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Classification and nomenclature of all human homeobox genes.

Holland PW, Booth HA, Bruford EA - BMC Biol. (2007)

Bottom Line: Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development.We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. peter.holland@zoo.ox.ac.uk.

ABSTRACT

Background: The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.

Results: We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.

Conclusion: We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.

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Maximum likelihood phylogenetic tree of human PRD-class homeodomains. Arbitrarily rooted phylogenetic tree of human PRD-class homeodomains constructed using the maximum likelihood method. Bootstrap values supporting internal nodes with over 70% are shown. Homeodomain sequences derived from pseudogenes are excluded, as are the partial homeodomains of PAX2, PAX5 and PAX8, and the HOPX homeodomain because its extremely divergent sequence destabilizes the overall tree topology. Roman numeral suffixes are used to distinguish multiple homeodomains encoded by a single Dux-family gene. In this tree Dux-family homeodomains are not monophyletic, even within the same gene; however, monophyly is recovered by neighbor-joining analysis (Additional file 4). Detailed relationships between different gene families should not be inferred from this tree.
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Figure 2: Maximum likelihood phylogenetic tree of human PRD-class homeodomains. Arbitrarily rooted phylogenetic tree of human PRD-class homeodomains constructed using the maximum likelihood method. Bootstrap values supporting internal nodes with over 70% are shown. Homeodomain sequences derived from pseudogenes are excluded, as are the partial homeodomains of PAX2, PAX5 and PAX8, and the HOPX homeodomain because its extremely divergent sequence destabilizes the overall tree topology. Roman numeral suffixes are used to distinguish multiple homeodomains encoded by a single Dux-family gene. In this tree Dux-family homeodomains are not monophyletic, even within the same gene; however, monophyly is recovered by neighbor-joining analysis (Additional file 4). Detailed relationships between different gene families should not be inferred from this tree.

Mentions: It is much more difficult to propose a rigorous evolutionary definition for the rank of gene class. Every attempt to classify genes above the level of gene family involves a degree of arbitrariness. We define gene classes by taking two principal criteria into account. First, gene classes should ideally be monophyletic assemblages of gene families. To identify probable monophyletic groups of gene families, we conducted molecular phylogenetic analyses of homeodomain sequences, and looked for sets of gene families that group together stably, regardless of the precise composition of the dataset used (Figures 1, 2, 3; Additional files 3, 4, 5). Some gene families were difficult to place from sequence data alone, and were found in different gene classes (or subclasses) depending on the precise dataset analyzed or the phylogenetic method employed. This is perhaps not surprising as trees that encompass many homeobox genes can only be built with a short sequence alignment (the homeodomain); under these conditions, phylogenetic trees can only be used as a guide to possible classification, not the absolute truth. In ambiguous cases, we used the chromosomal location of genes to guide possible resolution between alternative hypotheses. Second, some homeobox gene classes can be characterized by the presence of additional protein domains outside of the homeodomain [2]. Recognized protein domains associated with homeodomains include the PRD domain, LIM domain, POU-specific domain, POU-like domain, SIX domain, various MEINOX-related domains, the CUT domain, PROS domain, and various ZF domains [2].


Classification and nomenclature of all human homeobox genes.

Holland PW, Booth HA, Bruford EA - BMC Biol. (2007)

Maximum likelihood phylogenetic tree of human PRD-class homeodomains. Arbitrarily rooted phylogenetic tree of human PRD-class homeodomains constructed using the maximum likelihood method. Bootstrap values supporting internal nodes with over 70% are shown. Homeodomain sequences derived from pseudogenes are excluded, as are the partial homeodomains of PAX2, PAX5 and PAX8, and the HOPX homeodomain because its extremely divergent sequence destabilizes the overall tree topology. Roman numeral suffixes are used to distinguish multiple homeodomains encoded by a single Dux-family gene. In this tree Dux-family homeodomains are not monophyletic, even within the same gene; however, monophyly is recovered by neighbor-joining analysis (Additional file 4). Detailed relationships between different gene families should not be inferred from this tree.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211742&req=5

Figure 2: Maximum likelihood phylogenetic tree of human PRD-class homeodomains. Arbitrarily rooted phylogenetic tree of human PRD-class homeodomains constructed using the maximum likelihood method. Bootstrap values supporting internal nodes with over 70% are shown. Homeodomain sequences derived from pseudogenes are excluded, as are the partial homeodomains of PAX2, PAX5 and PAX8, and the HOPX homeodomain because its extremely divergent sequence destabilizes the overall tree topology. Roman numeral suffixes are used to distinguish multiple homeodomains encoded by a single Dux-family gene. In this tree Dux-family homeodomains are not monophyletic, even within the same gene; however, monophyly is recovered by neighbor-joining analysis (Additional file 4). Detailed relationships between different gene families should not be inferred from this tree.
Mentions: It is much more difficult to propose a rigorous evolutionary definition for the rank of gene class. Every attempt to classify genes above the level of gene family involves a degree of arbitrariness. We define gene classes by taking two principal criteria into account. First, gene classes should ideally be monophyletic assemblages of gene families. To identify probable monophyletic groups of gene families, we conducted molecular phylogenetic analyses of homeodomain sequences, and looked for sets of gene families that group together stably, regardless of the precise composition of the dataset used (Figures 1, 2, 3; Additional files 3, 4, 5). Some gene families were difficult to place from sequence data alone, and were found in different gene classes (or subclasses) depending on the precise dataset analyzed or the phylogenetic method employed. This is perhaps not surprising as trees that encompass many homeobox genes can only be built with a short sequence alignment (the homeodomain); under these conditions, phylogenetic trees can only be used as a guide to possible classification, not the absolute truth. In ambiguous cases, we used the chromosomal location of genes to guide possible resolution between alternative hypotheses. Second, some homeobox gene classes can be characterized by the presence of additional protein domains outside of the homeodomain [2]. Recognized protein domains associated with homeodomains include the PRD domain, LIM domain, POU-specific domain, POU-like domain, SIX domain, various MEINOX-related domains, the CUT domain, PROS domain, and various ZF domains [2].

Bottom Line: Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development.We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Zoology, University of Oxford, South Parks Road, Oxford, OX1 3PS, UK. peter.holland@zoo.ox.ac.uk.

ABSTRACT

Background: The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.

Results: We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.

Conclusion: We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.

Show MeSH
Related in: MedlinePlus