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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Jim - #10365

April 19th 2010

Fascinating side-bar with pds - #10350 (“Are you saying you know exactly how the mutations happened?  That they came about by random mutation and natural selection?), standard science rejoinder (I agree), Darrel Falk - #10357 (“We know nothing about the cause of the breaks .. whether natural selection played ..”).

For fun only: I suppose some form of omniscience could predict mammal-like creatures, but stop short of predicting signatures of specific individuals.  An omniscience predicting or an omnipotence determining each random mutation (random by our definitions) for every individual and for the whole cascade of actual signature effects on offspring for 10,000’s of generations into the future. 

Arguing that omniscience/omnipotence could do it (did do it, shoulda done it), still beats me what the practical purpose of such foreknowledge/determinism would be for us. 

Inter alia, would more or less divine intervention be/have been just another alternate history – from our point of view?


Argon - #10368

April 19th 2010

“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…”

Well, that’s the death knell for ‘The Biotic Message’ hypothesis…


Karl A - #10374

April 19th 2010

Argon (#10368), could you expand?  I looked up the book on Amazon, but that was about it.


JKnott - #10393

April 20th 2010

Bilbo, Darrell, and to a lesser extent Jim—

Why do we have to choose between saying that evolution is random on the one hand and that it is within God’s providential purposes on the other?  This reminds me of an issue raised in the “Accomodationist and Proud of it” series. The issue is whether God can have or does have knowledge of all future contingents. If God does have this knowledge, and had it while creating the universe, we can have both options. The supposed problem, that foreknowledge means determinism, in my view rests on a misunderstanding. God can know what (to us) “will” happen in the future because God transcends time, not because the process is deterministic.


JKnott - #10394

April 20th 2010

That being the case, why not imagine that God had, as it were, all possible universes (including not only the original states but all subsequent states, even ones that were not determined by previous ones) in his mind, and decided to create this one because in this universe humans evolve. That would mean that God intended humans to exist, but that this intention is not a contradiction with the randomness of evolution. We are, therefore, both a mistake and God’s intention.


beaglelady - #10411

April 20th 2010

JKnott,

Mutations are random but evolution/natural selection are not.


Roger D. McKinney - #10416

April 20th 2010

This was very interesting is good evidence for evolution. I don’t think any creationist would argue that there is no evidence for the theory of evolution. This information is not new to creationists, and obviously it contradicts creation science, so how do creationists deal with it?

1) While evidence for evolution, it’s not the whole story. The evidence on both sides is much larger. One set of evidence does not validate a theory, or invalidate the other.

2) While the theory of evolution would predict such similarities in genetics, it does not invalidate creation science because nothing in creation science requires God to use completely different genetic material for every animal.

3) Genetic data are only available for the present, and fossil records are sporadic and less reliable. Thus, a phylogenetic tree is based on a hypothesis of the order in which evolutionary events are assumed to have occurred.

4) The mechanism for transmitting genes is missing. See Sanford’s “Genetic Entropy.”


Mike Gene - #10417

April 20th 2010

JKnott is entirely correct.  I would however make a slight, but important, modification.

That would mean that God intended humans to exist, but that this intention is not a contradiction with the randomness of evolution.

Exactly, except it goes a little deeper.  God did not merely intend “humans” to exist.  He intended JKnott, Bilbo, Darrel, and yours truly to exist.  Yet each one of us, and every one else on this planet, exists because of a choice our parents made and because of the randomness inherent in a particular sperm finding a particular egg.  Are we to believe that if God intended us to exist, we should be able to find scientific evidence of God guiding our parents to meet, of God guiding our parents to have sex at a precise moment, and God guiding the right sperm to the egg?  Really?  I think not.


Mike Gene - #10418

April 20th 2010

Hi Argon,

Well, that’s the death knell for ‘The Biotic Message’ hypothesis…

Agreed.


Jim - #10429

April 20th 2010

JKnott - #10393

Your question is too hard for me. 

It involves discerning such profoundly deep layers of causation (for verification or falsification), that I wouldn’t know the working/operational difference between where God’s omniscience (as prediction) ends and where God’s omnipotence begins in space-time interventions in cases where God decides to act on contingencies.

Evolutionary theory defines randomness as any mutation – whether in stochastic events or at germline regions somewhat predictably responsive to environmental pressures– that’s not beneficial to the needs of the organism. No matter how we define and re-define “randomness” (random v. constrained, random v.  distributed, random v. directed, and on), or even if we drop the word “randomness” from the lexicon, the ugly reality of non-beneficial change has theodicy written all over it. 

I’m not competent in sufficient precision (I think it would take infinite precision) in discerning deep levels of causation.  Under your hypothetical, I’m exceedingly incompetent at knowing where God’s predictive knowledge ends and where God’s action-based-on contingency begins.

Fun question.  But way over my head. 

Cheers,

Jim


John VanZwieten - #10434

April 20th 2010

Roger (or other YEC could offer help, too):

As I understand the current YEC position, all current dogs/wolves, etc are descended from one “proto-canine” pair that would have been on the ark.  Would YECs use the line of genetic reasoning from this post to study how we got wolves, coyotes, wild dogs, domesticated dogs, etc.?

I’ve heard the above about dogs, but I’m not sure the YEC position on primates.  Was there just one pair of “proto-primates” on the ark from which all current primates are descended?


Roger D. McKinney - #10438

April 20th 2010

John VanZwieten, I haven’t seen any material on the subject lately, but I would guess that primate is two large a grouping. YEC’s don’t have any problem with speciation, just the creation of new types of animals. If I’m using the terminology correctly, I think the objection would be about species evolving into a new genus.


Jim - #10439

April 20th 2010

Mike Gene - #10417

Yeah.  After the sperm and egg scenario, I ponder simple food intake as a function of growth between birth and maturity. 

For food-intake (“f”) and time-frame to maturity (“t”), what’s the relationship between f, t, and trajectories for individual growth? 

A stochastic process can have direction in growth with different trajectories through the space for different single organisms.  Body growth at time t+1 works as a function of body size at time t plus food intake at time t. Assume food availability has a probability distribution (randomness is involved).  Organisms in a population which put the same effort into finding food do not gain identical benefits in food intake.

Yeah, yeah, those who gathered a little manna had enough. 

And those who gathered a lot of manna had—a lot. 

But whether manna is gathered in quantities of enough or a lot, I don’t buy the idea that with enough maths alone (redefining or defining-away randomness), we can have evolution without any world in which it evolves.

It’s not quite way-cold down here.  Just way-messy.  Time for my cheeseburger.

Jim


Dennis Venema - #10440

April 20th 2010

Hi John,

You can see Todd Wood wrestle with some of the issues you’re asking about in his famous chimpanzee / human comparative genomics paper.

As far as I can tell (perhaps Joe Francis, who sometimes comments here can correct me if I am mistaken) Todd has rejected using comparative genomics to define original created kinds because genetic similarity for humans and chimps is closer than for other species claimed to be a “created kind” (e.g. felids, canines, etc).


JKnott - #10459

April 20th 2010

Mike—

Good point.  I agree.  That’s precisely what makes the old doctrine of exhaustive divine foreknowledge so useful.


John VanZwieten - #10493

April 20th 2010

Dennis,

Thanks for putting me onto that paper (which can be found here: http://www.creationbiology.org/content.aspx?page_id=22&club_id=201240&module_id=36954 )

I learned a new word, even: baraminology, which is the study of what constitutes original “created kinds.” 

I have to say in reading that paper I really feel for Todd Wood and his fellow creation-biologists as they struggle to reconcile science and faith.

I wonder how far he is willing to use comparative genomics to identify common ancestry.  Correct me if I’m wrong, but comparitive genomics is what dna testing is all about.  Maybe they just think it should be confined within a species to avoid uncomfortable conclusions?


John VanZwieten - #10498

April 20th 2010

Oh, and from this paper on baraminology: http://web.archive.org/web/20030618153040/http://www.creationresearch.org/crsq/articles/37/37_2/baraminology.htm

“Cats” and “dogs” each are a holobaramin—which is all related species from a created kind—which covers at least more than one genus and probably the entire families of felidae and canidae.  Chimps and gorillas together form a holobaramin, so other primates would have to be unrelated.


Robert - #10501

April 20th 2010

How can chimps and gorillas be a “holobaramin” together? Chimps are closer to humans genetically than they are to gorillas. To be consistent, you either have to include humans in the baramin (obviously unacceptable to a YEC) or have chimps and gorillas as each individual, unrelated created kinds.

I too feel rather sorry for Dr. Wood as I see him desperately strugling with the data that he obviously understands the implications of. I mean he recognises that “common design” is little more than an ad hoc response, but what other explanation will they ever come up with? He has to believe God created these patterns in organisms de novo, so what else can you really say apart from “well I guess God just made it that way?”


John VanZwieten - #10504

April 20th 2010

Robert,

Here are the guidelines for how “holobaramin"s are determined in order of importance, from that article:
1. Scripture claims (takes care of humans, maybe a couple others)
2. Hybridization—what can mate
3. Ontogeny (development from embryo to adult)
4. Lineage
5. Morphology and physiology
6. Fossils
7. Ecology


Argon - #10542

April 20th 2010

Karl A: “Argon (#10368), could you expand?  I looked up the book on Amazon, but that was about it.”
(Regarding the death knell for ‘The Biotic Messsage’)
Hi Karl,

The take-home claim in ‘The Biotic Message’ is that life, and the history of life were specifically designed to look unlike the products of evolution. Gert Korthof maintains a really nice collection of book reviews related to evolution and related controversies. A review of ‘The Biotic Message’ is here (http://home.planet.nl/~gkorthof/kortho41.htm) and does better justice to the explanation that I can manage in this limited reply space. Check also some of the archives of the ASA* evolution topic listserver.

*American Scientific Association.


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