how many hox genes do humans have

10.1073/pnas.0836141100. 10.1016/S0925-4773(99)00318-4. Curr Biol. The genes form a distinct grouping even if the POU-specific domain is disregarded phylogenetic analyses of homeodomains recover the POU class as a monophyletic group (Figure 3; Additional files 1, 2 and 5). 2005, 13: 601-607. In ambiguous cases, we used the chromosomal location of genes to guide possible resolution between alternative hypotheses. TGIF2P1 [GeneID: 126826], TGIF2P2 [GeneID: 100009674], TGIF2P3 [GeneID: 100009672] and TGIF2P4 [GeneID: 100009673]. Hum Mol Genet. There is confusion as to whether this should be split into two gene families, because invertebrate homologs generally group with PAX6 in phylogenetic analyses and not as an outgroup to the two genes as might be expected. The mouse Rhox cluster was first described as comprising twelve X-linked homeobox genes, all selectively expressed in reproductive tissues [47]. These include genes lost from human, as well genes known to have undergone unusually rapid evolution in Drosophila. These values are not shown if the gene family does not form a monophyletic group in phylogenetic analyses (in which case n/a is written) or if an invertebrate homolog could not be found. POU5F1P7 and POU5F1P8 are partial integrants of POU5F1 mRNA excluding the homeobox POU5F1P7 covers part of the 3' untranslated region and POU5F1P8 a short region around the start codon. Discounting the rather aberrant case of the Hox clusters, this region of the long arm of chromosome 10 is the most homeobox-rich region of the human genome. Article PubMed Pseudogenes were recognized as those genomic regions with similarity to non-repetitive DNA sequences of the parent gene, even if aligning to only part of the locus. The highly repetitive DUX1 to DUX5 sequences are also not shown, as these have undergone secondary amplification and are also most likely non-functional (see above). 10.1007/s004270050250. Of the nine human genes possessing a paired-box (PAX1 to PAX9), only four also contain a complete homeobox (PAX3, PAX7, PAX4 and PAX6). The classification scheme proposed may be widely applicable to homeobox genes from other animals. MNX1 [Entrez Gene ID: 3110] is the only member of the Mnx gene family in the human genome. Each gene family has two human members and dates to a single ancestral gene in the most recent common ancestor of bilaterians [68, 69]. 2004, 84: 229-238. Arbitrarily rooted phylogenetic tree of all human plus selected protostome and cnidarian homeodomains constructed using the neighbor-joining (NJ) method. 2006, 295: 40-51. 10.1101/gad.11.10.1207. As noted earlier, phylogenetic analyses of homeodomains does not recover the ZF class as a monophyletic group (Figure 3; Additional files 1, 2 and 5). Detailed relationships between different gene families should not be inferred from this tree. Castro LFC, Holland PWH: Chromosomal mapping of ANTP class homeobox genes in amphioxus: piecing together ancestral genomes. HDX [Entrez Gene ID: 139324]. For example, Hox genes are found in many animals (including flies and humans) and designate where the head goes and which regions of the body grow appendages. Hox genes likely evolved in animals long ago, because many species have Hox genes which are identical. Development. The total number of homeobox sequences in the human genome is higher than 300 for two reasons. This gene was previously known as CXorf43. 1997, 11: 1207-1225. The POU-like domain, as its name indicates, is weakly similar in sequence to the POU-specific domain [64]; more importantly, it has nearly the same three-dimensional structure and mode of DNA binding as the POU-specific domain [65]. Despite the numerous discrepancies, the common principle of classification is the same. The steps that Hox genes undergo to regulate vvI1+2 can inform how Hox genes regulate other DNA, not just in fruit flies but beyond including in vertebrates, such as mammals, and even humans. This very well known gene family was originally considered to contain human OTX1 and OTX2 (and their mouse orthologs) and the Drosophila otd gene [43]. The family includes one gene in the human genome: MNX1 (formerly HLXB9), and two genes in the chicken genome: Mnx1 (formerly HB9) and Mnx2 (formerly MNR2). This gene was previously known as IPF1; we rename it PDX1 because the majority of published studies use this as the gene symbol. For example, there is uncertainty as to whether there were one or two Dlx (distal-less) genes in the most recent common ancestor of bilaterians; however it is common practice to refer to a single Dlx gene family [18]. 10.1016/j.cell.2004.12.022. 10.1111/j.1742-4658.2006.05186.x. Nat Genet. The PROS domain is a DNA-binding domain of approximately 100 amino acids [77]. 10.1073/pnas.1834010100. Six very divergent gene families were undetected by this method but found by text searching: Hopx, Adnp, Tshz, Zeb, Zhx/Homez and Cers. The prefix PEPP is not suitable as it is used for numerous aminopeptidase P-encoding genes. Disorders of limb formation, such as hand-foot-genital syndrome, have been traced to mutations in HOXA13 and HOXD13. Mol Gen Genom. They are a piece of the complicated puzzle that separate man from animal and from one another. EB contributed to gene nomenclature revisions, discussed these with the research community and databases, and implemented the agreed changes. Detailed relationships between different gene families should not be inferred from this tree. Mouse models will aid clinicians in identifying additional human Hox disorders. IRX4P1 [Entrez Gene ID: 100009671]. DUXB is described here (see below). Introduction How many legs does a fruit fly have? The same may also be true for the LIM class; alternatively the apparent polyphyly of LIM-class homeodomains could be a consequence of LIM domain loss or artefactual placement of some ZF-class homeodomains in phylogenetic analyses (Figure 3; Additional file 5). 2002, 10: 1129-1137. 10.1007/s00335-005-0138-4. This family of genes is responsible for determining the general body plan, such as the number of body segments of an animal, the number and placement of appendages, and animal head-tail directionality. Dux gene family. We have identified a previously undescribed pseudogene from the Otx gene family (OTX2P1), and argue that the majority of Dux-family sequences are pseudogenes. 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]. (PDF 17 KB), Additional file 5: Neighbor-joining phylogenetic tree of human homeodomains excluding ANTP and PRD classes, for comparison to maximum likelihood tree. Mo Bio Evol. We designate this previously undescribed sequence OTX2P1 because it is clearly a retrotransposed pseudogene of OTX2. 10.1016/S0378-1119(02)01087-9. Genome Res. [http://www.compbio.dundee.ac.uk/Software/JPred/jpred.html], Ensembl Genome Browser. The loci are also classified into a simple hierarchical scheme, comprising 102 gene families within eleven gene classes. Experimenting With Embryos: Identifying The Human Hox Genes Brglin TR: The PBC domain contains a MEINOX domain: coevolution of Hox and TALE homeobox genes?. We favor placement within the PRD class because the NOBOX homeodomain has higher sequence identity with PRD-class homeodomains (up to 55%) than with ANTP-class homeodomains (up to 46%). The Hox genes are an evolutionarily conserved family of genes, which encode a class of important transcription factors that function in numerous developmental processes. We have revised the nomenclature of two CUT-class genes (CUX1 and CUX2). Studies of mutations in other homeobox genes suggest that mutation to leucine alters transcriptional activity of a homeodomain protein [55]. Gene. We have identified a total of 14 ZF-class homeobox genes in the human genome (Tables 1 and 4), which we have placed in five gene families (Adnp, Tshz, Zeb, Zfhx and Zhx/Homez). This gene was previously known as BAPX1; we rename it NKX3-2 to show that it is a member of the Nk3 gene family. Phylogenetic analyses place this gene family firmly within the NKL subclass (Figure 1; Additional file 3), but chromosomal positions (on the Hox chromosomes 2, 7 and 17) place it within the HOXL subclass (Figure 4). 1991, 2: 435-445. Using exhaustive database screening, followed by manual examination of sequences, we identified 300 homeobox loci in the human genome. Exon-intron structures of novel loci were deduced by comparison between genomic sequence and cDNA, EST or retrotransposed pseudogene sequences, as previously described [21]. Maximum likelihood phylogenetic tree of human homeodomains excluding ANTP and PRD classes. The human gene is the ortholog of mouse Sebox based on their locations in syntenic chromosomal regions (17q11.2 and 11B5 respectively) and presence of the same intron positions. It. Gabrils J, Beckers M-C, Ding H, De Vriese A, Plaisance S, van der Maarel SM, Padberg GW, Frants RR, Hewitt JE, Collen D, et al: Nucleotide sequence of the partially deleted D4Z4 locus in a patient with FSHD identifies a putative gene within each 3.3 kb element. Genes belonging to the TALE class encode proteins with various domains outside of the atypical homeodomain. We favor placement in the PRD class for three reasons. Chen F, Kook H, Milewski R, Gitler AD, Lu MM, Li J, Nazarian R, Schnepp R, Jen K, Biben C, et al: Hop is an unusual homeobox gene that modulates cardiac development. Gene. 10.1007/s00239-006-0023-0. Human HOX disorders show variation in inheritance, pathogenesis and expressivity. 10.1002/1521-1878(200007)22:7<616::AID-BIES4>3.0.CO;2-R. Gallardo ME, Lopez-Rios J, Fernaud-Espinosa I, Granadino B, Sanz R, Ramos C, Ayuso C, Seller MJ, Brunner HG, Bovolenta P, et al: Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies. 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 designate this previously unannotated sequence IRX4P1 because it is clearly a retrotransposed pseudogene of IRX4. Highly conserved 60-amino acid sequence Binds to DNA and switches other genes on or off What is a hox gene? Human HOX gene disorders - PubMed This definition has been made explicitly in previous work [2, 6] but is actually a principle that has been in widespread, but rather inconsistent, use for over a decade [15]. The prefix PEPP cannot be approved for reasons noted above. volume5, Articlenumber:47 (2007) This is done by gradients of mRNAs and proteins encoded by the mother's genes and placed in the egg by her. Mol Cell. Nature. These are the ParaHox cluster (GSX1, PDX1, CDX2) on chromosome 13, and four sets of NKL-subclass genes on 2p/8p (split), 4p, 5q and 10q, hypothesized to be derived from an ancestral array by duplication [26, 33]. This gene was previously known as OG9X with SEBOX as the alternative symbol; we favor SEBOX because the OG prefix was originally used for several unrelated homeobox genes. It is much more difficult to propose a rigorous evolutionary definition for the rank of gene class. Genome Res. PubMed Nonetheless, at the present time the 102 gene families provide a sound framework for the study of human homeobox genes. The human genome contains three homeobox genes at Xq24 that are clearly members of the Rhox gene family based on sequence identity, molecular phylogenetics, intron positions and chromosomal location. . The finished human genome sequence (build 35.1) was subjected to a series of tBLASTn searches [85, 86] using known homeodomain sequences from the ANTP, PRD, LIM, POU, HNF, SINE, TALE, CUT, PROS and ZF classes. 1989, 5: 164-166. 1997, 25: 4173-4180. 2003, 5: 459-465. In phylogenetic analyses, PROS-class homeodomains are situated on a long branch, very distant from other classes (Figure 3; Additional files 1, 2 and 5). In chordates, genome duplications generated multiple clusters (top). & Bruford, E.A. When Hox genes were first cloned and shown to encode homeodomain-containing proteins ( Akam, 1989; Regulski et al., 1985 ), researchers initially speculated that Hox proteins would bind and regulate the correct subset of target genes according to the DNA recognition properties of their homeodomains. Homeodomain sequences derived from pseudogenes are excluded. Plouhinec J-L, Sauka-Spengler T, Germot A, Le Mentec C, Cabana T, Harrison G, Pieau C, Sire J-Y, Vron G, Mazan S: The mammalian Crx genes are highly divergent representatives of the Otx5 gene family, a gnathostome orthology class of orthodenticle-related homeogenes involved in the differentiation of retinal photoreceptors and circadian entrainment. Members of this gene family are characterized by the presence of two closely-linked homeobox motifs. There are other concentrations of ANTP-class genes away from the Hox clusters. PubMed Central Here we favor placement of the Dlx gene family within the NKL subclass due to strong phylogenetic support. ALX1 [Entrez Gene ID: 8092] is the first of three human members of the Alx gene family. 10.1038/31933. This gene was previously known as ZNF508; we rename it ADNP2 to reflect its paralogous relationship to ADNP. In previous studies, the PRD class has been subdivided in several different ways, often based on identify of the amino acid at residue 50 in the homeodomain, for example S50, K50 and Q50. Google Scholar. J Biol Chem. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. NANOGP1 [Entrez Gene ID: 404635]. Cytogen Genome Res. Perhaps the most interesting case, however, is found on the tip of the long arm of chromosome 9, where there is a concentration of homeobox genes from disparate gene classes. 1996, 79: 920-929. Other details can be found in Table 2. Arbitrarily rooted phylogenetic tree of human PRD-class homeodomains constructed using the neighbor-joining method. Fourth, the LEUTX gene is located close to the PRD-class genes TPRX1, CRX, DPRX and DUXA on the distal end of the long arm of chromosome 19 (Figure 4). 2004, 5: 920-931. RHOXF1 [Entrez Gene ID: 158800] and RHOXF2 [Entrez Gene ID: 84528] are two of three human members of the Rhox gene family. The OTX2P1 sequence lacks introns, ends with a poly(A) tail, and harbors critical sequence alterations (including a three-nucleotide insertion introducing a stop codon into the deduced homeodomain). In theory, it is possible to recognize higher level associations above the level of the gene class, because the diversification of homeobox genes will have taken place by a continual series of gene duplication events. VENTXP5 [Entrez Gene ID: 442384]. The multiple homeodomains of Zfhx-family proteins and Zhx/Homez-family proteins are also dispersed in the tree, presumably artefactually. The figures exclude the repetitive DUX1 to DUX5 homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. The former name of PBXP1 did not indicate its transcript of origin. Nature. The alternative view, argued by Zhang et al [38], is that this locus is a functional retrogene. Trees were displayed using TreeExplorer [93]. Until this is shown more clearly we consider it to be a functional, but divergent, gene. Google Scholar. We designate this previously unnamed gene POU5F2 on the basis of clear orthology to the mouse Sprm1 gene, which has been assigned the second member of the Pou5 gene family [63]. BSX [Entrez Gene ID: 390259] is the only member of the Bsx gene family in the human genome. These associations may be remnants of common ancestry early in animal evolution. MacLean JA, Chen MA, Wayne CM, Bruce SR, Rao M, Meistrich ML, Macleod C, Wilkinson MF: Rhox: a new homeobox gene cluster. Int J Dev Biol. This gene has generated two retrotransposed pseudogenes: one at 2q11.2 and another at 12q24.33. Mol Cell Biol. Chromosomal distribution of human homeobox genes. 2004, 131: 1065-1073. The CUT domain is a DNA-binding domain of approximately 75 amino acids [75]. It is currently unclear if this gene family is derived from one or more genes in the common ancestor of bilaterians [18]. No cDNA or EST sequences have been reported for DUXB. VENTX [Entrez Gene ID: 27287] is the only functional member of the Ventx gene family in the human genome. 10.1074/jbc.R600010200. It should be noted that the established name of the Pknox gene family does not indicate orthology with Knox-family genes of plants. 10.1016/S0888-7543(03)00169-1. Following their initial discovery, a substantial amount of information has been gained regarding the roles Hox genes play in various physiologic and pathologic processes. These figures include three functional genes that possess partial homeobox sequences (PAX2, PAX5 and PAX8) and retrotransposed pseudogenes that correspond to only part of the original transcript, whether or not it includes the homeobox region or indeed any of the original coding region.
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