Human‐specific Changes of Genome Structure

R Alan Harris, Baylor College of Medicine, Houston, Texas, USA
Aleksandar Milosavljevic, Baylor College of Medicine, Houston, Texas, USA

Published online: April 2008

DOI: 10.1002/9780470015902.a0020997

Abstract

Genomic changes occur along a size continuum ranging from small‐scale base substitutions to large‐scale cytogenetically detectable chromosome rearrangements. Intermediate‐scale changes between these two extremes are the least studied group of genomic changes. The genomic triangulation method was developed to detect intermediate‐scale changes by integrating genomic sequence and mapping data from human, chimpanzee and rhesus macaque. Human‐specific genomic changes associate with segmental duplications (SDs), involve numerous genes and may result in human‐specific phenotypic traits.

Keywords: comparative genomics; genome structure; primate evolution; segmental duplications; genomic disorders

Figure 1.

Detection by genomic triangulation of a human‐specific breakpoint induced by an insertion. In this example, blockset construction reveals a chimp–rhesus conserved block with human–chimp and human–rhesus blocks aligning except for a gap suggesting a human‐specific insertion. Gapsets are represented as gap maps in which circles represent gaps and circle coordinates indicate gap sizes in specific genomes. Gapsets on the left indicate breakpoints in human–chimp and human–rhesus pairwise comparisons. Ancestral gapsets on the right indicate the breakpoint between human and the ancestor. Reproduced with permission from Harris et al..

Figure 2.

Breakpoints in the human, chimpanzee and rhesus lineages relative to the human–chimpanzee and human–rhesus ancestor. Chromosomes are represented by a left and right pane. Horizontal lines in the left pane represent intermediate‐scale breakpoints (10 kbp–4 Mbp) detected by genomic triangulation. Horizontal lines in the right pane represent breakpoints involved in large‐scale changes (>4 Mbp). Numbers above each pane show the total breakpoints within the pane. Reproduced with permission from Gibbs et al..

Figure 3.

Human‐specific breakpoints. (a) Chromosome ideograms of 130 human‐specific breakpoints detected by genomic triangulation, with breakpoint counts by chromosome. (b) Gap map with ancestor gap lengths on the x‐axis and human gap lengths on the y‐axis. Only gaps greater than 10 kb in at least one of the genomes and smaller than 4 Mb were considered. Some insertions occur to the right of the y=x axis because visual inspection revealed inaccuracies in gap sizing, providing evidence for human insertion. (c) Size distribution of detected human‐specific insertions. The percent identity of SDs can indicate the approximate age of duplication events. Reproduced with permission from Harris et al..

close

References

Bailey JA and Eichler EE (2006) Primate segmental duplications: crucibles of evolution, diversity and disease. Nature Reviews. Genetics 7: 552–564.

Blanchette M, Kent WJ, Riemer C et al. (2004) Aligning multiple genomic sequences with the threaded blockset aligner. Genome Research 14: 708–715.

Cardona‐Maya W, Lopez‐Herrera A, Velilla‐Hernandez P, Rugeles MT and Cadavid AP (2006) The role of mannose receptor on HIV‐1 entry into human spermatozoa. American Journal of Reproductive Immunology 55: 241–245.

Cheng Z, Ventura M, She X et al. (2005) A genome‐wide comparison of recent chimpanzee and human segmental duplications. Nature 437: 88–93.

Consortium The Chimpanzee Sequencing and Analysis (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Science 437: 69–87.

Demuth JP, Bie TD, Stajich JE, Cristianini N and Hahn MW (2006) The evolution of mammalian gene families. PLoS ONE 1: e85.

Dumas L, Kim YH, Karimpour‐Fard A et al. (2007) Gene copy number variation spanning 60 million years of human and primate evolution. Genome Research 17: 1266–1277.

Gibbs RA, Rogers J, Katze MG et al. (2007) Evolutionary and biomedical insights from the rhesus macaque genome. Science 316: 222–234.

Gonzalez E, Kulkarni H, Bolivar H et al. (2005) The influence of CCL3L1 gene‐containing segmental duplications on HIV‐1/AIDS susceptibility. Science 307: 1434–1440.

Harris RA, Rogers J and Milosavljevic A (2007) Human‐specific changes of genome structure detected by genomic triangulation. Science 316: 235–237.

Kang PB, Azad AK, Torrelles JB et al. (2005) The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan‐mediated phagosome biogenesis. Journal of Experimental Medicine 202: 987–999.

Newman TL, Tuzun E, Morrison VA et al. (2005) A genome‐wide survey of structural variation between human and chimpanzee. Genome Research 15: 1344–1356.

Redon R, Ishikawa S, Fitch KR et al. (2006) Global variation in copy number in the human genome. Nature 444: 444–454.

Stankiewicz P and Lupski JR (2002) Genome architecture, rearrangements and genomic disorders. Trends in Genetics 18: 74–82.

Further Reading

Blanchette M, Green ED, Miller W and Haussler D (2004) Reconstructing large regions of an ancestral mammalian genome in silico. Genome Research 14: 2412–2423.

Bourque G, Pevzner PA and Tesler G (2003) Reconstructing the genomic architecture of ancestral mammals: lessons from human, mouse, and rat genomes. Genome Research 14: 507–516.

Bourque G, Tesler G and Pevzner PA (2006) The convergence of cytogenetics and rearrangement‐based models for ancestral genome reconstruction. Genome Research 16: 311–313.

Froenicke L, Caldes MG, Graphodatsky A et al. (2006) Are molecular cytogenetics and bioinformatics suggesting diverging models of ancestral mammalian genomes? Genome Research 16: 306–310.

Kimura M (1968) Evolutionary rate at the molecular level. Nature 217: 624–626.

Ma J, Zhang L, Suh BB et al. (2006) Reconstructing contiguous regions of an ancestral genome. Genome Research 16: 1557–1565.

Ohno S, Wolf U and Atkin NB (1968) Evolution from fish to mammals by gene duplication. Hereditas 59: 169–187.

Rocchi M, Archidiacono N and Stanyon R (2006) Ancestral genomes reconstruction: an integrated, multi‐disciplinary approach is needed. Genome Research 16: 1441–1444.

Wienberg J (2005) Fluorescence in situ hybridization to chromosomes as a tool to understand human and primate genome evolution. Cytogenetic Genome Research 108: 139–160.

Web Links

Interactively explore the data input into genomic triangulation and the detected lineage specific breakpoints through the Genboree browser – http://www.genboree.org/java‐bin/GenomicTriangulation/index.jsp?isPublic=Yes.

The Centre for Applied Genomics (TCAG) Database of Genomic Variants – http://projects.tcag.ca/variation/

Related Sub-Topics:

Evolution of Coding and Functional Modules | Human Evolution | Evolutionary Genomics
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Human‐specific Changes of Genome Structure
 
How to Cite close
Harris, R Alan, and Milosavljevic, Aleksandar(Apr 2008) Human‐specific Changes of Genome Structure. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020997]