The Mystery of the Missing Chromosome (With A Special Guest Appearance from Facebook Creationists)

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[Note: This post ended being the first of a series of four.

There’s something fascinating about our chromosomes. We have 23 pairs. Chimpanzees and gorillas, our closest living relatives, have 24. If you come to these facts cold, you might think this represented an existential crisis for evolutionary biologists. If we do indeed descend from a common ancestor with great apes, then our ancestors must have lost a pair after our lineage branched off, some six million years ago. How on Earth could we just give up an entire chromosome.

A close look at our genome and the genome of our close relatives reveals that we didn’t. We just combined a couple of them. Every now and then, chromosomes fuse. This fusion occurs as sperm and eggs develop, as pairs of chromosomes fold over each other and swap chunks of DNA. Sometimes two different chromosomes grab onto each other and then fail to separate.

Scientists have observed both humans and mammals with fused chromosomes. Chromosomes typically have distinctive stretches of DNA in their center and at their ends. From time to time, scientists will find an individual that’s short a chromosome, but one of the chromosomes it retains now has an odd structure, with chromosome endings near the middle and other peculiar features.

This might seem like a fantastic mutation–something like a human and a horse being joined into a centaur. Remarkably, however, fused chromosomes are real, and there are surprising number of normal, healthy people carrying them.

If humans and apes did indeed share a common ancestor, then it would make sense that two chromosomes fused in our ancestors. The rise of genome sequencing allowed them to test that hypothesis. They found that human chromosome two bears the hallmarks of an ancient chromosome fusion, with remnants of chromosome ends nestled at its core. In 2005, it became possible to test the hypothesis again, when a team of scientists sequenced the chimpanzee genome and could compare it to the human genome. The chimp genome team were able to match human chromosome two to two unfused chromosomes in the chimpanzee genome.

Ken Miller, a biologist at Brown who was an expert witness in the 2005 Dover creationism trial, includes this research in his lectures on evolution. Here’s a video of one of those lectures, where he lays out some of the evidence with impressive clarity.

What makes evolutionary biology such a fun subject to write about is that it does not stay still. While Miller’s description is entirely accurate, the past five years have rendered it obsolete. Last month, Evan Eichler at the University of Washington and his colleagues published a study in the journal Genome Research in which they deeper into the history of our missing chromosomea study in the journal Genome Research in which they deeper into the history of our missing chromosomea study in the journal Genome Research in which they deeper into the history of our missing chromosome.

They were able to do so thanks to the publication earlier this year of the gorilla genome. A comparison of the human, chimpanzee, and gorilla genomes confirms that the ancestors of gorillas branched off from the ancestors of chimpanzees and humans about ten million years ago. Humans and chimpanzees then branched apart later. A comparison between all three species provides a clearer picture of what our chromosomes looked like before they fused, and how they’ve changed since.

Eichler and his colleagues put together a diagram to illustrate this ten-million-year saga, which I’ve adapted here.

By comparing human chromosome two to the unfused versions in the chimpanzees and gorillas, Eichler and his colleagues reconstructed the chromosomes in the common ancestor of all three species:

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The bands correspond to segments of each chromosome. The colors represent the two ancestral chromosomes (I’ll just call them green and red to keep from getting bogged down in confusing numbers). The hash marks represent regions of very unstable DNA. These areas, which are full of repeating sequences, are prone to accidentally getting duplicated, expanding the chromosome. They’re also where chromosomes are likely to trade chunks with other chromosomes. That’s why the red chromosome has a little green at the end. It had picked up part of the green chromosome earlier than the common ancestor of us, chimpanzees, and gorillas.

The green chromosome then changed:

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Three key events are illustrated here. First, the top of the green chromosome flipped (another common type of mutation, called an inversion). Then a chunk of yet another chromosome got stuck to the end of the green chromosome, marked here in pink. And then a new piece of DNA got stuck at the end of the green chromosome, known as StSat, and marked here as a yellow dot.

The ancestors of gorillas then diverged from the ancestors of chimpanzees and humans. They underwent some ten million years of independent evolution, during which time a lot happened. For one thing, the cap on the green chromosome got duplicated and pasted onto other chromosomes, including the red one, and even on the other end of the green one itself. In the illustration below, the yellow and pink segments, along with the adjoining green segment, are represented by a brown oval:

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Meanwhile, the ancestors of chimpanzees and humans were evolving. The two chromosomes continued to change, as shown here.

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A copy of StSat got glued to the end of the red chromosome, and then the pink and green segments at the top of the green chromosome got flipped.

The chromosomes at the right of the figure show you what our two chromosomes looked like before they got fused. When the human and chimpanzee lineages split, each lineage inherited them. And in each lineage, they evolved in a different way.

In the chimpanzee lineage, the chromosomes didn’t fuse. Instead, this happened:

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The caps on both the green and red chromosomes were duplicated massively and ended up on lots of other chromosomes.

And finally, here’s what happened to humans after our ancestors split from chimpanzees:

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The two chromosomes fused, and the cap was deleted, inclusing StSat. It could no longer spread around our genome, the way it did in chimpanzees and gorillas.

This study is an important advance in our understanding of how human chromosomes evolved–a subject of medical significance, too, since the duplication of the DNA at the end of chromosomes can cause dangerous mutations that can cause genetic disorders. Plus, it is very cool to see how our chromosomes are, in fact, an ancient patchwork.

It just so happens that I came across this paper by a very roundabout way–but an instructive one. Over at the Panda’s Thumb, I learned yesterday that biologist Nick Matzke was trying to set things straight on a creationist Facebook page. The page is set up by an outfit called The Biologic Institute, which is promoting a new book by two of its employees that purports to reveal all the flaws in the evolutionary account of human beings. They linked to a post on a site run by the intelligent design clearinghouse, the Discovery Institute, which provided some details from the book. It’s called, “A Veil Is Drawn Over Our Origin as Human Beings,” and it’s written by David Klinghoffer.

Matzke left several comments explaining why they were wrong, and what some of the evidence for human evolution actually is. The Biologic Institute didn’t take this well: they suddenly announced that Facebook was not the appropriate venue for debate, and would limit comments to 100 words, or maybe shut the whole thing down.

I found this deliciously ironic and had to jump in too. I pointed out that the site they linked to does not allow comments (which is fairly typical of creationist web sites). So there was no other way to ask questions than to post them to Facebook. And my question concerned fused chromosomes.

Klinghoffer declares:

The evidence from chromosomal fusion, for one, is strikingly ambiguous. In the Darwinian presentation, the fact that humans possess 23 chromosome pairs and great apes 24 clearly points to an event in which human chromosome 2 formed from a fusion, leaving in its wake the telltale sign of telomeric DNA — normally appearing as a protective cap at the end of the chromosome — in the middle where it doesn’t belong. Ergo, common descent.

But Casey [Luskin, of the Discovery Institute and co-author of the book] explains, there’s a lot wrong with this inference. Even if there was such an event and humans once had 24 chromosome pairs, it doesn’t at all follow that this happened in some prehuman past. Nothing stands in the way of picturing a human population bottleneck accomplishing the spread of a fused chromosome 2 from part of an early human community to all of it.

But the idea of such an event having occurred at all is itself far from sure. The telomeric DNA parked in the middle of chromosome 2 is not a unique phenomenon. Other mammals have it too, across their own genomes. Even if it were unique, there’s much less of it than you would expect from the amalgamation of two telomeres. Finally, it appears in a “degenerate,” “highly diverged” form that should not be the case if the joining happened in the recent past, circa 6 million years ago, as the Darwinian interpretation holds.

I was baffled, so I asked on Facebook for the evidence that the form of the chromosome wasn’t what you’d expect if it fused six million years ago.

What followed was a ridiculous runaround, some of which I’ll reproduce here:

Biologic Institute: Sorry, Carl, what link contains that particular quote?

Me: I am quoting from the page that YOU linked to.

Biologic Institute: Ah! That evidence is in the book that the post describes.

Carl Zimmer: In other words, the only way we can check these claims is to purchase the book? There’s no evidence published in peer-reviewed journals?

[No response]

Carl Zimmer: The book you are pointing us to is written by two Biologic Institute employees–the same Institute that puts out this Facebook page. Why can’t you describe your evidence about the chromosome fusion here?

[An hour passes. No response.]

Carl Zimmer: Hello? Is anyone there? Are you choosing not to respond to my request for evidence from your own book? How do you calculate what the chromosome fusion DNA should look like if it fused six million years ago?

Biologic Institute: Carl, you write books for a living. Do you rehearse their content on your blog for anyone who asks?

Carl Zimmer: Hello, Biologic Institute. If I make a strong claim about science in an online forum, and someone asks me for evidence for that claim, I do not say, “Well, you’ll just have to read my book.” I provide the evidence–I point to the peer-reviewed research on which I based my statement. But, hey, I’d be perfectly satisfied if you pointed me to a scientific paper that presents calculations showing that the chromosome fusion could not have happened six million years ago. I can go find it for myself–if such a paper actually exists.

Well, that was the last I heard from the Biologic Institute. They still haven’t piped back up on their own thread. However, I did hear from someone who had read the book, Paul MacBride. (He even reviewed it here.) Here’s the comment he left on Facebook:

Carl, I can tell you the answer to your question, as I have read the book. Luskin provides no evidence for this. Well, more correctly, he quotes a question from this paper “If the fusion occurred within the telomeric repeat arrays less than ∼6 Mya, why are the arrays at the fusion site so degenerate?” but not their three suggested answers. Luskin asserts that if a chromosomal fusion occurred it should have been a neat and tidy joining of the two chromosomes in question, anything else is a Problem For Evolution. Dave Wisker addressed this succintly in a comment at Panda’s Thumb

That paper MacBride mentions? It’s the 2002 paper I mentioned at the start, the one that presented evidence for fusion based on a study of the human genome. In other words, the authors of this new intelligent design book cherry-pick a quote out of a paper that’s ten years old (you can check for yourself, the paper’s free). That, it seems, is all the evidence they have. If anyone tells you how impressive the science is behind intelligent design, how superior it is to evolutionary biology, may I suggest you use this example to show them how wrong they are.

I read the 2002 paper long ago, but MacBride’s link led me to reread it. I also noticed that it was cited by a number of more recent papers, including Eichler’s new one. It just goes to show how you can end up learning something new in the most unexpected places.

Update #2: Actually, they’ll do a lot more–here’s my round up of the four days since I posted this.