Human‐specific Changes of Genome Structure


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..



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Web Links

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

The Centre for Applied Genomics (TCAG) Database of Genomic Variants –

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Harris, R Alan, and Milosavljevic, Aleksandar(Apr 2008) Human‐specific Changes of Genome Structure. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020997]