Signature in the Synteny

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April 19, 2010 Tags: Genetics

Today's entry was written by Dennis Venema and Darrel Falk. You can read more about what we believe here.

In 1962, science fiction author Philip K. Dick published The Man in the High Castle, an “alternative history” novel set in a world where Roosevelt was assassinated in 1933 and where the Allies lost the second world war to the Axis. The novel gripped audiences because of the terrifyingly real “what if?” scenario where major changes in history were brought about by seemingly small events. The familiar backdrop of shared history between the novel and the real world drew readers into the narrative and made the changes that much more frightening.

In some ways, comparing the DNA sequence between related organisms is like reading alternative history novels. The hypothesis of common ancestry between similar organisms makes a very straightforward prediction about their genomes: it simply predicts that they were once the same genome, in the same ancestral species. This hypothesis also predicts that these two genomes, having gone their separate ways in the diverged species, will have accumulated changes once they separated. Like an alternative history, each genome has the same backstory, and then a history independent from the other after the point of separation.

What this implies for species related through common ancestry is that their genomes should be similar. For example, researchers have now sequenced the complete genomes of twelve sister species of Drosophila flies, including the fruit fly, Drosophila melanogaster. As you might expect, these species have similar genomes to one another. Species with the most similar genes are thought to have shared a common ancestor more recently; species with less similar genes are thought to have shared an ancestor less recently. These findings at the gene level also matched nicely with similarity of their physical characteristics.

Having the complete genome sequence of all twelve allowed researchers to compare synteny between them. “Synteny” is the scientific term for finding the same genes in the same order in two different species. (The higher the synteny, the more genes are in the same order).

Drosophila species have about 14,000 genes lined up “single file” along their chromosomes. Below is the representation of a tiny portion of a chromosome of Drosophila melanogaster. Each number corresponds to a different gene. Notice that genes, 2799, 2807, 2808, and 2828 (and others which are noted only by the ellipsis) make up a syntenic block, Similarly the genes on the right (along with others not shown) also make up a syntenic block.

Now, here are these genes in a sister species, Drosophila ananassae:

Compare the gene order of the two sister species. Can you figure out what has happened to disrupt the block of genes 2799, 2807, 2808, and 2828—genes which exist side by side in melanogaster?

Here’s a little hint:

Got it? There were two simultaneous breaks at some point in history so that 2799, 2807, 2808, and 2828 are no longer syntenic. Nor is the other block syntenic any more. Notice that in ananassae the same genes are present but they are in an inverted order. Two syntenic blocks have been broken up. We know exactly how it happened.

Now imagine analyzing this for all twelve species and—in each case—examining all 14,000 (or so) genes. The position of every chromosome break in the time since the 12 species had a common ancestor has been mapped out. 40 million years of history1 has been all laid out showing the set of disruptions of the single file order in which the genes are stored. We even know about how often those disruptions occur in a lineage: breaks, like the two described above, take place about once every 200,000 years. This rate has been fairly constant in the approximately 40 million year history of these twelve lineages. Species that diverged only recently (judged by an independent mechanism) have only a small number of breaks and a large amount of synteny, On the other hand, species which diverged longer ago (again, as judged by an independent mechanism), have a much larger number of breaks and a smaller degree of synteny.

From the theological point of view, most would have little concern with this data. We have been discussing fly species. This—in the mind of most, after all—is just divergence within the fly “kind.”

The story, however, doesn’t end there. At the same time that this was happening in flies, it was also happening in much larger organisms.

Like primates, for example.

18 million years ago, there were no humans, chimpanzees, gorillas, or gibbons on earth. Their last common ancestral species, however, was here.

Just like for flies, we can trace the changes in the single-file-order of the genes for this lineage as well. Let’s examine human chromosome #1 and compare it to the order of genes in the gibbon with whom we share that common ancestor of almost 20 million years ago.

The figure above shows human chromosome #1. The dark boxes within the chromosome are “geographical markers,” which need not concern us here. This chromosome has about 4,200 of our 21,000 (or so) genes. The gibbon has almost the same gene complement. Note, however, that there have been two inversions (the dotted lines, above) in that time. Also note that there has been some other shuffling. The genes at the left end of human chromosome #1 (about 250 or so) exist as a contiguous block in chromosome 5 in the gibbon. Similarly, if we consider the genes just a little further to the right, the next block of about 200 genes is found as a syntenic block on chromosome 9 in the gibbon…and so on. Clearly there has been some shuffling, but not a lot. Just like for Drosophila, the syntenic blocks are still largely in place.

The complete sequencing of the human and chimpanzee genomes has allowed scientists to do the same comparison with our most closely related living species. It is only about 6 million years since the common ancestor of humans and chimpanzees lived on earth. Since then, as with closely related species of Drosophila, there have been changes in synteny, but not a lot. There have been several large inversions that have been precisely mapped and many small inversions where only a few genes have been flipped. Not unexpectedly, there is even one case of shuffling between chromosomes: some genes that existed as two contiguous blocks in the common ancestor 6 million years ago, have become joined into one block in humans—the now-somewhat-famous chromosome #2.

This chromosome is made up of two blocks of genes joined together that are on totally separate chromosomes in chimpanzees and gorillas (see below). The fact that human chromosome #2 matches two ape chromosomes suggests that it resulted from a fusion between two smaller chromosomes like the ones we see as separate chromosomes in apes. This prediction was confirmed by DNA sequencing: we see all the chromosomal markers we would expect from a fusion event, and this evidence is now fairly well-known among followers of the creation/evolution discussion.

What makes shared synteny for humans and chimpanzees challenging from an anti-common descent viewpoint is that there is no good biological reason to find the same genes in the same order in unrelated organisms, and every good reason to expect very different gene orders. In fruit flies, for example, the more distantly-related species have quite different gene orders and chromosome structures, yet they all are healthy, robust species. In order words, many different gene orders can get the basic biology of being a fly done. Similarly, in mammals, many different gene arrangements can be found, sometimes even within species. In humans, many chromosome rearrangements are known that do not produce disease. Some anti-evolutionary groups claim that if human chromosome #2 was indeed the result of a fusion event, that this would have caused disease or fertility problems. This is not the case: tip-to-tip chromosome fusions do not necessarily cause defects or reduce fertility. For example, many different “races” of mice with different chromosomal arrangements are known, including examples with multiple tip-to-tip fusions like human chromosome #2. Many of these “races” of mice remain fully fertile when crossed with “normal” mice. Populations of mice with very different chromosome arrangements have also been shown to arise very rapidly in nature.

In summary, should God have wished to avoid the appearance of common ancestry between humans and chimpanzees, there seem to have been many gene orders and chromosome structures available to Him to use for either species. Indeed, we see more dissimilar orders and structures in many groups of species whose common ancestry is not controversial even for Young-Earth Creationists. Yet what we see in humans and chimpanzees are genomes that immediately give the impression of being slightly modified versions of the same genome. This pattern of genome organization similarity also fits with other independent lines of evidence (such as DNA sequence similarity and comparative anatomy) for arranging species into groups of relatedness (phylogenies) While this pattern makes perfect sense in light of common ancestry and acts as an important independent test of phylogenies, it continues to puzzle those who attempt to explain life apart from evolution.

In an upcoming post, we’ll explore how shared synteny allows researchers to predict where to find another feature of the human and chimpanzee genomes: shared pseudogenes.

Notes

1. The manner of dating the span of time over which Drosophila has been evolving is a fascinating story which the interested person can learn more about by examining the article and some of its references.

Further Reading

  • Bhutkar, A., Schaeffer, S.W., Russo, S.M., Xu, M., Smith, T.F., and Gelbart, W.M. (2008). Chromosomal rearrangement inferred from comparisons of 12 Drosophila genomes. Genetics 179; 1657-1680 Available here

  • Carbone L, Vessere GM, Hallers BFt, Zhu B, Osoegawa K, et al. (2006) A High-Resolution Map of Synteny Disruptions in Gibbon and Human Genomes. PLoS Genet 2(12): e223. Available here

  • Feuk, L., MacDonald, J.R., Tang, T., Carson, A.R., Li, M., Rao, G., Khaja, R. and Scherer, S.W. (2005). Discovery of human inversion polymorphisms by comparative analysis of human and chimpanzee DNA sequence assemblies. PLoS Genetics 1(4): e56. Available here

  • Kemkemer, Clause, Matthias Kohn, David N Cooper, Lutz Froenicke, Josef Högel, Horst Hameister and Hildegard Kehrer-Sawatzki. (2009). Gene synteny comparisons between different vertebrates provide new insights into breakage and fusion events during mammalian karyotype evolution. BMC Evolutionary Biology 2009, 9:84doi Available here


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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Edge - #10288

April 19th 2010

Interesting. I never considered evolution as an alternate history novel. I can see this being an easy way to explain this to people who don’t understand evolution or deny it. Really enjoyed the post.


Malcolm - #10289

April 19th 2010

Thanks Dennis. Those of us who have come across your online lectures will be familiar with the clarity of the modern data that you describe. It seems to me an honest Christian closely examining this has two options (as you have described in your lectures);
1). Accept common ancestry as scientifically well-established and an accurate description of history
2). Accept the appearance of common ancestry but reject it as a historical reality as a result of theological concerns - pending further scientific/theological discussions and discoveries, and consideration of the relationship between special and general revelation

Other approaches seem to be fraught with intellectual dishonesty and pseudoscientific misrepresentations.

The problem with option 2 is that as multiple lines of evidence converge (thinking recently of the fossil record), how long can “appearance” arguments be maintained?


aberg - #10296

April 19th 2010

Great information!
“Many of these “races” of mice remain fully fertile when crossed with “normal” mice.”

If these “races” of mice have different chromosomal arrangements, and they are fully fertile, what chromosomal arrangement do the progeny have?  And are the progeny fertile?

Does this suggest that hypothetically, the chromosomal differences alone between apes and humans would not prevent cross-breeding?  I always thought that a chromosomal mismatch would at best result in a sterile hybrid.

This leads to a question about the original chromosomal fusion event.  Assuming this change was a breeding showstopper, what other organism would be available for this new chromosome arrangement to breed with successfully?


Gordon J. Glover - #10299

April 19th 2010

Great post Dennis and Darrel! 

I just did some rough calcs… and with 14,000 genes, there are over 10^51968 different ways to arrange them sequentially.  That number is beyond comprehension.  For reference, there are only 10^80 fundamental particles in the entire universe.  So the designer should have had no trouble in making a clear case against common ancestry.

In fact, with so many many possibilities—the designer could have pulled this off simply by radomly selecting the gene arrangments (to maximize diversity).  Or the designer could have simply used the same order in all species (to maximize efficiency).  Either way would have rendered common descent a physical impossibility. 

So it should interest us greatly when we see this “signature” in the the cell.  Either common descent is true, or the designer went far out of his way to built the specific patterns of inherentance into the fruit fly gene arrangements.  Either way makes common descent a useful model to doing science.


Karl A - #10300

April 19th 2010

Given that one would only expect this fusion to have mutated in one individual, the fusion must not have been a showstopper for that individual’s mate, who wouldn’t have had the fused chromosomes. 

The field of genetics is certainly a burgeoning and exciting one these days.  I wonder how far these discoveries will lead us.


Karl A - #10309

April 19th 2010

Again, the challenge is laid out, for those who do not accept common descent, and who may be tempted to accuse those who do of being “liberal”, or “deists”, or worse, to jump into the mud and wrestle with this information.  I didn’t even know there were Christians who accepted common descent, yet I felt myself pushed into one of the two options Malcolm mentions above (#10289).  I wished to God I didn’t have to “go there”, but I wasn’t willing to bury my head in the sand, so I went there.  Thankfully, God (a personal, miracle-working, saving God) met me on the other side.  I’m not saying God personally validated the BioLogos positions for me, but he still loves me as I wrestle.

Don’t be afraid to think!  We all may hold 1 or 2 incorrect theological or scientific thoughts in our heads, but my Jesus says “Let he (or she) who has it all figured out throw the first stone.”


Karl A - #10310

April 19th 2010

Bad grammar. “Let him (or her) who…”
Wow, here I am, already another object lesson for grace!


Glen Davidson - #10311

April 19th 2010

Common morphology was always sufficient for scientists, and even most open-minded layperseons, to show that evolution occurred.  But the “common authorship” notion was a superficially appealing “alternative” to those who didn’t want to accept evolution.

That’s why genetic comparisons are potentially important.  Authors do not mimic synteny even when they do repeat themselves, so that even plagiarism cases are only roughly analogous to genetic similarities, not at all the same.  Indeed, nothing but common ancestry is known to produce the similarities seen in genomes—and which even anti-evolutionists accept as evidence for common descent for whatever they call “microevolution.”

Whether it’s neutral evolution, negative selection, or positive selection, the same basic copying with variation is seen, with only selection changing the frequencies.  Only evolution has any kind of explanation for this, so that even a number of IDists accept evolution—but strangely, do not fully accept the processes that actually explain the evidence.  A peculiar shift in strategy, and far from following the evidence.

Glen Davidson


Bilbo - #10313

April 19th 2010

Yes, I accept common descent.  Behe argues for common descent in his book, The Edge of Evolution, using the same kind of evidence cited here.  The question remains:  Were all the mutations random, or were some or most of them designed?  Behe argues that if significant changes required several simultaneous mutations—such as a new mechanism requiring three proteins, then they were designed.  Whether such a situation has ever been necessary is what’s up for debate.

But I object to the notion that this might have all turned out differently—as if God cannot or will not ensure that the necessary mutations would happen.  That is a theological issue that neither of the authors has the authority to decide.


Darrel Falk - #10315

April 19th 2010

Bilbo #10313

“But I object to the notion that this might have all turned out differently—as if God cannot or will not ensure that the necessary mutations would happen. “


Hi Bilbo,

I think you didn’t catch the point we were trying to make in our introductory paragraphs..  The fact is that we *do* have alternative histories!  Lots and lots of them!  That is why studying biology is the career of a lifetime.  We biologists are truly blessed

Darrel


Dennis Venema - #10321

April 19th 2010

Hi aberg,

The progeny mice are fertile, and interbreed just fine with either a fully “normal” mouse or mice from its own “chromosomal race.” During meiosis in the progeny mice, the unfused chromosomes line up with the fused chromosome and segregate normally.


Bilbo - #10325

April 19th 2010

Hi Darrel,

Perhaps I misunderstand your meaning.  Are you saying that it was only because of a lucky series of mutations that there are humans?  Or are you merely saying that there been a different series of mutations, there would be no humans?

If the second, then I have no objection.  If the first, then you’re making a metaphysical/theological determination that you are unqualified to make, since you don’t know whether the series was just “lucky” or guided.


Chris Massey - #10334

April 19th 2010

Dennis,

I’ve really appreciated your contributions to this site. I’m across the pond in Victoria. Any chance we might be able to persuade you to visit us sometime this fall to make a presentation or two at a church and maybe for the students at UVic?

We had the privilege of having Peter Enns speak at both venues last year. He can vouch for us Mind you, we did make him miss some Yankee playoff games - hopefully he’s forgiven us.


Darrel Falk - #10336

April 19th 2010

Hi Bilbo, 10325

Most definitely I am not saying the first., and if I had been your point would have been well-taken. 

Thanks,
Darrel


Dennis Venema - #10338

April 19th 2010

Hi Chris,

Thanks for your kind comments. Don’t forget that Darrel deserves 50% of the credit (or blame, as the case may be)! If you’ve read Darrel’s book you’ll know that he has a gift for making these sorts of things clear.

I’m on Sabbatical this fall, so yes, let’s talk. I lived in Victoria for three years as a teenager so it would be fun to visit again. What church are you involved with?


Chris Massey - #10340

April 19th 2010

Dennis,

Yes, kudos to Darrell as well. You guys can both come! Although I suspect Darrell might have further to travel.

It’s Emmanuel Baptist Church. They’ve been holding weekly meetings called “Faith and Reality” for a few years now. The church is located just south of the UVic campus and has been making a real effort to bring in speakers on topics that young Christians are wrestling with. When Peter came he gave a few talks at the church and on campus. I’ll ask the senior pastor, Rob, to get in touch with you.

P.S. Sabbatical sounds nice. How do I get one of those?


pds - #10350

April 19th 2010

Darrel and Dennis,

“Two syntenic blocks have been broken up. We know exactly how it happened.”

Are you saying you know exactly how the mutations happened?  That they came about by random mutation and natural selection?


Ben Vandergugten - #10355

April 19th 2010

The figure for the Drosophila melanogaster chromosome has a gene called 2808, but when the synteny is inverted in the figure of Drosophila ananassae chromosome, 2808 is replaced by 2708. Is this a typo, or did I miss something.

Otherwise, thanks for the post.


Darrel Falk - #10357

April 19th 2010

pds, (10350)

All we meant was that we know that the chromosome broke at two locations and an inversion was generated.  We know nothing about the cause of the breaks, nor do we know anything about whether natural selection played any role in the inversion becoming established and subsequently spreading throughout the population.

Ben Vandergugten (10355):

You get an A+.  That was a misprint.  Thanks for picking up on it!!

Darrel


Jim - #10363

April 19th 2010

Great article, thanks.  The alternate history combinations are mind-boggling to me (inconceivable - # #10299). Especially when adding other workable mechanisms for encoding/forwarding.  The single example we have presents alternate histories, but other isomers and functional equivalent alternatives to DNA seem staggering:  Sulfur backbones, or Si/ Si-C combinations of backbones.  Bring on enzymes for catalytic tasks.  And off to the races.  Possible.  Maybe probable non-DNA alternative histories out there.  Staggering.  Amazing.


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