Question on chromosome fusion and fertility

I’ve been idly wondering about this recently, and some digging around to see if this exact topic has come up here before turned up nothing, I saw that there are some professionals in the area of genetics posting here, so I might get a useful answer.

In cases where two chromosomes fuse, for a time the individuals with the composite chromosome are still a small part of the overall population with the unfused chromosomes. When a composite chromosome individual reproduces with a unfused-chromosome individual, could there be a mechanism in the offspring where the pairing off of the chromsomes during mitosis or meiosis could catalyze the unfused pair of chromosomes to fuse to match the composite chromosome? Allowing the process of moving a population towards all-composite individuals to be sped up?

Yes. It’s a common misconception that differing number of chromosomes is a barrier to hybridization, which is odd since the most common hybrid for us is the mule and the horses and donkeys have different numbers of chromosomes. Now, mules are almost aways sterile and this is often the result when the chromosomes of the parents are mismatched in number, but it isn’t always the case.

As you might know, our Chromosome #2 is the fusion of two “ape” chromosomes.

No, you misunderstand the question. I’m saying that when the paired chromosomes align with their counterparts during mitosis or meiosis, could (something) catalyze the pair of unfused chromosomes aligned with the fused chromosome to themselves fuse to match the already fused one? So that at the end of the cell division, you are left with two fused chromosomes, not one fused and two unfused?

Mitosis is not a problem. In mitosis, whatever is there just gets copied, the homologous chromosomes do not align with one another. Meiosis is where the problem arises, so a bit of background:

Consider 3 generations, call them G for grandparents (4), P for parents (2), C for child.

All human cells except sperm and eggs are diploid, with two non-identical copies (homologs) of each chromosome. Each P previously inherited two homologous copies of each chromosome, one from each G.

Meitoic recombination occurs in P’s sperm and egg cells. P’s two homologs align and a carefully orchestrated process of recombination occurs, where the DNA strands are cut and crossed over, resulting in new chromosomes each of which is a cut-and-spliced mosaic of the two G homologs present in P. Sperm and egg cells are haploid - they get only one copy of each recombined chromosome. The crossing-over is random, so each sperm & egg has a different mosaic mixture of the two G homologs. For meiotic recombination to occur, the karyotype must be identical. Thus, a horse P can generate viable sperm & eggs, because both G were horses with identical karyotype (64 chromosomes), so recombination can occur. Similarly, a donkey P can generate viable sperm and eggs, because both G were donkeys with identical karyotpe (62 chromosomes).

The two P’s mate, and upon fertilization the single copy of each chromosome in the sperm and the single copy of each chromosome in the egg just come together in the zygote. There is no alignment required at this stage, and not even any copying of DNA. So if one P is a horse with a karyotype of 64 chromosomes, and one P is a donkey with a karyotype of 62 chromosomes, that doesn’t present any problem per se at the level of the molecular machinery. C is a mule zygote with 64 horse chromosomes (each a mosaic of 2 G horse chromosomes) and 62 donkey chromosomes (each a mosaic of 2 G donkey chromosomes).

Mule zygote C’s cell can now proliferate to develop into a mature organism. The DNA copying in mitosis does not involve any alignment of homologs, just copying of what’s already there, so again the uneven number of chromosomes does not matter at the level of the molecular machinery per se.

But the problem arises in generating sperm or egg cells in the mule C, when meiotic recombination (as described above) is attempted. At this stage, the uneven numbers of chromosomes cannot all find a partner to match up and recombine with, and meiosis fails. It fails because the process of aligning and cutting and splicing homologous chromosomes involves carefully orchestrated and highly complex molecular machinery, with many careful checks and balances, and it generally won’t just “make do” - if things don’t look just right, it won’t complete successfully. Thus, mules cannot produce viable sperm or eggs.

I’m going to post this, then come back to answering your specific question.

Female mules, on rare occasions, have produced viable offspring when mated with a horse. We have a few geneticists on this MB. I’ll PM one or two and ask them to come and comment on the OP.

So, if you followed the background I gave above, I can begin to address your question:

In mitosis, there is no alignment of DNA, so what you described will not be relevant. Mitosis just copies what’s there.

Now for meiosis:

As I described, when the karyotype is substantially uneven as in a sterile mule, meiosis just fails to complete. That’s because the recombination process of alignment, cutting and splicing DNA requires carefully orchestrated complex molecular machinery, with many checks and balances, and if things are not going just right, it will usually just fail rather than “make do”. [ ETA: I see JM notes that it does on rare occasions succeed - which is typical of biology, never say “never”.]

However, you’re not describing a mule. You’re describing a situation where the two genomes as a whole are identical, with the sole difference being that two chromosomes are fused in one copy but not the other. Here, it seems much more plausible that meiosis might complete with reasonable frequency, since everything at least has something that it can precisely align with. My guess is that the atypical topology of the structure that would result from a fused chromsome aligning with two homologous but unfused chromosome might sometimes resolve successfully and sometimes fail. However, the process would not really occur in the way you describe, since meiosis results in mutiple haploid (single copy) sperm or egg cells, not diploid (two copy) cells. It would simply be a question of whether meiosis could complete successfully, and if it did probably some of the sperm or eggs would contain a single-copy fused chromosome, and others would contain two sinlge-copy unfused chromosomes.

I am one :slight_smile:

To add: since, as JM pointed out, there have been chromosome fusions over evolutionary time, it must be true that fusion mutations have sometimes passed down the germline into viable offspring in a background population that lacks the fusion. That doesn’t tell us much about the frequency of such events, though.

There’s a lot of literature on the evidence that human chromosome 2 is a telomere fusion, but I don’t know if there’s anything on how frequently telomere fusion mutations occur, or how and how easily they are then passed on in the germline. I’ll take a look.

Oh, OK. You’re kind of new, and I didn’t know that. Good to know going forward!

I’m studied math at college but messed around an almost dropped out; went back into science later in life, went into molecular biology & genetics. So I’ll bullshit my way through math, cosmology and other stuff that I’m interested in, but not very good at. I have more of what might approach “expertise” in molecular biology & genetics, although I’m retired so not completely current.

So with that wacky-ass Russian scientist that wanted to breed women with chimps, is that possible since chromosome 2 is a fused copy of two of the chimp chromosomes?

Yes. Chromosomes pair up only during prophase I of meiosis, and pairing is mediated by sequence similarity. Pairing between one fused chromosome and two unfused chromosomes is certainly possible - therefore, a hybrid individual should be perfectly capable of producing healthy offspring. Mitosis is a non-issue, because homologues don’t interact with each other then.

We don’t know for sure if humans and chimpanzees are interfertile - thankfully. But the chromosome fusion would present a minor issue. Far more important would be the accumulated evolutionary changes in the sequences of various genes.

Since none of the replies have addressed my actual question, I must still not be phrasing it clearly. It isn’t about “can chromsome fusions happen at all” or about “can fused and non-fused individuals produce viable offspring.” It is a very specific question.

Assume an organism that has inherited from one parent a single chromosome fused from two, and from the other parent two unfused chromosomes, and that both sets of DNA are essentially identical other than at the point of fusion.

During prophase I of meiosis (thanks for refreshing my mind on that detail) the chromosomes line up. Is there a possibility that this alignment bringing not only the 1 fused and 2 unfused chromosomes in alignment,* but also the two unfused chromosomes aligned end to end* lead to some mechanism “gluing together” the two unfused chromosomes so that there are now two (virtually) identical fused chromosomes and not one fused chromosome and two unfused ones? Possibly some DNA repair mechanism “noticing” the difference between the two, “assuming” a break, and “fixing” it? Sort of like (as a rough analogy) prions causing a conformation change in “normally” shaped proteins?

I took the trouble to answer your question quite thoroughly above in posts #4 & #6. It can’t just be answered in a couple of sentences: you need to read and understand the background I gave, because you don’t understand meiosis. It is a misconceived question.

In summary: alignment only happens in meiosis (not mitosis), and meiosis does not produce dipoid cells. The result of meiosis is haploid sperm and egg cells. So, if meiosis completes under the circumstances you describe (and I think it will, at least some of the time), the result will be haploid sperm or egg cells with either the singe-copy (haploid) fused chromosome or the single-copy (haploid) unfused chromosomes.

ETA: there’s a typo there, should read “meiosis does not produce diploid cells”

I am not trying to get into an argument here, but I understand your post, you do not understand my question. I’ll try rephrasing my question yet again.

Scenario 1–cell has one fused chromosome, two unfused chromosomes and nothing changes. At the end of meiosis, the result is one gamete with 1 fused chromosome and 1 unfused chromosome.

Scenario 2–cell has one fused chromosome, two unfused chromosomes, and some repair mechanism–triggered by seeing the fused chromosome as “correct” and the two unfused chromosomes as “broken”, patches together the two unfused chromosomes to produce a fused chromosome matching the first one. At the end of meiosis, the result is two gametes with 1 fused chromosome.

All I’m asking is if there is a mechanism where this is possible (and thus would speed the spread of the fused chromosome in a population.) You have not addressed that question (even to just say “no.”)

You need to understand what diploid and haploid mean:
All cells in your body except gametes are diploid - they have 2 homologous copies of each chromosome, one from each parent.
Gametes are haploid - only 1 copy of each chromosome.

Meiosis starts with a single dipolid cell, and actually generates 4 gametes. DNA is duplicated, then alignment and recombination occur, then the cells splits into 4 gametes, each with a single copy of each chromosome.

Again, gametes are haploid. If meiosis proceeds successfully, they will EITHER have 1 fused chromosome OR 1 unfused chromsome, not both.

I’d suggest that you go through one of the many graphical descriptions of meiosis to be found on line to learn more if you still haven’t got it. Since your Scenario 1 shows that you don’t understand meiosis, I’m not going to try to pick apart what you might mean in Scenario 2, it’s kind of a waste of time. It’s just a poorly conceived question at the moment.

Alternatively, explain why you’re asking this, and I’ll try to help.

Riemann, just forget it. You really don’t understand my question no matter how carefully I phrase it, and there is no point at us continuing to have two separate conversations that do not overlap.[URL=“Straight Dope Message Board - Your direct line to thousands of the smartest, hippest people on the planet, plus a few total dipsticks.”]

And (because nobody can say I’m not stubborn) I made this quick and dirty illustration for the question. All I’m asking is, could this in theory happen?