Chromosome 2 fusion?

Question

I read this article by Jeffrey Tomkins and Jerry Bergman claiming to debunk chromosome 2 fusion. Is there anything wrong with these conclusions?

" 1.The reputed fusion site is located in a peri-centric region with suppressed recombination and should exhibit a reasonable degree of tandem telomere motif conservation. Instead, the region is highly degenerate—a notable feature reported by a previous investigation.

1. In a 30 kb region surrounding the fusion site, there exists a paucity of intact telomere motifs (forward and reverse) and very few of them are in tandem or in frame.

2. Telomere motifs, both forward and reverse (TTAGGG and CCTAAA), populate both sides of the purported fusion site. Forward motifs should only be found on the left side of the fusion site and reverse motifs on the right side

3. The 798-base core fusion-site sequence is not unique to the purported fusion site, but found throughout the genome with 80% or greater identity internally on nearly every chromosome; indicating that it is some type of ubiquitous higher-order repeat.

4. No evidence of synteny with chimp for the purported fusion site was found. The 798-base core fusion-site sequence does not align to its predicted orthologous telomeric regions in the chimp genome on chromsomes 2A and 2B.

5. Queries against the chimp genome with the human alphoid sequences found at the purported cryptic centromere site on human 2qfus produced no homologous hits using two different algorithms (BLAT and BLASTN).

6. Alphoid sequences at the putative cryptic centromere site are diverse, form three separate sub-groups in alignment analyses, and do not cluster with known functional human centromeric alphoid elements."

I've also heard them say that there has to be a fusion in every living thing that evolved or evolution isn't true. Is that true or not?

The article is here

• Part one
• Part two

Answer 1

Regarding the Papers referenced above:

If the authors maintain that the evidence at the site of fusion is not clear and that explanations as to how this happened are flawed that is possibly concedable. They would need to do more homework than these papers. The discussion of vestigial centromere sequences and telomere motifs being inverted is interesting, though contrary views have been written up elsewhere. I'm not going to review that evidence as I think its not primary to the question at hand...

I would point out that the centromere and telomere sequences are highly repetitive - they are so repetitive that they are often associated with unreliable sequencing in a typical genome build. While its possible some will be found in future builds of the human genome, such sequences are just as likely to have been excised during mitosis or by mutation. There would be strong selection pressure for them to be excised quickly; having two centromeres on one chromosome would probably be a fatal trait and the same is probably true for telomerase susceptible sequences in the middle of a chromosomal arm is too. A lot has happened at the point of fusion and 150 kB of DNA seems to have included itself which is not from the original Chr 2A or 2B.

I think there is some confusion here: The fusion models examined do not predict the fusion from the local configuration of bases. The main evidence for fusion has always been the fact that the two pieces of human chromosome 2 are nearly identical to chromosomes 2A and 2B of apes - typically 96-98% identical. The genes are almost entirely in the same order, the inter-genic regions are very similar All along the 2A/2B length - millions of bases. The site of fusion ad models for its occurrence is merely confirming what we already - there are two chromosomes somehow stuck together. Since both papers focus on the site of combination and do not adequately address this primary piece of information, they seem to be missing this point.

The chances are infinitesimal that human chr 2 were to resemble those of other primates at random. This is what you say in science when you mean 'impossible'. One simply doesn't see a segment of DNA the size of Chr 2A and 2B being so similar for such a length when we look at rats, dogs, worms or any more distantly related living thing. But for every primate the relationship corresponds to humans the same way. In addition studies show that these highly similar blocks of DNA sit right next to the site of fusion and show a crossover where the fusion probably occurred. Some recent hominids - Neanderthals and Denisovans had the chr 2 fusion as well.

I have to say is that there's always a chance that chromosome 2 fusion did not happen though in my view there's a tremendous amount of evidence that it did. The second most likely explanation is that all the other apes had their chromosome 2 break into 2 pieces at some susceptible site.

I don't quite agree that chromosome 2 fusion is an indispensable or even leading piece of evidence that means that humans and the other primates are interrelated. That question is a different kettle of fish and the relationship between Human chromosome 2 and the chromosomes of other primates is just one contributing point. All the other chromosome sequences in primates are the same, and nearly every gene in human beings is closer to primates than to other animals. If they had not found chromosome 2 fusion in the genome sequences few if anybody would have worried about it.

As to your last question - I don't know if its necessary that chromosomal fusion must occur in every living thing, but it appears that it has. In fact what we see as we look at all the diverse chromosomes being sequenced, is that most chromosomes have been merged or rearranged over and over again. Over long periods of evolutionary time, a typical chromosome looks like a patchwork quilt stitched up from pieces of other chromosomes. These relationships are called synteny, which reaffirm the thesis that all living things came from a single point of origin, if you go back far enough. Really, the fusion point of Chr2 is interesting because its a relatively new event; by picking through the pieces we might find some understanding of something that appears to be a common phenomenon in genome dynamics.

The above image comes from a review of methods to identify syntenic regions. It identifies regions of human chromosome 7 and similar regions of mouse chromosomes, identifying regions on mouse chromosomes 6, 9, 11, and 12 with substantial similarities as well as a little bit of chr 2. Hu chr 7 is 158 million bases long, so even a small band (> 1/1000th of the full length) on this chart means 100,000s of bases.

If all these syntenic relationships are considered together they can construct chromosomal rearrangement events that compare with the phylogenetic tree and typically verify speciation events that separate the two organisms being compared.

Whoops - just found this. Take a look at this Biology.SE question: it refers to Robertsonian translocation where the long arms of several of the chromosomes chr 14, 15, 16, 21 and 22 are known to sometimes fuse, resulting in viability. The answer there is useful - these variants don't tend to produce offspring, but it only takes one time. Its only happened once in the past 5 million years or so. So another point of view there.

That should't discourage the authors from trying again.

All this being said, as a scientific question I'd rather have a discussion like this, based on evidence and facts that anyone can evaluate. The authors did quite a bit of homework and read some of the literature that is out there. This is the right direction some of the creationists are taking here and I personally hope that they keep at it.

If science is to have any merit (or fun) at all, its because any idea can be called into question and be re-evaluated at any time by anyone.

Answer 2

This reply needs to contain a number of links to qualify each of my claims. Unfortunately this site won't allow me to include more than two links because I am a new user. Please see this post which contains the same response and all the necessary links as well.

I would be very careful trusting any claims published by the young earther Jeffrey Tomkins. In my experience, each of his claims needs to be thoroughly researched because I have found him to be less than rigorous (sloppy) in at least one other paper he has published. He has faced similar accusations from others in the past.

I'm not saying dismiss everything he says: I'm saying take all of his claims with a grain of salt, expect there to be exaggerations, errors and misleading claims (he has a young earth creationist agenda)

If you are ever concerned about anything he writes, you will need to look at the evidence for yourself. I will attempt to answer your questions here.

In a 30 kb region surrounding the fusion site, there exists a paucity of intact telomere motifs (forward and reverse) and very few of them are in tandem or in frame.

This is true, but it isn't surprising (at least not to me). To quote popular science blogger, Carl Zimmer:

The ends of chromosomes are very vulnerable places. If they simply dangle loosely, DNA-cutting enzymes can nibble away at them, destroying the genes they encounter. The dangling end of one chromosome can also get attached to the dangling end of another, fusing chromosomes together. We are mostly protected from such changes thanks to special proteins called telomerases. They tack on little repeating bits of DNA, which form a loop–a telomere–so that chromosomes end as a hairpin curve, rather than dangling ends.

It is this loop that prevents chromosomes from undergoing the type of fusion that we see in the second chromosome. Now telomeres naturally shorten and become mutated with age. If we encountered two fused chromosomes (with the telomeres joined end to end) we should expect that this could only happen where the telomeres are short enough and mutated enough to allow this to happen. Only when they can no longer form that protective loop, can they become fused.

Experiments like this have shown that defective telomeres with few repeats are vulnerable to chromosome fusion.

Here is what the fusion site actually looks like - the highlighted repeating elements (TTAGGG and CCCTAA) are those that are still perfectly formed. If I relax my criteria a little and also highlight those repeating elements that have just one single mutation, this is what the fusion site looks like. To raise doubts that what we are looking at here are a series of repeats of "TTAGGG" joined to a series of repeats of "CCCTAA" is either asinine or dishonest.

Telomere motifs, both forward and reverse (TTAGGG and CCTAAA), populate both sides of the purported fusion site. Forward motifs should only be found on the left side of the fusion site and reverse motifs on the right side

(Note: it is CCCTAA not CCTAAA)

This is just pure nonsense, I am tempted even to call it a lie but I can't be sure. I have looked into this claim by searching through the 20,000 bases that surround the fusion site. In those 20,000 bases there is exactly 1 instance of TTAGGG that occurs before the fusion site and 1 instance of CCCTAA that occurs before the fusion site (No more than we should expect to occur by chance alone in any sequence this long).

After the fusion site (and away from it), there is 1 more instance of CCCTAA and 3 more instances of TTAGGG (No more than we should expect to occur by chance alone in any sequence this long).

Don't take my word for it. Here are 20,023 bases that surround the fusion site.

The 798-base core fusion-site sequence is not unique to the purported fusion site, but found throughout the genome with 80% or greater identity internally on nearly every chromosome; indicating that it is some type of ubiquitous higher-order repeat.

This sounds like more rubbish (even a lie perhaps). Using BLAT to search for the actual sequence, there is no location in the human genome except for this place on chromosome 2 where we see a sequence of repeating TTAGGG joined to a sequence of repeating CCCTAA. If the authors claim to have found another site like this, why have they not linked to it?

We could also use BLAT to search for an idealised sequence of perfect repeats. Once again, the only hit that includes both the TTAGGG and the CCCTAA is in this exact location on chromosome 2.

We do unsurprisingly find sequences of repeating TTAGGG but what makes this fusion site unique is that those repeats are followed by repeating CCCTAA - that isn't found anywhere else in our genome of over 3 billion base pairs.

Think about that for a moment. A sequence with a signature as unique as this, found in the exact place where scientists expect to find it!

No evidence of synteny with chimp for the purported fusion site was found. The 798-base core fusion-site sequence does not align to its predicted orthologous telomeric regions in the chimp genome on chromsomes 2A and 2B.

First of all, this claim doesn't even make sense. The 798 bases he talks about are just the telomeric repeats. If they are telomeric repeats then they will be found on the telomeres of chromosomes 2A and 2B. Perhaps he made a mistake here and was talking about the wider region surrounding this fusion site?

It is true that there is a lack of synteny in the wider region surrounding this.

This became well understood with the sequencing of the gorilla genome. There was a paper published explaining how this happened in 2012. If you prefer, here is the layman's explanation with diagrams.

Queries against the chimp genome with the human alphoid sequences found at the purported cryptic centromere site on human 2qfus produced no homologous hits using two different algorithms (BLAT and BLASTN).

This isn't true either. Where does he get this nonsense from? I have downloaded the alphoid sequences from the defunct centromere on human chromosome 2 and used BLAT (against Chimpanzee Feb 2011) to find their homologs in the chimpanzee. Unsurprisingly they are exactly where we expect to find them on chimpanzee chromosome 2B - where there is a functional centromere.

Think about that for a moment. The very same sequences that form a functioning centromere on chimpanzee chromosome 2B are found exactly where we expect to find them at a defunct centromere on human chromosome 2.

I am busy constructing a detailed write-up on this. I will update this post to provide a link to that.

Alphoid sequences at the putative cryptic centromere site are diverse, form three separate sub-groups in alignment analyses, and do not cluster with known functional human centromeric alphoid elements."

I can't comment on the first claim but it seems irrelevant anyway. I can tell you that these alphoid sequences occur frequently at centromeres all over the human genome from X to 22. More importantly they are appear almost exclusively at centromeres. For example, alphoid 2 appears at centromeres on the following chromosomes: 21, 9 (twice), 11 (twice), 20 (twice), 7 (3x), 22 (5x), 16, 14, 15, 5.

It appears once at an unexpected location on chromosome 9 where there isn't a centromere, but that exact location is rich in other alphoid sequences suggesting that it too is a defunct centromere (or was perhaps duplicated from another centromere).

This will also be covered in that detailed write-up I mentioned.

edit (2 Oct 2015):

I promised to follow up on this post with a detailed write-up on the fossil centromere on chromosome 2. I've done that now (A year and a bit later) - you can find the information I've compiled on the centromere here

Answer 3

If one looks at the sequence map in detail, at the fusion point we find both telomere and pre-telomere sequences. And what is particularly compelling, is that these main groups occur in the correct order. That is, first you see a pre-telomere sequence, then a telomere sequence. Then we see the telomeres inverted and the inverted pre-telomeres after that. This is exactly what would be predicted for a chromosome fusion. Yes, one can quibble (as Tomkins does) that within a particular group that the sequences don't "look exactly as they should". But this would be consistent with ideas proposed here. That these sequences MUST have undergone significant mutation in order for the fusion to even occur! And then of course one would expect mutations to continue after the fusion event as part of normal evolution.