discussion of the flagellum's evolution is here:
http://www.talkorigins.org/indexcc/CB/CB200_1.html
Behe took a thrashing over this in the Dover case, and I highly recommend reading those transcripts in general. There were also some good posts on this somewhere here at Pharyngula, but I'm not finding them quickly with the search engine.
It's also worthwhile to note that because we're talking about cellular organelles and soft tissues, we can't turn to the fossil record to study their evolution. That's one reason IDists spend more time on these topics.
One (of many) problems with Behe and the flagellum is that he focuses only on what a super-cool and supremely "functional" and well-designed "machine" the little rotor-whiptail propellor assemblage is in its current incarnation. But remember we're talking single-celled beasties (or cellular descendants of single-celled beasties--there's several different kinds of flagella out there, and IIRC they are also found in multi-cellular lineages, which of course themselves ultimately descend from single-celled lines).
But confining ourselves to one-celled critters, there is good reason to believe that they have been around in some form for upwards of 3-4 BILLION years (much longer than multi-celled beings, who apparently originated ~1 BYA). Some have generation cycles of minutes to days.
A quick, and highly approximate (since the length of days and years has varied over all that time), multiplication of 3.5 billion years times, oh, 350 days gives, yow, something like 1.25 trillion generations leading up to any ONE currently-living single-celled organism.
That's, very conservatively, an enormous number of opportunities for replication errors, other kinds of mutations and whatnot--good, bad, or indifferent--in just one currently-living single critter's line of descent. And how many quadrillion--or whatever other number--of single-celled critters are alive at any one time, in however kazillion many minutely and majorly differing environments, micro-environments, niches, and micro-niches? So the opportunities for variation and selection are stupendous.
In focusing only on the "propellor" system as a whole and claiming it would be non-functional if any of its "parts" were missing or less than fully "functional," Behe gives himself permission to ignore all the stupendous number of previous versions of ancestral cobbled-together assemblages or semi-assemblages of more or less similar "parts," the differing environments in which THEY might have been funtioning, etc.
I'm agreeing that he focuses only on one level to the exclusion of others, but he not only excludes the "higher" levels of whole organisms, interactions of those organisms with each other and different organisms, and their environments (and all other environmental micro-niches spread over all the planet's surface to some considerable depth and height over most all of the planet's history), but he also excludes all the potential lineages of assemblages, sub-assemblages, parts, sub-parts, and all the imaginable differing possible "functions" of all of those "lower" levels--all just on his say-so: his unsupported assertion that no possible dissolution, decomposition, dis-assemblage, or reduction of his little "propellor" thingy exists.
The guy is like a driver with tunnel vision who has been in a car accident with an intersecting automobile trying to explain away the wreckage strewn all over the highway to the investigating officer on the basis that no other automobile could have conceivably existed in the first place just because HE, wearing his blinders, wasn't able to see them.
Reduction has been such an enormously successful strategy for science that--even without claiming that it's the only or best strategy--any thinking person should be immediately suspicious of Behe's claim.
And that suspicion is perfectly justifiable even WITHOUT knowing how little success his similar past claims (blood-clotting cascade, etc.) have enjoyed, what progress has ALREADY been made in "reducing" the flagellum (toxin-injection functions, etc.), or how wilfully Behe has to work to maintain his own state of ignorance and isolation from the accumulating knowledge about his "irreducible" systems (the stack of dozens of articles and books in the Dover trial that he had never read, etc.)
(The following is an informed layman's understanding of the issues. The professionals here may want to correct any of my misunderstandings.)
Two comments. First, while scientists can clearly identify many processes that cause mutation, it may not always be possible to say exactly *which* mutagen caused a given mutation. For the Hox gene duplication, one or more mutagenic candidates might be identifiable, but it is unlikely that we will ever know for certain precisely which mutagen caused that particular gene to be duplicated at that particular time in which particular organism. All Evolution says is that we can identify possible or even likely causes.
The second is in regard to the comment about, "the two genes work slightly better than the single combined gene". The question was why that should be the case. The question revolves around what "better" means. When people normally think of "better", they imagine a given task, and compare the function of two different tools. The tool that is "better" at the task is the "better" or more valuable of the two tools.
In evolution, the problem is that the task changes as well as the tool. In this case, "better" means "better at what the genes do today", or "more fit in today's evo-devo environment". Almost by definition today's genes work "better" in today's organism than yesterday's genes do, because they have been selected for (and in) precisely that environment. That doesn't mean that today's genes *are* "better" (in an absolute sense) than yesterday's gene at some other (albeit closely related) task in some other environment. It might be that yesterday's gene worked "better" in yesterday's mouse than today's genes would have worked in yesterday's mouse. All we can say is that in today's mouse, today's genes work better than yesterday's gene does in today's mouse.
When you start to use the more common notion of "better", you start wading into a question of "value", or the question of, "what are the genes *supposed* to do"? That gets into the question of "purpose" or "intent". Those questions aren't meaningful in a scientific sense. IDist's and creationists constantly confuse the evolutionary notion of "fitness" with the metaphysical notions of "purpose" and "intent".
David:
That was a nice picture!
DP, Stevepinhead:
"IIRC they are also found in multi-cellular lineages"
They are and then they are called cilia.
"Cilia are structurally identical to eukaryotic flagella, and the two terms are often used interchangeably. In general, though, the term cilia is used when they are numerous, short and coordinated while flagella is used when they are relatively sparse and long. The name cilium may also be used to emphasize their differences from bacterial flagella."
"Cilia are found in all animals, although nematodes and arthropods only have non-motile cilia on some sensory nerve cells. Cilia are rare in plants, occurring most notably in cycads." ( http://en.wikipedia.org/wiki/Cilium )
"On the surface of nearly every cell in the body is a slender protuberance called the primary cilium." In humans they are most important in the nose, eye, ear, lungs, gastrointestinals, and kidneys.
( http://www.hhmi.org/bulletin/sept2005/pdf/Cilia.pdf )
They are also important in the sexual organs (transporting all sorts of things :-) and during embryo development. PZ has a nifty post on how cilia and their direction of spin sets up the right-left asymmetry of some organs in the body. Ie how the body knows right from left. ( http://pharyngula.org/index/weblog/comments/generating_right_left_asymm… )
Very good point, Scott. I as a layman have always had a hard time separating the concept of "fitness" with the metaphysical concept of "purpose."
Based on what you said, though, can't someone believe in evolution (mutations and/or changes happen, for whatever reason), natural selection (characteristics that are more helpful to survival actually do survive down through successive generations more so than characteristics that are not), AND God? If the idea is that science doesn't concern itself with the purpose behind the mutations, it would seem to be a metaphysical, rather than scientific, inquiry, then, as to what that "purpose" or "intent" of the mutation was. The fact that certain characteristics are then selected for or selected against, to me, doesn't implicate any religious ideas at all. It is strictly a logical deduction which has been borne out by the evidence.
Or, does science REQUIRE that the mutations and/or the selection be intentionless and purposeless? If so, why?
Just 2 points, one quick and one not so quick:
Firstly, there is an incorrect statement in the otherwise clear and well-written description of the paper: there is no evidence of Hoxc1 genes in MAMMALS. The conflation of data from mammalia with vertebrates in general tends to bug those of us who work on by far the largest group of vertebrates (fish). It turns out both zebrafish and medaka fish DO in fact have a Hoxc1 gene, though we don't know what it's function is (see reference 1 below). Interestingly, the Coelocanth fish, sometimes called a "living fossil", also has a Hoxc1 gene (ref 2), suggesting that this gene was lost in the lineage leading to mammals and retained in the lineage leading to fish.
Second point: it's extraordinarily hard to elucidate the total functions of any gene, but particularly one that plays a key role in early development. One of the central dogmas of "evo-devo" is that genes get re-deployed to multiple functions through evolution. A transcription factor like a Hox gene may be recruited to other functions, and gene duplication can provide the spark to make that happen. As we have found in zebrafish, they find that the coding sequences of the two genes aren't fully interchangable (ref 3). But what does this mean exactly?
Basically I'm suggesting that it is very tenuous to say that their evolutionarily reconstructed mouse is completely normal. Perhaps its surprising that it looks as normal as it does, and I do believe the evidence they provide to support this. On the other hand, they only describe the earliest phase of expression of the Hoxa1 gene. In Xenopus frogs, chickens, and mice, Hoxa1 has a later phase of expression in clusters of cells in the midbrain (ref 4). This same laboratory described a much later expression pattern for the Hoxb8 gene too (ref 5). Sorry if this is overly technical, here's the take home message:
These genes are really complex, and do different things at different stages of the life of the animal. Thus while it is cool that they can get a decent looking mouse with one gene in place of two, they definitely have not proven that it's 100% healthy. If it was released into the wild, would it be as successful as a normal mouse? This may seem like splitting hairs, but it really isn't. If a mouse with two copies of a Hox1 gene is SLIGHTLY more fit than a mouse with one copy, natural selection can give you a population of mice with two genes instead of one. So although I think it's a really cool and provocative paper, I would say it's very premature to conclude that the duplication that gave rise to Hoxa1 and Hoxb1 didn't add any functions or complexity to the organism.
That's it, thanks!
References:
1) Development. 2001 Jul;128(13):2471-84.
2) Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1084-8.
3) Development. 2002 May;129(10):2339-54.
4) Dev Genes Evol. 2003 Aug;213(8):399-406.
5) Neuron. 2002 Jan 3;33(1):23-34.
While the relaxedly-religious to agnostic to non- or anti-religious majority here probably see no evidence indicative of some "higher" metaphysical purpose--beyond such things as the "purpose" (in the sense of tendency) of replicants to, um, replicate, and the possibility that opens up (through "ratcheting") that at least some lineages of replicants may persist long enough and grow complex enough to start contemplating concepts like "purpose"--and many of them therefore strongly DOUBT that there is any such purpose, that doesn't necessarily mean that there couldn't BE some purpose above, beyond, beneath, or behind it all.
That is to say, as has been said here many times and many ways, science doesn't really speak to those metaphysical questions.
So, no, science doesn't REQUIRE that life or evolution lack (metaphysical) purpose or intent. Science is a pragmatic approach to reality, ratherthan a philosophical or religious approach to meta-reality.
Oh-almost a big OOPS!--Torbjorn, thanks for the flagella-cilia info!
RE DP
As I understand it, a common thread in much of Christian theology is that God is both the transcendental originating cause and the immanent sustaining cause of all of existence. In both cases, what such theology is dealing with are ultimate causes. However, empirical science does not deal in ultimate causes, whether the subject of study is evolutionary biology, physics, chemistry or cosmology. Given this, one could easily argue that religion and empirical science are speaking entirely perpendicular to one-another.
Then again, there are those who would argue that as empirical science deals entirely in naturalistic explanations, the best worldview is the simplest, and in thus argue for a fully naturalistic worldview. However, in my view, while the latter approach may be a valid one, at this point one is no longer dealing with empirical science, but in philosophy.
DP:
As Stevie says, no, science doesn't require evolution to be purposeless. Neither does it require that any "purpose" be undetectable. But under evolutionary theory there is no reason to expect a guiding divine hand, and the evidence thus far hasn't shown anything of the sort.
Some here, PZ included (please correct me if I'm mistaken!) would advise you to reject the notion of a guiding divine hand if none is detectable. The question is, if it exists but is undetectable, then how is it different from not existing at all? You end up contemplating your definition of reality and how you determine it.
You say "under evolutionary theory there is no reason to expect a guiding divine hand." I would agree that there is no reason to expect a guiding hand in natural selection (I think there is still room to argue a "guiding hand" could have had a say in what mutations occurred, when, why, and how). As I stated before, natural selection is just a matter of deduction to me (to take a frivolous example, since we all need hearts to function, there should not be many humans walking around without hearts because they don't survive).
However, you are now imposing scientific arguments, constraints, and burdens of proof on something you claim is not scientific in the first place. If science truly doesn't deal with ultimate causes, why should PZ or anyone else (especially a scientist who supposedly does not deal with ultimate causes) "advise" me to reject the notion of a divine guiding hand regarding ultimate causes because you cannot "detect" it in some scientific manner? Why should I be tied to science and its evidence and its structures and its proofs when we are discussing something that all agree is not scientific?
rrt:
I may have conflated your comment with Timothy's. If what you were referring to was not ultimate causes, then I misunderstood. My mistake.
My point still stands, however, with regard to ultimate causes. It seems very unfair to require someone contemplating ultimate causes to abide by scientific structures, proofs, etc.
rrt:
I may have conflated your comment with Timothy's. If what you were referring to was not ultimate causes, then I misunderstood. My mistake.
My point still stands, however, with regard to ultimate causes. It seems very unfair to require someone contemplating ultimate causes to abide by scientific structures, proofs, etc.
I don't mean to imply that science says you should be tied to it and it's evidence, structures, and proofs. I meant they would advise you philosophically...sorry if I gave confusion there. Indeed, though I'm not qualified in philosophy, I agree with Timothy Chase's statement.
Regarding the guiding hand, however, I still ask why you think there is room for it. Scientifically, if there is a force having a say in what mutations occur when, why and how, then its effects should be detectable. If its effects are indistinguishable from "no force," then scientifically we must go with "no force" until better, contrary evidence appears. Non-scientifically, sure it could exist, but then we're back to contemplating how we define reality, and why we would make an exception in this case, and if exceptions to that rule should be made at all.
Ah, yup, but it was still a good question to ask! :) And again, with all this I don't want to seem like I'm saying you can't believe whatever you wish, but I am trying to convey some of the questions I myself contemplate regarding theistic evolution.
Oh, and I forgot to point out something in an earlier comment. You'd stated that evolution was equivalent to mutation, but it's not. Rather, it's the changes that happen over time as a result of natural selection and other forces (I suppose that's overly simplistic...) Mutation is what supplies raw material to keep the process going, and is essential to evolution as we know it on Earth, but not technically essential to evolution itself.
I appreciate all of your thoughtful comments. That's why I think this is one of the best science blogs!
Good point about the fish Hoxc1; that's fixed.
It's also true that it is only an apparently normal mouse, and there could be subtle differences that we just can't detect. The authors were careful in their figures to label it "~normal".
Ah, that explains it. My normal day was beginning to seem more and more ~normal.
Sounds like they should run some of those mice through a broad suite of mazes and other cognitive tests. (With "wild-type" ancestors as controls, of course.)
And yeah, this was a great article! Nicely structured for dabblers to skim the overall points, while the hardcore types can meditate upon the diagrams and acronyms. ;-)