The debate regarding common ancestry between humans and primates is often disputed from two different perspectives – Creationists versus Evolutionists. In addition to examining the distinct phenotypic similarities between the two species, researchers have utilized the latest genomic tools to analyze the DNA sequences in hopes of finding answers. If humans have 23 pairs of chromosomes and chimpanzees have 24 pairs, how could we possibly be of common descent? The answer is simple – over time, the telomeres of two chromosomes in the common ancestor (2A and 2B in the chimpanzee) fused together to form a single chromosome (chromosome 2 in human).
Dr. Jeffrey Tomkins is a Research Associate at the Institute for Creation Research and received his Ph.D. in genetics from Clemson University. He has written many publications disputing claims regarding the origin of human chromosome 2 and the end-to-end telomere fusion of the chimp chromosomes 2A and 2B. His publications claim that human chromosome 2 was not a result of the fusion of 2 ancestral chromosomes. Dr. Tomkins’ religious presuppositions and ideals supporting Creationism lead him to deny the Evolutionary perspective of this genomic dispute.
Claims against fusion
Centromere: Researchers search for a cryptic centromere, remnant of the fused chromosomes, by searching for alphoid DNA sequences in human chromosome 2. The issue with this is that the 171 base-pair alphoid sequence is not unique to centromeres (Tompkins 2013).
Tomkins states that there is a lack of correspondence surrounding the fusion region between the chimpanzee chromosomes and chromosome 2. He claims that there was a large loss of chimp DNA in the hypothetical fusion, and many genes have no homology corresponding to chimpanzee chromosome 2A or 2B (Tomkins 2013a).
Degenerative telomeric regions: Tomkins claims that the telomeric fusion region is highly degenerative. He cites a publication by Fan et al. stating that “Only 48% of the 127 repeats in RP11–395L14 and 46% of the 158 repeats in M73018 are perfect TTAGGG or TTGGGG units” (Tomkins 2013b). His conclusions on this finding question how these telomeric regions could be so degenerate.
Chromosome fusions representing telomere-telomere signatures are not presently documented, except for the hypothetical fusion of human chromosome 2. This absence of documented end-to-end telomere fusions in living mammals is largely due to the fact that telomeres contain a highly specialized end cap called the shelterin protein complex that protects them from fusion (Tomkins and Bergman 2011b).
Analyses by Tomkins claim that the fusion site on chromosome 2 is located inside a gene called DDX11L2. This gene is encoded on the reverse strand and encodes a key regulatory switch. Due to the functional nature of the gene located on the fusion site, Tomkins argues that the gene did not arise by the fusion of two telomeres, but rather is an important gene that exists for its functionality (Tomkins 2013).
Addressing Counter-claims to fusion:
Centromere: While the alphoid sequence is not unique to centromeres, it is associated with with them; the fact the alphoid sequences are found at the predicted location of the cryptic centromere, which can be approximated by comparing the bands of human chromosome 2 with the bands of both chimpanzee chromosomes 2a and 2b, provides strong circumstantial evidence in favor of 2q21 containing the remains of a degraded centromere.
DDX11L2: The existence of the functional gene, DDX11L2, within the alleged fusion site is often referenced as evidence against fusion; however, it’s likely that this gene serves as evidence for fusion. The entire DDX11L family of genes was found to exist exclusively in sub-telomeric regions, regions very close to the telomeres of chromosomes. Because the repetitive DNA sequence found in telomeric and sub-telomeric regions make the translocation of genes very easy relative to other regions of the chromosome, it is very likely that a copy of the DDX11L gene family, DDX11L2, translocated to the telomeric sequences found at 2q13(Costa et al 2009).
Degenerative Telomeric Regions: Tomkins points out that the telomeric repeat arrays within the fusion region were degenerative and “unexpectedly small in size” (Tomkins, 2013b). The shelterin complex formed by six telomere-specific proteins associated with the repeating arrays of TTAGGG sequences is associated with the protection of telomeres from events such as fusion. The shortening of telomeres without the protective activity of shelterin results in genomic instability (O’Sullivan et al, 2010). Given this information, one would expect the genome sequence of this fusion site to lack the repeating arrays of telomeric regions, just as researchers have found. If the telomeres of the original chromosomes had not been shortened and susceptible to genomic instability, the shelterin complex would have acted as a “safe-guard” to protect the ends of the chromosomes from end-to-end telomere fusion. Therefore, Tomkins’ assumption that the size of the telomeric region at the fusion site was “unexpectedly small” is a faulty assumption.
Supporting Evidence for Fusion of Chromosome 2
In addition to the evidence refuting Tomkins’ claims against the fusion of two chromosomes in an ancestor common to chimpanzee, researchers have further examined the telomeric regions, centromeric regions, and actual DNA sequences of chromosome 2 in humans. The fusion events are widely accepted among the genomic and bioinformatic communities.
The repeating nucleotide sequence found in human telomeres, [TTAAGGG]n, is conserved in chimps (Luke and Verma, 1993). Within the human chromosome 2 a likely candidate locus for fusion was found near 2q13. Two allelic genomic cosmids, c8.1 and c29b, were both found to contain arrays of the vertebrate telomeric repeat in an adjacent arrangement 5′(TTAGGG)n- (CCCTTAA)n3′. Through experimentation, this locus, containing inverted repeats can be speculated to be the remains of a telomere to telomere fusion, which provides strong evidence that the fusion site of the chimpanzee chromosomes, 2a and 2b, on the human chromosome 2 lies at 2q13 (Ijdo et al, 1991). This lends further support to the speculated fusion event.
During the formation of human chromosome 2, one of the centromeres corresponding to chimp chromosome 13 because inactivated. This centromere is located on the human chromosome in position 2q21 (Hillier et al, 2005) . The centromeric structure deteriorated following these events. This area consists of 7,800,000 bp with location chr2:130,000,001-137,800,000 (UCSC Genome Browser).
References
Tomkins, Jeffrey P. Ph.D. “New Research Debunks Human Chromosome Fusion.” Acts & Facts. 42 (12) (2013a).
Tomkins, Jeffrey P. Ph.D. “Alleged Human Chromosome 2 “Fusion Site” Encodes an Active DNA Binding Domain Inside a Complex and Highly Expressed Gene—Negating Fusion.” Answers in Genesis. (2013b).
O’Sullivan, Roderick J. and Karlseder, Jan. “Telomeres: protecting chromosomes against genome instability.” Nat Rev Mol Cell Biol. 2010 Mar; 11(3): 171–181.
Hillier, LaDeana W. “Generation and annotation of the DNA sequences of human chromosomes 2 and 4.” Nature 434, 724-731 (7 April 2005) | doi:10.1038/nature03466.
Fan, Yuxin, Elena Linardopoulou, Cynthia Friedman, Eleanor Williams, and Barbara J. Trask. “Genomic Structure and Evolution of the Ancestral Chromosome Fusion Site in 2q13–2q14.1 and Paralogous Regions on Other Human Chromosomes.” Genome Research 2002 Nov; 12(11): 1651–1662. doi: 10.1101/gr.337602
Luke, Sunny, and Ram S. Verma. “Telomeric repeat [TTAGGG]n sequences of human chromosomes are conserved in chimpanzee (Pan troglodytes).” Molecular and General Genetics March 1993, Volume 237, Issue 3, pp 460-462.
Idjo, J. W., A. Baldini, D. C. Ward, S. T. Reeders, and R. A. Wells. “Origin of human chromosome 2: An ancestral telomere-telomere fusion.” Proceedings of the National Academy of Sciences USA Vol. 88, pp. 9051-9055, October 1991 Genetics
Avarello, R., A. Pedicini, A. Caiulo, O. Zuffardi, and M. Fraccaro. “Evidence for an Ancestral Alphoid Domain on the Long Arm of Human Chromosome 2.” Human Genetics 89, no. 2 (May 1992): 247–49.
UCSC Genome Browser: Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. The human genome browser at UCSC. Genome Res. 2002 Jun;12(6):996-1006.
The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature. 2005 Sep 1;437(7055):69-87. PMID: 16136131
Costa, Valerio, Amelia Casamassimi, Roberta Roberto, Fernando ,Gianfrancesco, Maria R Matarazzo, Michele D’Urso,Maurizio D’Esposito, Mariano Rocchi and Alfredo Ciccodicola. “BMC Genomics.” DDX11L: A Novel Transcript Family Emerging from Human Subtelomeric Regions. BMC Genomics, 28 May 2009. Web. 15 Feb. 2016. <http://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-10-250>.
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