Segmental Duplications and Their Role in the Evolution of the Human Genome

Yali Xue, The Wellcome Trust Sanger Institute, Hinxton, UK
Chris Tyler‐Smith, The Wellcome Trust Sanger Institute, Hinxton, UK

Published online: May 2008

DOI: 10.1002/9780470015902.a0020838

Segmental duplications are unusually abundant in the human genome, perhaps because they carry genes whose amplification has been selectively advantageous during primate and human evolution. Their presence leads to genome instability, and so they are associated with genomic disorders, but they are also involved in the continuing evolution of the genome, for example by leading to increases in gene product, variant gene copies and fusion genes.

Keywords: segmental duplication; low copy repeat; copy number variation; genome evolution; human evolution

Figure 1. The human genome has an unusually high segmental duplication content. Estimates of the SD content (Bailey and Eichler, 2006) depend significantly on the data available and method used, and those marked * are preliminary. Nevertheless, the increased SD content in humans is a robust finding.
Figure 2. Location of segmental duplications on human chromosome 1. The number of SDs starting in each 100 kb window (http://eichlerlab.gs.washington.edu/database.html) is shown on the right and an ideogram of the chromosome on the left. Although correspondence between banding pattern and deoxyribonucleic acid (DNA) sequence is only approximate, it can be seen that no large region of the genome is free of SDs, but that they are enriched near the centromere and telomeres.
Figure 3. Duplication and increased expression of the salivary amylase locus AMY1. Chimpanzees have a single copy per haploid genome of the AMY1 gene (bottom left); humans from low-starch populations have an average of 2.7 copies per haploid genome (bottom centre), whereas humans from high-starch populations have an average of 3.4 copies per haploid genome (bottom right). The top part of the figure (in grey) shows inferences about the ancestors. From comparisons with more distantly related species, the chimpanzee–human common ancestor is deduced to have had a single copy (top), with duplication of the locus in early humans (middle) predating the divergence between modern populations. Each box represents a population sample and each pair of lines an individual.
Figure 4. Gene duplication, divergence and polymorphism at the Rhesus locus. Orangutans have a single RH gene (bottom left), while humans have one to three and these are differentiated into RHD and RHCE (bottom right). The top part of the figure (in grey) shows the inferred structures in the ancestors. The orangutan–human common ancestor is deduced to have had a single RH gene, which was duplicated on the lineage leading to African apes and humans (middle). The two genes started to diverge around exon 7 (grey box in RH genes). An additional duplication, the rhesus box (filled arrow) flanks the RHD gene and another gene (SMP1, open arrow) is present in the region.
Figure 5. Formation and expansion of a fusion gene family. The ancestral RGPD gene is inferred to have originated from the fusion of exons 1–20 of the RANBP2 (white arrow) with the last three exons of GCC2 (black arrow; top, in grey). RGPD genes were subsequently duplicated, and clusters are now found on human 2q where the parental genes also lie and also on human 2p (bottom, in black).
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 References
    Avent ND, Madgett TE, Lee ZE et al. (2006) Molecular biology of Rh proteins and relevance to molecular medicine. Expert Reviews in Molecular Medicine 8: 1–20.
    Bailey JA and Eichler EE (2006) Primate segmental duplications: crucibles of evolution, diversity and disease. Nature Reviews Genetics 7: 552–564.
    Cheung J, Estivill X, Khaja R et al. (2003) Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence. Genome Biology 4: R25.
    Ciccarelli FD, von Mering C, Suyama M et al. (2005) Complex genomic rearrangements lead to novel primate gene function. Genome Research 15: 343–351.
    Fortna A, Kim Y, MacLaren E et al. (2004) Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biology 2: 937–954.
    Innan H (2003) A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes. Proceedings of the National Academy of Sciences of the USA 100: 8793–8798.
    Jiang Z, Tang H, Ventura M et al. (2007) Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nature Genetics 39: 1361–1368.
    Perry GH, Dominy NJ, Claw KG et al. (2007) Diet and the evolution of human amylase gene copy number variation. Nature Genetics 39: 1256–1260.
    She X, Jiang Z, Clark RA et al. (2004) Shotgun sequence assembly and recent segmental duplications within the human genome. Nature 431: 927–930.
    Suto Y, Ishikawa Y, Hyodo H et al. (2003) Gene arrangement at the Rhesus blood group locus of chimpanzees detected by fiber-FISH. Cytogenetic and Genome Research 101: 161–165.
 Further Reading
    book Jobling MA, Hurles ME and Tyler-Smith C (2004) Human Evolutionary Genetics. New York: Garland Science.
    book Lupski JR and Stankiewicz P (eds) (2006) Genomic Disorders: The Genomic Basis of Disease. Totowa, NJ: Humana Press.
    book Ohno S (1970) Evolution by Gene Duplication. Berlin: Springer.
    Redon R, Ishikawa S, Fitch KR et al. (2006) Global variation in copy number in the human genome. Nature 444: 444–454.

Related Sub-Topics:

Evolutionary Genomics | Molecular Evolution | Human Evolution
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Article Title: Segmental Duplications and Their Role in the Evolution of the Human Genome
 
How to Cite close
Xue, Yali, and Tyler‐Smith, Chris(May 2008) Segmental Duplications and Their Role in the Evolution of the Human Genome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020838]