Human Chromosome 2 is a fusion of two ancestral chromosomes

Alec MacAndrew

Introduction

All great apes apart from man have 24 pairs of chromosomes. There is therefore a hypothesis that the common ancestor of all great apes had 24 pairs of chromosomes and that the fusion of two of the ancestor's chromosomes created chromosome 2 in humans. The evidence for this hypothesis is very strong.

The Evidence

Evidence for fusing of two ancestral chromosomes to create human chromosome 2 and where there has been no fusion in other Great Apes is:



1) The analogous chromosomes (2p and 2q) in the non-human great apes can be shown, when laid end to end, to create an identical banding structure to the human chromosome 2. (1)

2) The remains of the sequence that the chromosome has on its ends (the telomere) is found in the middle of human chromosome 2 where the ancestral chromosomes fused. (2)

3) the detail of this region (pre-telomeric sequence, telomeric sequence, reversed telomeric sequence, pre-telomeric sequence) is exactly what we would expect from a fusion. (3)

4) this telomeric region is exactly where one would expect to find it if a fusion had occurred in the middle of human chromosome 2.

5) the centromere of human chromosome 2 lines up with the chimp chromosome 2p chromosomal centromere.

6) At the place where we would expect it on the human chromosome we find the remnants of the chimp 2q centromere (4).



Not only is this strong evidence for a fusion event, but it is also strong evidence for common ancestry; in fact, it is hard to explain by any other mechanism.

Explanations

Telomere evidence

The telomere is a sequence of DNA at the end of the chromosome. The function of the telomere is to protect the ends of the chromosomal DNA strands during replication. The ends of the strands are very vulnerable to mutations or deletions. Telomeres consist of, or contain long stretches of simple DNA sequences that are repeated many times. The telomeres tend to be shortened over time and are restored by an enzyme called telomerase which lengthens the sequence. If the telomere becomes too short in somatic cells, errors in duplication can occur leading to cancers.



The telomere sequence is highly conserved in different groups of organisms. For example vertebrates have the sequence TTAGGG repeated many times. (In primates the sequence is repeated 500 to 3500 times). Adjacent to the telomere, are regions with other DNA repeats (known as Telomere Associated Repeats) but these regions, rather than being highly conserved, are highly polymorphic - that is they have many variations even within the same species. Nevertheless the pretelomeric region can be easily recognised in closely related species. Occasionally genes are found in the pretelomeric region.



Now these telomeric and pretelomeric sequences are normally found only on chromosome ends. However, in human chromosome 2, there is strong evidence for chromosome fusing in that there is a pretelomeric sequence, a telomeric sequence, an inverted telomeric sequence and an inverted pretelomeric sequence in that order in the middle of the chromosome.

Centromere evidence

Turning now to the centromere. The process of somatic cell division (mitosis) is as follows (this is a very brief and simplified summary to explain the centromere):

1) The genetic material is duplicated. At this stage, called interphase, the DNA strands are extended and invisible. Although there are still 23 pairs of chromosomes in humans, each one has twice the DNA material compared with a non-dividing cell



2) The chromosomes condense: ie they become shorter and fatter (they actually become coiled coiled coils around a core protein called a histone) and visible in a microscope. All the pictures we see of chromosomes are when they are condensed during duplication. The genetic material has been duplicated and each chromosome consists of two sets of genetic material connected at the centromere. Each set of genetic material is known as a chromatid. Since the centromere is generally somewhere away from the ends, the chromosome has the form of an X-shape with the two arms (the sister chromatids) joined at the centromere. The mitotic spindle ( a structure crossing from one side of the cell to the other) forms. The nuclear envelope breaks down. This is prophase.



3) The chromosomes become aligned so their centromeres are on the centre of the spindle. At each centromere there are plate structures (called kinetochores) for attachment of microtubules to the centromere. This is metaphase



4) The sister chromatids separate forming a pair of identical chromosomes and are drawn to opposite ends of the cell to the spindle poles. This is anaphase.



5) A new cell wall in the middle of the original cell forms, a nuclear membrane forms around the chromosomes and the chromosomes disperse and become invisible. We now have two cells. This is known as telophase.



The centromere can be seen on a condensed chromosome as a pinched region. It has proteins from outside inwards which form kinetochores, which form the central portion (histones) and which attach the sister chromatids one to the other.



Let us re-iterate what we find on human chromosome 2. Its centromere is at the same place as the chimpanzee chromosome 2p as determined by sequence similarity. Even more telling is the fact that on the 2q arm of the human chromosome 2 is the unmistakable remains of the original chromosome centromere of the common ancestor of human and chimp 2q chromosome, at the same position as the chimp 2q centromere (this structure in humans no longer acts as a centromere for chromosome 2.

Conclusion

The evidence that human chromosome 2 is a fusion of two of the common ancestor's chromosomes is overwhelming.



1. http://www.fhcrc.org/labs/trask/subtelomeres/

2. Yunis, J. J., Sawyer, J.R., Dunham, K., The striking resemblance of high-resolution g-banded chromosomes of man and chimpanzee. Science, Vol. 208, 6 June 1980, pp. 1145 - 1148

3. IJdo JW, Baldini A, Ward DC, Reeders ST, Wells RA, Origin of human chromosome 2: an ancestral telomere-telomere fusion. Proc Natl Acad Sci U S A 1991 Oct 15;88(20):9051-5; available on-line here:

http://www.pnas.org/cgi/reprint/88/20/9051.pdf