Human Chromosome 2 Fusion

"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:

An Evolutionary Story of Chimps and Us

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 creationist 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. To the creationist, humans and chimps never shared a common ancestor. This is based almost entirely on creationist a priori religious beliefs. 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 the fusion point of 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 Fusion of Our Chromosome 2

This discrepancy in chromosomes between humans and the other great apes theoretically 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

From: Chromosome 2 fusion - a response to a question on biology stack exchange

To further confirm the findings, in 2006 Stefan Muller tagged HC2 with a dye and then applied the same dye tags to an orangutan. 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.

Creationist Objections

Incredibly, creationists are still trying to claim humans never evolved and that the fusion never took place. I would like to introduce you to one of my many heroes exposing the attacks on evolution and science. It was my intent to discuss and invalidate the various creationist objections that have been raised, but she does such a great job, is entertaining, and does so in less than 30 minutes so that it is best to watch her presentation. It is posted below. Here on display is the motivated reasoning, poor scholarship and even lying of some of the most educated creationists in regards to biology. In 40 years of following creationist attacks on evolution, I have discovered that if one drills down far enough and looks up the proper research and good sources, creationist attacks are exposed as misinterpretations, quote mining, and sometimes just plain lying although I also think they are so motivated by their religion and so blinded by confirmation bias that they don’t even realize their ineptitude much of the time. Learn the creationist objections and then do a deep dive into the issues and you will find as I have that creation “science” is not to be trusted and as a bonus the psychology of creationists and why no amount of evidence will probably ever change their fundamental views, will be on display. If you are a creationist or interested in creationism, you must watch this 28 minute video by Erik the Gutsick Gibbon. Really.

Comments from a geneticist on Reddit and the creationist Tomkins.

Secondly, in 2012 a heated exchange occurred on line between the Intelligent Design advocate organization The Discovery Institute and Carl Zimmer. As predicted when the actual facts were presented in detail, the creationists were shown at best to be incompetent and at worst dishonest. The continued denial by creationists that HC2 is not a fusion reveals a complete poverty of their positions and to what extent religious motivation will destroy true reasoning abilities. It’s technical but the bankrupt creationist positions are exposed.

The Mystery of The Missing Chromosome

Another URL: The Mystery of The Missing Chromosome

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. 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.

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 looks like current chimps' chromosomes 12 + 13, now called 2A and 2B. 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 creationists demonstrates desperation to hold onto a view which is not based in reality nor history, and further reveals a commitment to resistance based on religion only.

References

There's Proof of Evolution Hiding in Your DNA

https://www.youtube.com/watch?v=2GfKZlTRNjA

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.