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Signature in the Pseudogenes, Part 1

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May 10, 2010 Tags: Genetics

Today's entry was written by Dennis Venema and Darrel Falk. Please note the views expressed here are those of the author, not necessarily of The BioLogos Foundation. You can read more about what we believe here.

Signature in the Pseudogenes, Part 1

In our previous post, we likened comparing genomes of related organisms to reading alternative history novels. We noted that before two species diverge, they share the same “backstory” but then go on to accumulate changes after separation.

One interesting feature of looking at genomes is that often we can find the mutated remains of once-functional genes. These are called pseudogenes, or “false genes.” Pseudogenes might be part of a shared backstory for two species, or they might crop up independently after two species go their separate ways. Either way, they are easy to spot at the molecular level because they retain a lot of similarity. For example, here are the DNA sequences for the start of one particular gene1 in several species (for our purposes, its function is not important).

As you examine the sequence of letters above, note that DNA contains a four letter code. This string of “letters” is made up of the molecules adenine, guanine, cytosine, and thymine strung together within the large super-molecule, DNA. Our cells read the encoded instructions and, interpreting the code, build each of the different proteins required for the maintenance of life.

Note that the instructions have changed a little since these five species had a common “backstory” (ancestor). Despite the changes, for the dog, mouse and chicken, the protein is fully functional. This is not so, however, for the chimp and human. The “dot” (highlighted by the red arrow) means that one single letter of the instructions has been deleted. This change would be like finding this sentence in the first edition of a book:

THE BIG RAT HIT THE RED MAT.

But, in the second edition of the same book, we find this instead:

THE BIG RAT HTT HER EDM AT

The sentence has no meaning anymore, but, as we compared the first and second versions of the book, we would be able to tell exactly what had happened: the letter “I” had been deleted from the sentence, and everything following would be messed up. A single deletion throws off the whole code from that point on. Thus, for chimps and humans, the instructions become gibberish, and the protein molecules produced according to that gene’s instructions are now badly mangled and unable to function.

As you go back and examine sequence in the human/chimp pseudogene, notice how both species carry the exact same deletion. This suggests that the occurrence of this single deletion occurred in one individual, a common ancestor with whom both species have a shared backstory.

Let’s return to our book analogy. Presumably all copies of the second edition had the exact same non-functional sentence about the BIG RAT. If someone was to examine two second edition copies of the book, each of which were missing that same letter, “I,” it would be unthinkable to propose that the exact same mistake occurred independently in the printing of each of the two books. Similarly, it would be incorrect to propose that the new incoherent sentence had some important meaning which literary scholars will discover some day. We would know, plain and simple, that a mistake had occurred. Anything other than that would be highly contrived.

Today both chimps and humans carry the exact same mutation because they both have the same backstory. However, it is even more poignant than that. There are 20,000 pseudogenes in the human genome. Each has its own unique backstory. Each can be traced out in the same manner we have just done for this one.

The hypothesis of common ancestry makes precise predictions about how pseudogenes will be distributed in related species. Once a gene has been mutated into a pseudogene in a certain species, that pseudogene with its specific inactivating mutation will be passed on to all descendents of that species.

The figure below demonstrates this for a specific pseudogene, which we will term pseudogene “y.” Note that in a very specific individual at a very specific time, gene “y” underwent a change in its code—it mutated. That altered code was passed on to the subsequent generations and ended up in two daughter species, Species A and Species B.

Now consider a second gene, which we call “x.” It also underwent a mutation, but did so earlier in the lineage. Let’s call the new mutated form of this gene pseudogene “x.” This is shown in the next figure. Since this mutation occurred earlier in the lineage in an organism that was a common ancestor to Species A, B, and C, all three of these species carry the abnormal, non-functional version of “x.” The lineage to species D, however, had already broken away. It does not carry the mutated version of “x.”

Finally, consider another gene, which we’ll call “z.” This gene is perfectly functional in Species A, B, and D. However, when you examine its code in Species C, guess what? It carries a non-functional pseudogene. What do you think has happened here? This is a recent change, so recent that it occurred in an individual whose ancestors only went on to become Species C. Here is a summary figure which illustrates the time at which each of the three mutations occurred and the ramifications of each change.

In this example, since gene “x” is mutated to a pseudogene in the common ancestor of species A, B and C, we would expect to find this pseudogene, with the same exact inactivating mutation, in these three species. Similarly, the pseudogene version of gene “y” with exactly the same code-change should be found only in species A and B. Finally, there are many cases in which a pseudogene is found only within one species, or, at most, a couple of closely related sister species. Pseudogene “z” is our example of that.

If life really does have a backstory of this sort, then you can see the power of this technique for tracing the lineage. It allows us to trace the history of life, species by species. Interestingly though, there have long been other—non-genetic—ways of tracing life’s history. Biologists have been using these alternative methods for many decades. For example, by examining fossils (paleontology) and tracing changes in body structure (comparative anatomy), the history of life had already been pretty much worked out before DNA sequencing data ever came into the picture.

For the most part, the data which are emerging from DNA sequencing projects simply verify that which biologists have known for years through these other methods of exploring life’s history. Still, the results are extremely gratifying in their consistency. In science, one looks for corroborating evidence. If the DNA data had suggested totally different lineages, then there would have been good reason to doubt the common descent hypothesis. Such is not the case though. The supporting data keep piling up; there is no longer any doubt.

Remember how science works. If there are multiple lines of evidence—each internally consistent with the central overarching principle—a consensus is reached. The theory is judged to be correct and the scientists move on to further explore its ramifications.

If the theory of common descent is true, then it also makes predictions about what we would not expect to find at the genetic level. We go on to explore this topic in our next post.


Dennis Venema is professor of biology at Trinity Western University in Langley, British Columbia. He holds a B.Sc. (with Honors) from the University of British Columbia (1996), and received his Ph.D. from the University of British Columbia in 2003. His research is focused on the genetics of pattern formation and signaling using the common fruit fly Drosophila melanogaster as a model organism. Dennis is a gifted thinker and writer on matters of science and faith, but also an award-winning biology teacher—he won the 2008 College Biology Teaching Award from the National Association of Biology Teachers. He and his family enjoy numerous outdoor activities that the Canadian Pacific coast region has to offer. Dennis writes regularly for the BioLogos Forum about the biological evidence for evolution.
Darrel Falk is former president of The BioLogos Foundation. He transitioned into Christian higher education 25 years ago and has given numerous talks about the relationship between science and faith at many universities and seminaries. He is the author of Coming to Peace with Science.

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Harry - #13341

May 12th 2010

The statement “ID has no problem with common descent” (or similar) is continually presented by ID advocates in the face of compelling evidence for it that they know they can’t explain away to a scientifically trained audience. This is despite the obvious fact that virtually no ID advocate that anybody can name, as Unapologetic Catholic pointed out, actually accepts common descent. All of those mentioned above are simple biblical creationists, divine creation of Adam and Eve from whom all humans are descended, garden of Eden etc etc. They just want to be able to ignore (for political/theological reasons) mountains of unambiguous and clear data supporting common descent while attempting to argue elsewhere for “weaknesses” of evolutionary theory or what they seem to call “(Neo)Darwinism.” Sorry, if you can’t accept obvious and decisive data that clearly points in one direction only you don’t get to try comment on areas where the data is less clear.


Bilbo - #13348

May 12th 2010

UC: Has any DI Fellow stated that common descent is well established?  Yes—-one person.  That person then qualified his answer so as to contradict himself entirely.

I’m not sure if you mean Michael Behe, but no he has not contradicted himself entirely or at all.  And he argued for common descent in his book, The Edge of Evolution, using the same kind of evidence that Dennis and Darrel present here. 

But I agree with you that most of the leaders in the ID movement don’t accept common descent.  Michael Behe would be the exception (and Mike Gene, if we include him in the ID movement, from which I think he would prefer to distance himself).

But there is no logical contradiction between ID and common descent.


R Hampton - #13373

May 12th 2010

“t there is no logical contradiction between ID and common descent.”

I agree, so it begs the question why almost everyone at the Discovery Institute is dead-set against common descent.


Bilbo - #13381

May 12th 2010

Hi R.H.,

I suspect there are a combination of theological, scientific, and political reasons.  As to the scientific reasons, apparently the are some “puzzles” that common descent has problems explaining.  But I know zip about them.


R Hampton - #13383

May 12th 2010

“I suspect there are a combination of theological, scientific, and political reasons. “

Yep


Bilbo - #13401

May 13th 2010

I thank Thee Lord, maker of Heaven and Earth, that Thou hast not made me like those DI fellows.


Argon - #13432

May 13th 2010

MAS - #13321 writes: “ID has no problem with common descent (But may have with the above presentation of Pseudogenes as they argue that a majority of genes which do not code for protein are still vital to the organism and to dismiss them on the grounds that they are the waste product of natural selection is plain wrong.”

One might ask on what basis do some who support ID and have no ‘problem with common descent’ conclude that the majority of pseudogenes would remain vital? What underlying assumptions are they making about the modes, mechanisms or constraints of how biological design was implemented that are distinct from basic, evolutionary mechanisms? I’ve not seen anything substantive from Meyer and particularly, Hunter on how their claims about the percentage of ‘funtional’ pseudogenes directly follows from ‘design’ explanations (If anything, their claims parallel that of the ultra-selectionists and the shortcomings uncovered in that particular debate is well documented).

Note that the assumptions of Meyer and Hunter are very distinct from Mike Gene’s notions of how design is implemented.


m - #13442

May 13th 2010

Argon:

“One might ask on what basis do some who support ID and have no ‘problem with common descent’ conclude that the majority of pseudogenes would remain vital?”

I’ve not found the claim about vitality, but many who support ID seems to think that the majority of pseudogenes could be useful. Behind this expectation may be theological arguments or at least some suppositions about behaviour of designer.


Bilbo - #13761

May 15th 2010

Hi Argon,

Behe offered the following analogy in EoE:  a pool player designs a shot so that certain balls end up in certain places, while allowing the other balls to where they will.  So the designer may have made sure that certain mutations occurred, while allowing other mutations to happen or not.  So it could be that most or all pseudogenes are not useful, and ID could still be true.

This is why bringing up the question of useless DNA is not all that relevant to ID.


Unapologetic Catholic - #13834

May 15th 2010

Hi Bilbo:

“I’m not sure if you mean Michael Behe, but no he has not contradicted himself entirely or at all.  And he argued for common descent in his book, The Edge of Evolution, using the same kind of evidence that Dennis and Darrel present here.” 

inconsistently with his testimony under oath at Dover and his statemtn in Edge fo Evolutionthat malaria was intentionally designed.

“But I agree with you that most of the leaders in the ID movement don’t accept common descent.  Michael Behe would be the exception (and Mike Gene, if we include him in the ID movement, from which I think he would prefer to distance himself).”

I don’t include Mike Gene. He is sui generis.  I understand Mike Gene to be the most cogent ambassador for the front-end loading hypothesis.  I am not sure how the results of front end loading are different from what is exaplainable by evolutionary theory today, but I believe that none of the Discovery Institute ID proponents could agree with Mike Gene’s analysis.


Bilbo - #13875

May 16th 2010

Hi UC,

I’m not sure what Behe said at Dover that was inconsistent with common descent.  And yes, he thinks that malaria was designed.  But for him that means that the mutations needed to get from the ancestor of malaria to malaria were designed.  So no inconsistency with common descent.

Yes, Mike Gene is sui generis.  He’s not challenging evolutionary theory.  He’s saying by front-loading a designer could have “nudged” evolution in a certain direction.  I haven’t read Simon Conway Morris’s stuff, but I hear he’s collecting a considerable amount of evidence of convergent evolution.  When we combine this evidence with the evidence of deep homology that Mike is collecting, it begins to make a very strong case that a designer could have “nudged” evolution by front-loading.


Argon - #13879

May 16th 2010

Bilbo: “This is why bringing up the question of useless DNA is not all that relevant to ID.”

Because ID reaches no consensus about how organisms arose, I agree it has nothing to say either way. The problem is not with Behe, who version of ID can accept that pseudogenes and other segments of the chromosome have no immediate function. The problem is with those who MAH referenced earlier (like Hunter) who maintain, with nothing except theological presumptions, that these sequences have important roles in the organisms *today*. Their version of ID is one in which the designer was economical and efficient. As I mentioned previously, theirs is akin to the ultra-selectionist stance where every part of the organism is important. This version of ID has one advantage but it’s not something those who promote it will necessarily exploit to evaluate their preconceptions: The hypothesis can be tested. (And it has failed - but don’t expect the failure to be published in Bio-Complexity).


Scanman - #14385

May 21st 2010

Chiming in on the ID comments above…

As a Theistic Evolutionist…it is immediately implied that we are also ID’ers.

God directed evolution…(which implies some sort of supernatural interference/influence on environmental pressures) is Intelligent Design.

I see no reason that supporters of Biologos should take any issue with Intelligent Design…only maybe with the intolerance of many ID proponents (which include those of the YEC camp).

Peace


Dave Mackey - #20573

July 5th 2010

I believe I found an article related to Jeffrey L. Vaughn’s earlier comment concerning the manipulation of glowing monkeys:
http://www.forbes.com/2001/02/02/0202transgenic.html
At least in the above article it appears that the result was simply that the monkeys did not glow - not that the monkeys died.
Additionally, I found AiG offered the following response to the pseudo-genes arguments:
http://www.answersingenesis.org/articles/aid/v3/n1/smell-of-change-pseudogenes
This article specifically highlights that at least some pseudogenes are in fact factional. An older and more extensive article (I have not read) is here:
http://www.answersingenesis.org/tj/v14/i3/pseudogenes_genomes.asp


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