The Rise of Human Chromosome 2: The Dicentric Problem

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This essay is the first of a series authored by Dave Wisker, a Graduate Student in Molecular Ecology at the University of Central Missouri.

Back in 2005, Casey Luskin wrote an article criticizing Kenneth Miller’s testimony at the Dover ID trial called “And the Miller Told His Tale: Ken Miller’s Cold (Chromosomal) Fusion”. Luskin took Miller to task for showing that the chromosomal fusion which resulted in human chromosome 2 was evidence for the common ancestry between humans and the great apes. His argument was ably taken apart by PZ Myers here and Mike Dunford here.

Luskin also wrote:

In other words, Miller has to explain why a random chromosomal fusion event which, in our experience ultimately results in offspring with genetic diseases, didn’t result in a genetic disease and was thus advantageous enough to get fixed into the entire population of our ancestors. Given the lack of empirical evidence that random chromosomal fusion events are not disadvantageous, perhaps the presence of a chromosomal fusion event is not good evidence for a Neo-Darwinian history for humans.

Both Myers and Dunford pointed out those heterozygotes for the type of chromosomal fusion in question did not necessarily have to suffer from genetic disease or infertility. But they did not discuss the plausibility of the fixation of the fusion in the human population. In a series of forthcoming essays I will examine this, and also address some other common ID/creationist ‘problems’ with the fusion not mentioned by Luskin. The first problem is:

The Dicentric Problem

ID proponents on human chromosome 2 sometimes bring up the fact that a telomeric fusion results in a dicentric chromosome, that is, a chromosome with two centromeres. The following illustration of a similar kind of fusion shows how a dicentric chromosome can come about:

dicentric.jpg

Since the centromere is the point at which the spindle attaches to the chromosome at mitosis and meiosis, wouldn’t having two centromeres result in the possibility of the spindle attaching at two points on the chromosome, pulling it apart? A common counterargument to this is that in many dicentrics, one centromere becomes inactivated, and, indeed, that seems to be the case in human chromosome 2. But doesn’t that mean we now need two mutations–first the fusion, then the centromere inactivation– to get a viable chromosome? Doesn’t that dramatically reduce the probability of the fusion becoming fixed?

Not necessarily. For a long time it was assumed all centromeres were pretty much alike, so it was also assumed that they were equally efficient at assembling kinetochores (the actual attachment point for the spindle). A 1994 paper by Beth Sullivan and her lab at Duke University suggests that not all centromeres are equal: centromeres from non-homologous chromosomes appear to assemble kinetochores at different rates. Thus, in a fusion between two non-homologous chromosomes, like that of human chromosome 2, one centromere begins preparing its kinetochores before the other, and by being able to do so may interfere with the other finishing (or even beginning) in time for the next phase of meiosis or mitosis. As the paper says in the abstract (my emphasis):

Approximately 90% of human Robertsonian translocations occur between nonhomologous acrocentric chromosomes, producing dicentric elements which are stable in meiosis and mitosis, implying that one centromere is functionally inactivated or suppressed. To determine if this suppression is random, centromeric activity in 48 human dicentric Robertsonian translocations was assigned by assessment of the primary constrictions using dual color fluorescence in situ hybridization (FISH). Preferential activity/constriction of one centromere was observed in all except three different rearrangements. The activity is meiotically stable since intrafamilial consistency of a preferentially active centromere existed in members of six families. These results support evidence for nonrandom centromeric activity in humans and, more importantly, suggest a functional hierarchy in Robertsonian translocations with the chromosome 14 centromere most often active and the chromosome 15 centromere least often active

By essentially ‘out-competing’ the other centromere, normal segregation of the chromosomes at meiosis is achieved, without requiring two mutations.

Reference:

Sullivan BA, DJ Wolff, and S Schwartz (1994). Analysis of centromeric activity in Robertsonian translocations: implications for a functional acrocentric hierarchy. Chromosoma 103(7):459-67

14 Comments

Not to quibble with an otherwise fine essay, but the cartoon would be pretty confusing if you thought it actually illustrated the text. The cartoon shows the fusion of two p arms of what appear to me to be metacentrics. Ignoring the placement of the centromeres, though, if this were a represenation of a Robersonian fusion between two acrocentrics, it would mean that both q arms are lost. This is not trivial, as the lost material from a fusion depicted in the figure would undoubtedly lead to substantial aneuploidy. AFAIK, there are few if any essential genes that map to the p arms of human acrocentrics; most of the genes are on the q arms. I would have drawn the centromeres closer to the upper telomeres, to better represent acrocentric chromosomes, and I would have placed the breakpoints above the centromeres.

Nevertheless, thanks for doing this.

Joel said:

Sorry for the double post.

Well, since I am an English teacher, I was glad to see it, because I rely on cartoons like that to make this kind of stuff understandable.

Doesn’t that dramatically reduce the probability of the fusion becoming fixed?

Reduce it from what, I have to wonder?

I’d think that fixation of this sort of thing probably is of rather low probability, else there’d be way more examples of it.

Besides, this fusion thing is only one of the pieces of evidence for common ancestry. It doesn’t have to prove the entire theory on its own, any more than does any other one piece of evidence. The anti-evolution activists do like to focus on each individual piece of evidence at a time; I guess they’re hoping that people won’t realize (or that nobody will point out) that acceptance of a theory is based on all of it taken together.

Henry

Joel said:

Not to quibble with an otherwise fine essay, but the cartoon would be pretty confusing if you thought it actually illustrated the text.

I agree, but I chose this more to illustrate how a dicentric chromosome could form.

Henry J said:

Reduce it from what, I have to wonder?

I’d think that fixation of this sort of thing probably is of rather low probability, else there’d be way more examples of it.

The argument from IDers and creationists is that the fixation probability is vanishingly small. I intend to show in later installments that this is not necessarily the case.

My theory of how to compute the probability of fixation of chromosome fusion:

Take number of known cases of a species that has one chromosome that is two in other species.

Divide by number of currently living species.

Multiply by 100% to get percentage probability.

Would that work?

Henry

@Henry: we don’t know either how many species have this kind of variation (which may be “all of them”) or how many species there are, and we don’t know how often such events arise, so, no, it wouldn’t work. You’d be calculating the probability of a species displaying chromosome fusions, not the probability of a given fusion becoming fixed.

This definitely constitutes winning by a Wisker.…

That I have not seen this discussed anywhere means this is probably a very silly question from a non-biologist, and my inferences are probably wrong for a multitude of reasons. However, I come here to get educated, so…

The first fusion of the two chromosomes, however it occurred, would result in production of a gamete with 23 chromosomes. If this met with a “normal” gamete, could a viable individual result, (carrying an essentially neutral mutation,) with one of the un-fused chromosomes attached to each of the two centromeres on the fused chromosome? If so, a mutant individual could then breed freely with 48 chromosome individuals, and centromere inactivation would not become an issue until the mutation had become common enough in a population to result in a significant chance of two mutants interbreeding to produce a true 46 chromosome individual.

Any beneficial mutation occurring only on the otherwise neutral fused chromosome would increase the chances of fixation.

A repeat of the “error” which triggered the initial fusing might be much more likely to result in fusion of the other chromosomes as their susceptible ends would be held in much closer proximity than in a normal cell.

Dave Lovell said:

That I have not seen this discussed anywhere means this is probably a very silly question from a non-biologist, and my inferences are probably wrong for a multitude of reasons. However, I come here to get educated, so…

The first fusion of the two chromosomes, however it occurred, would result in production of a gamete with 23 chromosomes. If this met with a “normal” gamete, could a viable individual result, (carrying an essentially neutral mutation,) with one of the un-fused chromosomes attached to each of the two centromeres on the fused chromosome? If so, a mutant individual could then breed freely with 48 chromosome individuals, and centromere inactivation would not become an issue until the mutation had become common enough in a population to result in a significant chance of two mutants interbreeding to produce a true 46 chromosome individual.

Any beneficial mutation occurring only on the otherwise neutral fused chromosome would increase the chances of fixation.

A repeat of the “error” which triggered the initial fusing might be much more likely to result in fusion of the other chromosomes as their susceptible ends would be held in much closer proximity than in a normal cell.

The issue regarding the prewsence of two centromeres is, if both are equally efficient at assembling a kinethochore (the point at which the spindle attaches), then there is the possibility that two spindle fibers will attach to the chromosome. If that happens, then at meiosis the chromosome could essentially be tugged apart in two directions, resultimg in an damaged gamete, and thuis negatively affecting fertility.

What Sullivan and her colleagues are suggesting is, one centromere is more efficient at assembling the kinetochore, and that this possibly interferes with the other centromere doing the same thing. The actual mechanism remains unknown, as far as I know.

Dave Lovell, I think that you’ll find a number of your questions answered at the two posts linked in the first paragraph. Another, more extreme example (with pictures!) can be found here. A famous example of this is the Przewalski Horse, which despite having 66 chromosomes, can successfully breed with normal horses, who have 64.

Dave Lovell said:

The first fusion of the two chromosomes, however it occurred, would result in production of a gamete with 23 chromosomes. If this met with a “normal” gamete, could a viable individual result, (carrying an essentially neutral mutation,) with one of the un-fused chromosomes attached to each of the two centromeres on the fused chromosome?

Yeah, I got to wondering about that myself. I traced back to the Pharyngula article by PZ Myers mentioned above and he did a bangup job of explaining it. If you want a tidied form I put a writeup on my message board:

http://gvgpd.proboards.com/index.cg[…]p;thread=116

Check the Wikipedia article on chromosome numbers. Wow, what wild variations! I’ll have to dig into this some more.

Cheers – MrG / http://www.vectorsite.net/gblog.html

I am confused.. and I’m no geneticist, so please pardon my ignorance, but I am studying as hard as I can.

Chromosome 2 was fused at point X, in genetic history, given and accepted. So it (chromosome 2) contains two centromeres of important data, right? Are there still two actual centromeres? In my opinion, there have to still be.

You mention that one centromere is deactivated but doesn’t it still have to have the second legacy chromosome’s centromere-worth of data for viability? I mean, because it’s inactivated, doesn’t it still allow for protein expression?

Please be gentle, sock-puppet and stick-figures very welcome.

Just_Tim: AFAIK the centromere is merely the place where the two chromatids (the paired chromosome strands) are attached to each other and where the spindle fibres attach. There is no coding DNA there. If attachments form at both centromeres I don’t think it would do much harm unless the spindle fibres were attempting to pull in opposite directions.

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This page contains a single entry by Arthur Hunt published on February 8, 2009 6:28 PM.

Science Gets Cut was the previous entry in this blog.

The Rise of Human Chromosome 2: The Fertility Problem is the next entry in this blog.

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