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BMC Genomics
2006 May 10;7:271. doi: 10.1186/1471-2164-7-271.
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Comparative genomics of vertebrate Fox cluster loci.
Wotton KR
,
Shimeld SM
.
Abstract
Vertebrate genomes contain numerous duplicate genes, many of which are organised into paralagous regions indicating duplication of linked groups of genes. Comparison of genomic organisation in different lineages can often allow the evolutionary history of such regions to be traced. A classic example of this is the Hox genes, where the presence of a single continuous Hox cluster in amphioxus and four vertebrate clusters has allowed the genomic evolution of this region to be established. Fox transcription factors of the C, F, L1 and Q1 classes are also organised in clusters in both amphioxus and humans. However in contrast to the Hox genes, only two clusters of paralogous Fox genes have so far been identified in the Human genome and the organisation in other vertebrates is unknown. To uncover the evolutionary history of the Fox clusters, we report on the comparative genomics of these loci. We demonstrate two further paralogous regions in the Human genome, and identify orthologous regions in mammalian, chicken, frog and teleost genomes, timing the duplications to before the separation of the actinopterygian and sarcopterygian lineages. An additional Fox class, FoxS, was also found to reside in this duplicated genomic region. Comparison of loci identifies the pattern of gene duplication, loss and cluster break up through multiple lineages, and suggests FoxS1 is a likely remnant of Fox cluster duplication.
Figure 1. Human paralogons of the FOX cluster loci. A schematic representation of paralogy deduced from analysis of the human genome using NCBI map viewer Hs Build 36.1 (Nov 01, 2005) [36]. Gene names are shown above each gene, while numbers in the boxes indicate subfamily. Letters on the far left indicate paralogon designation, while numbers on the far right indicate which chromosome the cluster is found on. Numbers between genes are approximate intergenic distances in Kb. Background shading indicates paralogy.
Figure 2. Genomic organisation of human Fox cluster paralogons and putative orthologous counterparts. Genomic organisation of human (Hs) Fox cluster paralogons and the putative orthologous counterparts we have identified in Mus musculus (Mm), Xenopus tropicalis (Xt), Gallus gallus (Gg), Danio rerio (Dr), Tetraodon nigroviridis (Tn) and Fugu rubripes (Fr). Panels A, B, C and D depict orthologous genomic regions to the human regions on chromosomes 6, 20, 16 and 14 respectively, as shown in Figure 1. This is a schematic diagram and not to scale. Colour coding indicates orthologous genes inferred by molecular phylogenetics (see additional files). Numbers at the ends of each line indicate chromosome number, or, where this is not available, scaffold number, with the latter indicated by S or NW. Numbers above lines indicate approximate distance in Kb between genes. A parallel red line indicates gaps in the sequence, while breaks in the sequence are indicated by double vertical black lines at the site of inversions. Double vertical red lines indicate separate contigs that we placed on a line due to their gene content; this does not imply they have been shown to be physically linked. Dashed boxes represent presence of a gene but no linkage information. Black circles indicate scaffold ends.
Figure 3. A model for gene duplication and loss in the Fox cluster loci during vertebrate evolution. Two initial rounds of duplication of the whole region are inferred to have occurred by the base of bony vertebrates, and this is consistent with both the 2R hypothesis and multiple block duplications. Considerable gene loss is then inferred before the radiation of bony vertebrates. Subsequent losses and inversions in different vertebrate lineages are indicated on the tree, with capital letters indicating the paralogon (nomenclature as shown in Figures 1 and 2) affected. A third round of genome duplication (3R) is indicated in the teleosts.
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