Does human 46 chromosomes in stead of great apes 48 point to a bottleneck?

Do human 46 chromosomes, instead of the great apes 48, point to a bottleneck in human evolution?
I assume that the human chromosome 2 is a result of a fusion of two chromosomes, orangutang, gorilla and chimpanzee all have 48 chromosomes.
I also assume that this fusion had happened ones and spread.
Literature seems to indicate that the chromosome fusion didn’t happen at the Chimpancee - hominin (human) split, but later during hominin (human) evolution, see eg Poszewiecka et al (2022) ‘Revised time estimation of the ancestral human chromosome 2 fusion’. Which explanation is more likely to have happened?

  1. A bottleneck from a supposed couple that are the first to be homozygote with the newly fused chromosome 2.
  2. It is more likely that the same couples genotype (new chromosome 2) slowly will spread in a larger population until everybody has 46 chromosomes.
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It’s (2), except for the part where you say ‘same couple’. It’s very unlikely there would be such a ‘couple’, since the fusion happens in an individual.


The offspring of the individual in which fusion had happened could (the most) be heterozygote for chromosome 2. But it is not unlikely that there would be such a couple, it is something that has to happened. See e.g. pedigree in Stankiewicz Molecular Cytogenetics (2016) 9:72 DOI 10.1186/s13039-016-0283-3.

My question is if it is likely that an altered number of chromosomes could spread in a population or if it is most likely a founder effect.

The only way to get a couple with 46 chromosomes is for the initially heterozygous fusion to spread tlhrough a population, achieving a high enough frequency that two heterozygotes would mate; assuming simple Mendelian genetics, 1/4 of their children would be homozygotes. In order to make it likely that two unrelated homozygotes would meet, the frequency of the fusion must be very high. So no need for a bottleneck, and anyway to set up the conditions for one the fusion must have previously spread through the population. That is, your second scenario would be a necessary precursor to your first. Nor would it be likely to cause reproductive isolation, whether in heterozygous or homozygous form.


Dear John

Two comments. 1. During the discussed fusion will you lose the parts of the two ‘old’ chromosomes that are distal to the fusion point, with possible gene loses. I have not seen any data of what, if any, genes are located there in today’s chimpanzees or gorillas. The new chromosome 2 will also move genes that earlier were in proximity to telomeric regions away from the effects of heterochromatin. One could expect upregulations of these genes. So, the fusion could have phenotypic effects. You may not need to only rely on ‘simple Mendalian genetics’.

Comment 2. The heterozygote state is an individual with 47 chromosomes, this result in an increased number of non-viable gametes during meiosis. The question is if this barrier is so big that it is more parsimonious to postulate a founder effect? According to ‘Ayala, F. J., and M. Coluzzi (2005) “Chromosome Speciation: Humans, Drosophila, and Mosquitoes.”. P N A S’ ‘Robertsonian fusions may play a role in speciation.’ If hybrid-dysfunction is true it could be tested through suppressed-recombination models. In Hybrid-dysfunction are the hybrids ‘underdominant’ and will eventually lead to complete reproductive isolation. These models were tested on the human, Drosophila and Malaria mosquitoes chromosomal rearrangements as cause for speciation. See also ref 11 and 12 in Ayalas paper as interesting papers were chromosomal rearrangements cause speciation.

I don’t think any significant genes were lost during the fusion, as it occurred in the telomeric regions at the very distal tips of the “old” chromosomes.
The two most distal (named) genes on chimp chromosomes 2A and 2B are PAX8 and RABL2A. These are both present either side of the fusion site on human chromosome 2.

The “old” chromosomes are acrocentric, while human chromosome 2 is metacentric.

Does that help?

@evograd has answered this one.

It will, but it turns out that it doesn’t significantly lower fecundity, as there are plenty of good gametes to go around. There are many extant mammal populations in which similar chromosomal polymorphisms are at fairly high frequency. Ayala, you will note, is talking about a whole series of chromosomal mutations by which humans and chimps differ, not must the chromosome 2 fusion. There’s no reason to suppose that one, by itself, to offer significant isolation.

I picked up Coyne’s book on speciation a while ago and was hoping to learn something about this, but I didn’t see much and in the process I learned that Coyne’s book on speciation is over my head. But a question: I’ve heard it said that chromosome count differences CAN lead to significant isolation. Are there particular sorts of fusions that are more prone than others to lead to isolation? I seem to recall that someone claimed that different chromosome counts will impair recombination, with a resulting tendency for the fused and non-fused chromosomes to diverge, and for this divergence to lead to reproductive isolation. But I may have misunderstood, or the fellow may have been mistaken, or some such thing. Anything you can enlighten me on here?

What would cause real problems would large inversions or transpositions, anything that tends to leave gametes with either too many copies of some genes or with none. As would anything that would result in anomalous pairing during meiosis. But a nice acrocentric fusion does none of that.



Both are possible, and I’m not sure which one is more likely. One peice of information we don’t have yet is good population-level statistics in the relevant time that might show what proportion of individuals (over time) had the fusion vs. did not. That might give some insight into how much genetic isolation there was about 700 kya (when the fusion likely arose).


I’m not sure.

It seems to depend how much genetic interference there was between fusion/non-fusion populations. I’m not aware of much hard data, but I have read some papers that argued that the interference might have been high.

Related to this is whether or not there was any large functional changes associated with the fusion. As I recall, that’s an open question as well. If there were large functional changes (e.g. in cognition) causally associated with the fusion, there might have been behavioral separation too. Once again, this is hard to test directly, and appears to be an open question.

What do you mean by a “fusion population”? How would such a population arise if there were significant interference (by which I think you mean reproductive isolation) between individuals with fused and unfused chromosomes? Remember that this condition would initially be heterozygous, and heterozygotes would have to attain a fairly high frequency in the population before fusion homozygotes would start showing up at all.


Nice to see your comments evograd! Have you found sequence that are distal (in Chimpanzee chromosomes) to the breakpoints of the new chromosome 2 (in humans)?

The fusion in chromosome 2 is a Robertsonian fusion. Ayala mention this type of fusion as ‘may play a role in speciation’. From the Drosophila - Hawaiian result, we see mainly inversions as causes for reproductive isolation (Carson, H. L. (1982) ‘Evolution of Drosophila on the newer Hawaiian volcanoes’, Heredity , 48 (1), 3—25). Which seems to be underlined by hole genome sequencing (Drosophila 12 Genomes Consortium* (2007) Evolution of genes and genomes on the Drosophila phylogeny, Nature (450) 203-18). In Morabine Grasshoppers we can see many examples of chromosome fusions. ‘The evidence thus strongly suggests that in these cases chromosomal rearrangements have played a primary role in generating genetic isolating mechanisms’. And under ‘Conclusion’: ‘The question we set out to answer in this article was whether the evidence from animal cytogenetics suggests or proves that structural chromosomal rearrangements sometimes (or frequently) play a decisive role in speciation. There is no question of their invariably doing so-the evidence of homosequential species in Drosophila excludes this possibility. But even if they do so sometimes, their precise role needs to be defined. One possibility is that certain types of rearrangements (different types in different groups, depending on the relative strength of the various kinds of restrictions discussed earlier) may generate de novo genetic isolating mechanisms, based on hybrid sterility, and hence tend to initiate speciation, even if the isolating mechanisms are at first only 5 or 10 per cent effective.’ (White M. J. D. (1969) ‘Chromosomal rearrangements and speciation in animals’, Annu. Rev. Genet. (3) 75-98).
In heterozygotes with 2n=27 you have at least 50 % non-viable gametes. The question is what effect this have. Maybe none without a phenotypic change and maybe allot with a phenotypic change.
What we see today is that humans 2n=46 and chimpanzee 2n=48 respective horse 2n=64 and donkey 2n= 62 givs non-viable / sterile offspring, but then a number of inversions (9 pericentric inversions in the human-chimp) and other mutations have been intruduced.

I agree!

I agree

But not in the particular case of hominids, which is what we’re supposedly talking about. Nothing you say there seems relevant.

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The population with the chromosomal fusion (or without it)

It’s hard to have any sort of discussion when you persist in replying with ambiguous one-liner sentence fragments. And it’s impossible on the basis of this nugget to imagine what scenario you are proposing. But are you considering that in order for there to be a “fusion population”, the mutation, originating in a single, heterozygous individual, must somehow reach a quite high frequency in that population? How could that happen if there were any serious difficulty in interbreeding?