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BMC Genomics
2005 Nov 23;6:167. doi: 10.1186/1471-2164-6-167.
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Analysis of vertebrate genomes suggests a new model for clade B serpin evolution.
Kaiserman D
,
Bird PI
.
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BACKGROUND: The human genome contains 13 clade B serpin genes at two loci, 6p25 and 18q21. The three genes at 6p25 all conform to a 7-exon gene structure with conserved intron positioning and phasing, however, at 18q21 there are two 7-exon genes and eight genes with an additional exon yielding an 8-exon structure. Currently, it is not known how these two loci evolved, nor which gene structure arose first--did the 8-exon genes gain an exon, or did the 7-exon genes lose one? Here we use the genomes of diverse vertebrate species to plot the emergence of clade B serpin genes and to identify the point at which the two genomic structures arose.
RESULTS: Analysis of the chicken genome indicated the presence of a single clade B serpin gene locus, containing orthologues of both human loci and both genomic structures. The frog genome and the genomes of three fish species presented progressively simpler loci, although only the 7-exon structure could be identified. The Serpinb12 gene contains seven exons in the frog genome, but eight exons in chickens and humans, indicating that the additional exon evolved in this gene.
CONCLUSION: We propose a new model for clade B serpin evolution from a single 7-exon gene (either Serpinb1 or Serpinb6). An additional exon was gained in the Serpinb12 gene between the tetrapoda and amniota radiations to produce the 8-exon structure. Both structures were then duplicated at a single locus until a chromosomal breakage occurred at some point along the mammalian lineage resulting in the two modern loci.
Figure 1. Distribution of clade B serpin genes in vertebrate genomes. A dendrogram showing relationships between vertebrate species with clade B serpin gene loci. The genes identified within each genome are indicated on the right without the SERPIN root designation. Multiple loci are delineated by square brackets, while genes identified in EST databases, but not in the genome, are in round brackets. * due to the incomplete nature of the sequencing data, the structure of the rabbit (Oryctolagus cuniculus) loci could not be established. Branch lengths are not to scale.
Figure 2. Comparison of frog, chicken and human clade B serpin loci. The structure of the serpin locus in frog, chicken and human is shown with 7-exon serpin genes in green, 8-exon serpin genes in red and non-serpin genes in black. Gene structure could not be predicted for Serpinb10a (blue). Arrows indicate the direction of transcription. Orthologous genes with strong RCL conservation are linked with solid lines, dotted lines denote inter-species orthologues with weak RCL homology. (B) The amino acid sequences of human, chicken and frog clade B serpins were aligned with human antithrombin (SERPINC1) and a Neighbour-Joining tree constructed (gapped positions removed, 1000 bootstraps) to show evolutionary relationships. Scale bar indicates the number of substitutions at each site. Node colour indicates the bootstrap value (black >75%, grey 50–75%, white <50%). Genes are named without the SERPIN root. hsa = Homo sapiens; gga = Gallus gallus; xtr =
Xenopus tropicalis.
Figure 3. A new mechanism of clade B serpin gene expansion. (A) A new model for evolution of two clade B serpin loci in mammals, from a single locus of 4 genes. A series of intrachromosomal duplications results in 13 genes, followed by chromosomal breakage to yield two loci. Two previously proposed mechanisms based on duplication of an ancestral locus as described by (B) Bartuski et al. [14]; and (C) Scott et al. [15]. Arrows represent gene duplication events. Black boxes indicate genes displaying the 8-exon structure, white boxes are 7-exon genes. Genes are named without the SERPIN root. Diagram not to scale.
Figure 4. Distribution of clade B serpin ESTs in fish. A dendrogram of fish species is shown with clade B serpins ESTs shown on the right in brackets. The tetrapoda lineage is also indicated, with the simplest locus (Xenopus tropicalis) shown for comparison. Genes are named without the SERPIN root. The relative timing of genome duplication and subsequent gene loss within ray finned fish are shown as well as the composition of the loci after each event. Asterisk indicates an EST for which only the genus name was given.
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