"My family tree spreads wide as well. I am a great ape, and you are a great ape,
and so are chimpanzees and orangutans and bonobos,
all of us distant and distrustful cousins." ~ Katherine Applegate
Human Chromosome 2 Fusion:
The case of the missing DNA
Some History
As early as the mid 1800’s when the nuclei of eukaryotes (non-bacteria; we are eukaryotes) were stained, small condensed bodies were noted and called chromosomes, from the Greek meaning “color” and “body”. Because microscopes did not have high enough resolution, some scientists felt humans had 48 chromosomes rather than 46. It wasn’t until 1958 that the true number of human chromosomes was confirmed to be 46. Previously in 1953, many years of controversy regarding the molecule of inheritance was finally agreed upon when Watson and Crick published their famous paper proving that the instructions for inheritance was DNA. Before that many scientists including Linus Pauling thought that the DNA letters of ATCG were too limited to code for the complexity in life and they favored proteins instead as the repository of inheritance. Now we knew DNA in the chromosomes was the molecule of inheritance and humans had 46. Genetic studies of the other great apes in the early 1960s (chimps, bonobos, gorillas, orangutans) showed that they all had 48 chromosomes. Since science knew evolution was true and that we shared common ancestors with the great apes, how then did we end up with 46 chromosomes and evolve from all our common ancestors with 48 chromosomes?
Chromosome Basics
A chromosome is made up of DNA but also contains different compounds in addition to the DNA. The DNA is combined with proteins called histones that look like small balls in diagrams. DNA normally exists in an unraveled state that appears messy to our eyes. Think of a bowl of cooked spaghetti. When a cell divides and makes new cells the DNA is condensed down into small packets for easier moving. After duplication to make new DNA, the packages - called chromosomes - are lined up at a stage called metaphase and pulled apart with one set going into the new cell and the other set remaining in the parent cell. Note the chromosome below at metaphase and that there is a constriction in the pairs like a belt has been tightened called the centromere that will be discussed shortly. See Figure 1.
Figure 1. From nuclear chromosomes to DNA with bases exposed
When you look at chromosomes today microscopes and staining techniques have improved to the point where the banding patterns from various dyes result in stunning photos. When we compare human chromosomes to chimp chromosomes for example, the banding is almost identical. To the evolutionary scientist that’s because they share an ancestor. To the antievolutionist it’s only due to common design; since humans and chimps are both primates and very similar, a Designer in creating these two separate species would have of course used some of the same DNA according to them. To the antievolutionist, humans and chimps never shared a common ancestor. This is based almost entirely on creationist a priori religious beliefs in most cases. If you look at Figure 2 the only way to make all the human (H) and chimp (C) chromosomes match is to take chimp's 12 and 13 and stick them together end on end and now the banding of those two fused chromosomes match human chromosome 2. This is what was announced in 1991, that a fusion point that matches chimp chromosomes 12 and 13 had been found in human chromosome 2.
Figure 2. Fair Use applicable. For education purposes. https://www.kqed.org/quest/586/chromosome-fusion-chance-or-design
The Past Fusion of Our Chromosome 2
This discrepancy in chromosomes between humans and the other great apes theoretically initially presented a problem for evolution since it was settled science that humans evolved from a shared ape ancestor that must have had 48 chromosomes. It was not until 1991 that it officially was solved. A paper from Yale University School of Medicine (yes, evolution is necessary for modern medicine. See Evolutionary Medicine) showed what happened to the missing chromosome material; it was there all along, or more specifically the DNA. Human evolution from a shared ancestor with the great apes was vindicated by genetics and confirmed the fossil record.
To keep the numbering alignment working for the two species, chimp chromosomes 12 and 13 were renamed 2A and 2B in 2004. See Figure 3.
Figure 3. JW Schmidt. https://en.wikipedia.org/wiki/Chimpanzee_genome_project#/media/File:Humanchimpchromosomes.png
Now it gets interesting and the fusion shows that Evolution is a scientific theory because it can be tested and makes predictions, which means it can be falsified. And as a reminder, the Theory of Evolution has withstood 150 years of testing. Chromosomes have ends on them called telomeres that protect them when copying and moving around. These collections of DNA are called tandem repeats and are the sequence of TTAGGG and then the opposite on the other side of the DNA “ladder” would be CCTAAA. As we age telomeres become smaller and worn down and much research is ongoing into slowing that process down to help us with aging. So, telomeres should not be found in the middle unless the chromosome had become fused in the past. In addition there is a constricted area in the chromosomes best seen in metaphase before the chromosomes are pulled apart. This is where the cell attaches molecular “ropes” to pull them apart into the now two cells. And you can’t have two because that would cause the pulling points to attach at two points instead of one. So besides old telomeres in the middle of a chromosome there should be an old vestigial inactivated centromere that is no longer in use if there was a fusion. If humans evolved from a great ape ancestor shared with chimps that had 48 chromosomes, we should find a fused chromosome with telomeres in about the middle and a second dead vestigial centromere. Furthermore, by looking at chimps 2A and 2B when the ends are put together we can even see where the two centromeres should be. One is active in HC2 now, so we even know where to look to find a second inactive one! See Figure 4 diagram below of what happened and where we can look on HC2 for the evidence. Also look at figure 2 again and see where we can look for the evidence more specifically on HC2. Do you see that the inactivated vestigial centromere should be just below the active one that is presently in HC2?
Figure 4. SaudiPseudonym, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
As previously mentioned, in 1991 the area shown to be a fusion site was found to have the sub-teleomere sequences predicted and is located at 2q13 - 2q14.1 (the chromosome is divided into a top “p” and bottom “q” from the centromere). In 1992 the second vestigial centromere was located on HC2 where predicted at 2q21.3 - 2q22.1 . In 2005 the exact fusion point was sequenced. See Figure 5 and find the arrow which points to the exact fusion point. This sends shivers up my spine because we are looking at an event that happened millions of years ago in a single individual of our distant ancestors. And he or she spread that chromosome event through inbreeding first in a small population and then to all modern humans (and also Neanderthals and Denisovans).
Figure 5. https://i.imgur.com/CJRRUGo.png
To further confirm the findings, in 2006 Stefan Muller tagged HC2 with a dye and then applied the same dye tags to an orangutan's cells. See Figure 6. The HC2 photo is on the right and the orangutan chromosomes are on the left. Note that the tagged DNA is found in two human chromosomes 2 (we get one each from a parent) but 4 in the orangutan because the DNA is not in a fused state (chromosomes 12 and 13 in chimps) essentially proving the fusion observation in humans because there are four places with the same matching HC2 DNA in the orangutan as in the 2 locations in humans, exactly as predicted.
Figure 6. Human tagged karyotype on the right, Orangutan on the left.
From: Verena Schubel, Stefan Müller, Department Biologie der Ludwig-Maximilians-Universität München., CC BY-SA 2.5 <https://creativecommons.org/licenses/by-sa/2.5>, via Wikimedia Commons
Here is the explanation of his experiment: "DNA of the human chromosome 2 was labeled, applied to Orang-Utan (left) and human metaphase chromosomes (right) by fluorescence in situ hybridization and detected in green. While in the human metaphase spread only the two copies of chromosome 2 were detected, in the Orang-Utan metaphase spread the two original chromosome pairs were painted: Human chromosome 2 is the evolutionary derived fusion product from two separate ancestral chromosomes. In non-human primates - like for example in the Orang-Utan (chromosomes on the left side) - as well as in several other mammals, two chromosomes are observed which carry human chromosome 2 orthologous genes and syntenic segments of orthologous DNA sequences. The fusion in human 2q13-14 at approximately 114 Mbp of the human reference sequence (see Ensembl) occurred after the split of the human and chimpanzee lineages from that of their last common ancestor.”
Here is a short summary of the fusion and how it relates to human evolution. Also discussed is how an individual with this chromosomal number could reproduce and how that 46 number could become fixed in a small population and then spread.
Potential Objections
Various people have raised some observations that they perceive as negating the claim that HC2 is a fusion product. All of them have answers, however. HC2 is definitely a product of a fusion of an ancestor to humans, specifically what now resembles chimp's 12 and 13 chromosomes.
1. There is too much degradation in the fused telomeres was a common objection. This is discussed and dismissed along with some inversions that happened before the fusion in an online debate between the Discovery Institute and Carl Zimmer: https://carlzimmer.com/the-mystery-of-the-missing-chromosome-with-a-special-guest-appearance-from-facebook-creationists/ The Mystery of The Missing Chromosome
2. The DDXL112 gene in the fusion area. This and several other objections are addressed in an excellent 28 min video. https://www.youtube.com/watch?v=qVeriF1OL54&t=762s
3. The claim that there are numerous telomere sections throughout chromosomes so a fusion by noting telomeres in the middle of chromosomes is unjustified. Why there are short telomere sections found in chromosomes is explained by Graeme Finlay in his book, "Human Evolution: Genes, Genealogies, and Phylogenies". These other telomere repeats are due to repair patches that have occurred in the past. His book is actually the finest presentation of DNA evidence for human evolution that I have ever found. Highly recommended, although his discussion of HC2 fusion is very brief compared to the other DNA presentations. This is from his section on "Old scars on DNA", and how these scars are randomly generated but shared across humans and the other great apes, indicating shared ancestry. The objection fails when understood.
"Some 50 short, well-conserved interstitial telomeric repeats, (TTAGGG)n, are present in the human genome. Sequencing studies indicated that they arose as distinct insertion events, probably generated by the action of the enzyme telomerase, which has the function of adding TTAGGG units at the authentic telomeres. These inserts have the characteristics of emergency DNA repair patches that were recruited to hold double stranded breaks together." (p. 146-147).
Numerous DNA patches and repairs that are randomly produced and randomly repaired are exactly shared between humans and the other great apes. Some of these patches contain telomeres so the anti-evolutionist objections are disproven. To understand how DNA repair patches point to near proof of human evolution as explained by Finlay, see the short blog on evolution and DNA patches. Instead of being a problem for evolution, interstitial telomeres actually support evolution because they nest in evolutionary phylogenetic trees confirming evolution. As usual, a close examination of anti-evolutionist objections reveals motivated reasoning and lazy "research"; pushing out "possibilities" without testing them and not knowing the literature well.
4. Chromosomal fusions and splits occurred in our distant past. As early as the 1980s scientists were able to piece that history together. During meiosis crossing over occurs and also chromosome sections can break out and be inserted in the opposition direction (inversion = Inv). In comparing our chromosomes to other great apes, insertions, deletions and inversions were noted and these events can be seen as part of our genetic history. They nest in a hierarchal pattern confirming common descent in the great apes. Roman numerals refer to chromosome numbers.
5. A comment regarding a person making claims that HC2 can't be a fusion. Comments from a geneticist on Reddit and the creationist Tomkins.
6. Actually there was some shuffling of both ends of the chromosomes before the fusion took place. A study published in August of 2022 appears to have narrowed the fusion time between 800,000 and 1 mya before modern humans, Neanderthals and Denisovans split off. In addition, another study showed there probably was a bottleneck in our ancestors about that time and so it would have been easier for the fusion to become fixed in a smaller population.
From: Hawks, John. August 31, 2023. When did Human Chromosome 2 Fuse? Full explanation and discussion in: https://johnhawks.net/weblog/when-did-human-chromosome-2-fuse/?fbclid=IwAR0ScYtuG_g7a8ZcGkDWKQOdkrT4enoI4VnWBlPuf7l3SnL2ziSPgFaqEhM The fusion represents what is called a Roberstonian translocation. This fusion is not rare; it occurs in 1:1000 people so if you are in a city of 2 million there are about 2,000 people walking around with 45 chromosomes and are perfectly healthy and probably some may be ignorant that their chromosome number is unusual. They have the same basic DNA we have but one less chromosomal luggage piece. After the fusion event, other mutations occurred to our chromosome 2 including in the fusion site, and duplications of chromosome 9 moved into 2. When compared to the orangutan genome, HC2 carries two inversions. The first shows after a break after orangutans and the second differentiates chimps from gorillas. This all is explained elegantly by evolution but not by common design. There is no reason these inversions happened as they did showing common descent; they do not fit into common design as an explanation. See below:
Summary - Incredibly, antievolutionists are still trying to claim humans never evolved and that the fusion never took place. All the potential objections put forward to discount that our chromosome 2 is a fusion that I know of have been answered. There are no rational reasons why HC2 is not a fusion. This actually is instructive as to the agendas and motivations of anti-evolutionists, which is an important observation to take away from PhD anti-evolutionists that raced to attack HC2 fusion without doing their homework.
Lastly, some of you may be wondering how going from 48 to 46 chromosomes could have happened. It actually can occur in just two generations with inbreeding and later would spread throughout the population. A Punnett square at the end of this article shows how it probably happened.
Conclusion
Why then did I choose shared ERVs and not HC2 fusion as one of my two best examples for evolution? Because I suppose a creationist could still claim that God created chimps and the other great apes with 48 chromosomes, and then fused two chromosomes together when creating humans. That’s possible I guess, but HC2 fusion is still best explained by evolution and not common design. How it was determined shows that evolution is science. With shared ERVs, there is no getting around that these old parasitic viral tags rise to the level of proof of evolution and common ancestry in humans (see shared ERVs, this site). Indeed, in my opinion all creationist attempts to date have failed to discount shared ERVs and human evolution. Even William Lane Craig published a book in 2021 supporting human evolution but also an attempt to save a historical Adam. Another book by Joshua Swamidass proposes a historical Adam while admitting human evolution based on genetics. I posit that their attempts to keep a historical Adam and Eve just reveals apologist desperation but at least they are moving creationism towards accepting human evolution. See also the discussion of pseudogenes here and how they also support evolution.
Human chromosome fusions are not rare. For example it's not rare for Robertsonian Translocations to occur where two chromosomes accidentally fuse during meiosis that have the centromeres near the tips (acrocentric chromosomes), so little DNA is damaged. The person is usually phenotypically normal but since they have 45 instead of 46 chromosomes they may not know this until they try and have children. This occurs in 1:1,000 people so in a city of 2 million for example, there are 2,000 people walking around looking normal but with 45 chromosomes instead of 46. There is even a case of three children that are normal with 44 chromosomes because two people who had 45 chromosomes from Robertsonian translocations mated.
Human Chromosome 2 is a fusion of an ancestor that appears similar to current chimps' chromosomes 12 + 13, now called 2A and 2B (our closest living cousin). We did not evolve from modern chimps but we shared a common ancestor about 6- 7 million years ago with them. The fusion happened after we split from our chimp/bonobo ancestor. It is consistent with human evolution and our shared ancestry with our great ape cousins. It represents human evolution and an example of "macroevolution". Continued denial by many anti-evolutionists demonstrates desperation to hold onto a view which is not based in reality, science nor history, and further reveals a commitment to resistance based on preexisting anti-evolution ideology or religious beliefs only.
References
There's Proof of Evolution Hiding in Your DNA
Human Evolution: Genes, Genealogies and Phylogenies. 2013. Finlay, Graeme. 2021 Paperback ed. University Printing House, Cambridge, CB2 8BS, UK. 359pp.
Addendum: going from 48 to 46 chromosomes in a pre-human population with just two generations. It would then need to be fixed. Eggs are represented on the vertical axis and sperm on the horizontal axis.
Diagram by the author.
