Missing two chromosomes but doing fine. A partial karyotype of a man with 44 chromosomes.

A doctor from China contacted me through this blog with some exciting news. He had found a patient with 44 chromosomes instead of the usual 46. And the patient was perfectly normal as far as anyone could tell.

The doctor contacted me because the story of how this patient ended up with 44 chromosomes mirrored my story of how humans may have gone from 48 to 46 chromosomes a million or so years ago. The idea that human chromosome reduction could happen this way was theoretical when I wrote about it. Now we have living proof that it can and does happen.

Sticking Two Chromosomes Together

At first it might seem weird that losing a couple of chromosomes had no real effect on the patient since losing even one is usually fatal. But his case is different because he didn’t really lose two chromosomes (and all of their essential genes). Instead the chromosomes ended up stuck to two other chromosomes. So he has the same genes…they are just packaged differently.

When this happens with a single chromosome, it is called a balanced translocation. These are more common that you might think with about 1 in 1000 people having one.

The way to end up with 44 chromosomes like our patient requires that both parents have the same balanced translocation. The only way this is at all probable is if the parents are closely related. In this case, they are cousins.

I won’t go into the details (click here to learn more) but these parents had a 1 in 36 chance of having a child with a double balanced translocation. And this is our patient.

From 48 to 46 to 44?

As I said before, a big reason why this is all so interesting is because it provides confirmation of one way that humans may have gone from 48 to 46 chromosomes so many years ago. The first step might have been similar to what happened to our patient. Two closely related parents with the same translocation have a child together that has fewer chromosomes.

Back then, chromosomes 12 and 13 fused together to create what we now call human chromosome 2. The fused chromosome then slowly spread through the community. And then, for some reason, the group of humans with 46 chromosomes eventually supplanted the group with 48.

We can’t know for sure, but this may have happened through some random event where the 48 chromosome humans were mostly wiped out and the humans with 46 chromosomes were spared.  Humanity has nearly been wiped our before with the most recent case being a volcanic eruption 75,000 years ago.

If something similar happens in the future, I wonder if people will be questioning our close relationship to chimpanzees. “How could chimpanzees be our closest relatives,” these future folks might ask, “when we have four fewer chromosomes than they do?”  This assumes, of course, that the number of chromosomes has not changed in chimpanzees by then…

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22andHim 1 March,2010Dr. Barry Starr

  • Bo Wang

    I am glad to see it!

  • John Fiorentino

    “How could chimpanzees be our closest relatives,” these future folks might ask……”

    Ken Miller may like to try and answer that one.

    And with a 1 in 36 chance of producing offspring, how odd that it would be this group which managed to overtake the 48 ers.

    Makes ya think a little about our supposed relationship to the great apes. No?

  • 1 in 36 isn’t so bad…that is like flipping a coin and getting heads 5 or 6 times in a row or about the same as being dealt three of a kind or better in poker. And the odds are actually a bit better than that.

    The odds that a live birth will have the two chromosomes is closer to 1 in 9. About the same as having three kids who all end up being the same sex or of a woman in the U.S. owning a firearm.

  • John Fiorentino

    Nothing like apples and oranges Barry.

    Stats are fun, but can be misleading — in some cases even worse.

    In any event, you really didn’t address my points.

    But I kinda like you anyway.

  • travis stillson

    Interesting article, but if all the conjecture were removed all that is left is confirmation that two closely related humans will produce another human, and the human offspring can possibly end up with one less set of chromosomes. That is indeed an interesting find, but what I believe should be noted is what the offspring was. In this case, it is a human. Since this is what has actually been observed; why should we imagine that the fusion of two ape chromosomes could possibly produce anything other than an ape ? If there is any scientific evidence that this could actually happen I would like to know about it. Or, for that matter, why not take two chromosomes from anything, fuse them, and see what the result is ? My prediction is that the offspring would be the same thing as the donors of the four original chromosomes, just as this article reveals to us. Thank you !!

    • Barry

      When I wrote this blog, a big controversy was how humans and the great apes could have come from a common ancestor when the apes have 48 chromosomes and humans have 46. The feeling among many was that such a thing could not happen because of conditions like Down syndrome that come from having too many or too few chromosomes. This was even though it was pretty well documented in the animal world (wild mice are a great example). So here was a human example where without and effect on the person, chromosome number could be reduced from 48 to 46. The only conjecture is how the 46 then spread. Some of the data I have seen suggest that the fusion happened around one million years ago. This is probably too late to explain human/chimp differences anyway since we shared a common ancestor around 6 million years ago.

      If we fused chromosomes from more distantly related animals, the poor hybrid would almost certainly die straight away. Genes are arranged differently on different animals’ chromosomes…if the animals are too distantly related, the “child” would end up with too many of some chromosomes and too few of others.

      • I disagree that the only conjecture is “……..how the 46 spread”. I would argue that….”Back then, chromosomes 12 and 13 fused together to create what we now call human chromosome 2,” is also conjecture because there is no possible way know if there ever actually was a fusion at all. I would further argue that the claim of a fusion is assumed to have happened based on the assumption of common ancestry which is based on the assumption that similarities between organisms is evidence for common ancestry which is based on the presupposition that the diversity of life today ultimately came from a single celled molecule 3.8 billion years ago.

        What is the evidence that would support the idea that 2 chromosomes fusing, in any given sort of living thing, would ever produce anything other than what the donors themselves are ? I would argue here, that the best evidence of what would really happen is seen in the patient from China. In this case the fusion is absolutely known to have happened and the result was still human because he still had all the same genetic instructions to make a human. Evidence would have to be provided that natural, random processes could absolutely change the genetic instructions that would build a different kind of fundamental structure. Such as bird, dog, person, cow, etc. I’m not talking about the species level.

        In response to, “Some of the data I have seen suggest that the fusion happened around one million years ago.” And, “…..we shared a common ancestor around 6 million years ago.
        How did they arrive at this conclusion ? Was it by molecular clock and morphological similarities ? Thank you !

        • Barry

          The evidence is very compelling that chromosome 2 is a fusion of chromosome 12 and 13. The strongest evidence is taking a good hard
          look at all three of the DNA sequences and comparing them. When we do this, it becomes pretty obvious that chromosome 2 is a fusion of 12 and 13. Monica did a great job explaining this at http://genetics.thetech.org/ask/ask264

          You are right that none of us was there to see the fusion event happen but the DNA sequence shows that something like this almost
          certainly happened. I think about strong evidence like this in terms of key historical events. None of us saw the bubonic plague sweep through Europe in the 1300’s but the evidence that it happened is pretty compelling.

          As for the second point, I agree there is no evidence that the fusion caused the split by itself. Post fusion the person was
          almost identical to the people that came before. You could come up with something where for example, the fusion caused a DNA change that allowed the new person to speak or some such thing but there is no evidence that I know of that supports anything like that. It was more of a random DNA change.

          But one thing that it did do was make it so that the folks with 48 chromosomes would have had trouble having kids with the ones
          with 46. This type of isolation would mean that changes that developed in the two groups would not easily be transferred and so they would be free to develop separately. I am not saying this is what happened but it is another way that a chromosome fusion might spur a new species into forming.

          • I appreciate the article, but I would argue that the overarching theme, if you will, of it is the assumption that a fusion has indeed happened, whether by chance or design. Notice how it reads when you remove the two sentences that are describing the usual structure of a chromosome.

            Quoting Ms. Rodriguez, “What evidence do we have that two chromosomes fused to create human chromosome 2?……. “The very strong evidence to back up the fusion comes from the weird architecture of chromosome 2………”The easiest (and possibly only) explanation is that this happened because of the fusion of two chromosomes.”

            I would argue that “weird architecture” is not sufficient scientific evidence for a fusion. And, to argue that a fusion is “strong evidence” for a fusion is logically fallacious. She’s assuming what she’s trying to prove. Also, observing telomeres, and centromeres in, what would be thought of as, unusual positions is irrelevant since all chromosomes have telomeres, centromeres, etc. What would need to be taken into consideration is; what does the DNA inside those code for ? What do the instructions ,found in the DNA, that’s found in the Centro’s and telo’s, say to make ? There is enough information, now, about what these parts do, for us to know better than to think that simply lining up telomeres should lead to a new animal, since inside those parts reside instructions for reproducing itself.

            Quote, “This is exactly what we would predict for a chromosome fusion.”
            Was a chromosome fusion ever predicted previous to observing that chimp chromosome 12 &13, stacked on end, looked very similar to human chromosome 2 ?

            “But these sequences don’t look exactly like the telomere sequences we see at the ends of the chromosomes. These fusion telomere sequences have collected many DNA changes over time”……..”And the fact that the fusion telomere sequences have changed over time is even more evidence in support of common ancestry.”…….

            I would argue that the differences in those sequences is, at least in part, what accounts for humans being human, separate from chimps. If we do assume a fusion did happen, which we’ve seen could be possible based on the Chinaman, then the fusion would have to somehow change the genetic instructions to build something new. This last step cannot be demonstrated, scientifically, as being possible since, like the Chinaman, the newly fused chromosome would still contain all the same genetics as the parents, instructing for the building of a chimp. There is no reason to believe, based on what is known, that any new morphological instructions would result from a fusion. The gene can’t give what it doesn’t have.

            You had said, “Post fusion the person was almost identical to the people that came before.”

            Maybe I misunderstand your point here, but I thought that a chimp came before the (assumed) fusion. If the post fusion person is like the “people” who came before, then where is the chimp in this line ?

            Ms. Rodriguez says, “Common design predicts that DNA mutations have a purpose.”

            If by, “purpose,” she means to destroy life, she would be correct. But, from a (Biblical)common design perspective the designer didn’t put them there.

            Again Ms. Rodriguez, “It is difficult to see why a designer would make all of those changes and fuse two chromosomes together too.”

            Again, she’s merely assuming a fusion. Apparently she has it in her head that a fusion has in fact happened, even though there’s no way to support it scientifically, as you and I agree on, and can’t seem to even conceive of the possibility that it was just designed that way to start with.

            On a final note, to your statement regarding bubonic plague and the “fusion event”. The line of reasoning doesn’t follow because, even though you and I weren’t there to witness it, there were absolutely eye witnesses that confirm it happened. With the human chromosome 2 we’re looking at what IS, and assuming that it is the way it is, because of this or that reason, with no way to confirm it. Again, I would argue that the best indication of what would actually happen is the Chinaman case, because, not only that particular evidence, but what we know about the information, codes, instructions, and regulatory systems that’s packed into those gene’s. There is no scientific evidence that this kind of change can happen. Don’t get me wrong, I believe in evolution, but I haven’t seen any scientific evidence that supports the idea that the fusion of any number of chromosomes would produce anything other than that kind of animal or death. Thanks very much !!!!


Dr. Barry Starr

Dr. Barry Starr (@geneticsboy) is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA and runs their Stanford at The Tech program. The program is part of an ongoing collaboration between the Stanford Department of Genetics and The Tech Museum of Innovation. Together these two partners created the Genetics: Technology with a Twist exhibition.

You can also see additional posts by Barry at KQED Science, and read his previous contributions to QUEST, a project dedicated to exploring the Science of Sustainability.

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