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Do Human Chromosomal Bands 16p13 and 22q11-13 Share Ancestral Origins?

1998; Elsevier BV; Volume: 63; Issue: 4 Linguagem: Inglês

10.1086/302044

1537-6605

Rachel H. Giles, Hans G. Dauwerse, Gert‐Jan B. van Ommen, Martijn H. Breuning,

Chromosomal and Genetic Variations

To the Editor: Ancient duplications and rearrangements within a genome are believed to be important mechanisms of evolution. Although most duplications are of gene segments, single genes, or chromosomal segments, molecular evidence has been gathered suggesting that whole-genome duplication has facilitated evolution in yeast (Wolfe and Shields Wolfe and Shields, 1997Wolfe KH Shields DC Molecular evidence for an ancient duplication of the entire yeast genome.Nature. 1997; 387: 708-713Crossref PubMed Scopus (1325) Google Scholar). Identifying these duplicated genomic areas can be valuable not only for understanding the timing and nature of evolutionary events; additionally, this information can greatly facilitate the pinpointing of novel (disease-related) genes by positional cloning techniques. While mapping and cloning the human gene encoding the CREB-binding protein (CBP, encoded by the CREBBP gene) on chromosome band 16p13.3 (Giles et al. Giles et al., 1997bGiles RH Petrij F Dauwerse JG den Hollander AI Lushnikova T van Ommen G-JB Goodman RH et al.Construction of a 1.2-Mb contig surrounding, and molecular analysis of, the human CREB-binding protein (CBP/CREBBP) gene on chromosome 16p13.3.Genomics. 1997b; 42: 96-114Crossref PubMed Scopus (60) Google Scholar), we noticed an emerging pattern concerning the genomic relationship between this chromosome band and a region of chromosome 22q. CBP exhibits extensive homology to the adenovirus E1A–associated protein p300, whose gene has been mapped to human chromosome band 22q13 (Eckner et al. Eckner et al., 1994Eckner R Ewen ME Newsome D Gerdes M DeCaprio JA Lawrence JB Livingston DM Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.Genes Dev. 1994; 8: 869-884Crossref PubMed Scopus (902) Google Scholar; Lundblad et al. Lundblad et al., 1995Lundblad JR Kwok RPS Laurance ME Harter ML Goodman RH Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP.Nature. 1995; 374: 85-88Crossref PubMed Scopus (523) Google Scholar). At that time we noted with interest that the heme oxygenase-1 (HMOX1) gene, just centromeric of CREBBP on 16p13.3, has a paralogue mapping to chromosome band 22q12, heme oxygenase-2 (HMOX2; Kutty et al. Kutty et al., 1994Kutty RK Kutty G Rodriguez IR Chader GJ Wiggert B Chromosomal localization of the human heme oxygenase genes: heme oxygenase-1 (HMOX1) maps to chromosome 22q12 and heme oxygenase-2 (HMOX2) maps to chromosome 16p13.3.Genomics. 1994; 20: 513-516Crossref PubMed Scopus (92) Google Scholar). Our interest was further piqued when the molecular defect in families with carbohydrate-deficient glycoprotein type I syndrome (CDG1) was determined to be caused by mutations in the phosphomannomutase 2 gene (PMM2) on 16p13 (Matthijs et al. Matthijs et al., 1997aMatthijs G Schollen E Pardon E Veiga-Da-Cuhna M Jaeken J Cassiman J-J van Schaftingen E Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome).Nat Genet. 1997a; 16: 88-92Crossref PubMed Scopus (286) Google Scholar); the same investigators had previously mapped the first phosphomannomutase gene (PMM1) to 22q13 (Matthijs et al. Matthijs et al., 1997bMatthijs G Schollen E Pirard M Budarf ML van Schaftingen E Cassiman J-J PMM (PMM1), the human homologue of SEC53 or yeast phosphomannomutase, is localized on chromosome 22q13.Genomics. 1997b; 40: 41-47Crossref PubMed Scopus (52) Google Scholar). Sequence comparison at the amino acid level revealed that homologies between these paralogous proteins are high: homology between CBP and p300 is 63% (Arany et al. Arany et al., 1995Arany Z Newsome D Oldread E Livingston DM Eckner R A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.Nature. 1995; 374: 81-84Crossref PubMed Scopus (483) Google Scholar), that between PMM1 and PMM2 is 66% (Matthijs et al., 1997aMatthijs G Schollen E Pardon E Veiga-Da-Cuhna M Jaeken J Cassiman J-J van Schaftingen E Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome).Nat Genet. 1997a; 16: 88-92Crossref PubMed Scopus (286) Google Scholar), and that between HMOX1 and HMOX2 is 74% (authors' observation). Subsequent examination of genome databases (e.g., OMIM) resulted in six additional sets of paralogues mapping to chromosomes 16p13 and 22q11-13, although the extent of homology between these paralogue sets is not known (table 1). YAC contigs connecting outlying genes of each paralogous cluster, CREBBP to MYH11 on chromosome 16 and the CRYB genes to PMM1 on chromosome 22, suggest that the extent of the redundant area presented here is ∼12–14 Mb. Furthermore, CREBBP and MYH11 are also thought to be near the borders for the conserved synteny group in mouse chromosome 16 (Doggett et al. Doggett et al., 1996Doggett NA Breuning MH Callen DF Report of the Fourth International Workshop on Human Chromosome 16 Mapping 1995.Cytogenet Cell Genet. 1996; 72: 271-293Crossref PubMed Google Scholar).Table 1Paralogous Genes Mapped to Chromosome Bands 16p13 and 22q11-13ParaloguesGene/ChromosomeaListed from telomere to centromereGene /ChromosomeDescriptionSSTR5/16p13.3SSTR3/22q13.1Somatostatin receptorsCREBBP/16p13.3p300/22q13Transcriptional cofactorsCSNK2A1′/16p13.3CSNK1E/22q12-13Casein kinase isoformsUBE2I/16p13.3UBE2L3/22q11.2-13.1Ubiquitin-conjugating enzymesPMM2/16p13.3PMM1/22q13.1Phosphomannomutase isoformsHMOX2/16p13.3HMOX1/22q12Heme oxygenase isoformsMYH11/16p13.13-13.12MYH9/22q11.2Myosin heavy-chain subunitsCRYM/16p13.11-12.3CRYBB1/22q11.2-12.1Crystallin isoformsCRYB2/22q11.2-12.2CRYB3/22q11.2-12.2CRYBA4/22q11.2-13.1IL4R/16p12IL2RB/22q12Interleukin receptorsa Listed from telomere to centromere Open table in a new tab We propose that the existence of these paralogous sets suggests that chromosome bands 16p13 and 22q11-13 share ancestral origins and that at some point a large-scale duplication gave rise to this second set of genes. It is well established that such duplicated regions exist (Lundin Lundin, 1993Lundin LG Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse.Genomics. 1993; 16: 1-19Crossref PubMed Scopus (395) Google Scholar; Holland et al. Holland et al., 1994Holland PW Garcia-Fernandez J Williams NA Sidow A Gene duplications and the origins of vertebrate development.Dev Suppl. 1994; : 125-133PubMed Google Scholar), and a catalogue of putative paralogous regions can be found on-line (Database of Duplicated Human Chromosomal Regions). This database suggests two duplicated regions for areas of 16p: a well-documented gene cluster on chromosome band 16p11.1, which shares high homology with a locus on Xq28 (Eichler et al. Eichler et al., 1996Eichler EE Lu F Shen Y Antonacci R Jurecic V Doggett NA Moyzis RK et al.Duplication of a gene-rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution.Hum Mol Genet. 1996; 5: 899-912Crossref PubMed Scopus (123) Google Scholar), and a region of 16p13, which resembles 19p13, although no specific genes are named. A hypothesis set forth by Ohno (Ohno, 1993Ohno S Patterns in genome evolution.Curr Opin Genet Dev. 1993; 3: 911-914Crossref PubMed Scopus (57) Google Scholar) suggests that at the stage of fish, the mammalian ancestral genome underwent tetraploid duplication. Although certain aspects of this hypothesis are not universally accepted, most scientists agree that the fourfold increase, in the number of genes, between invertebrates and vertebrates implies at least two rounds of genome duplication (Aparicio Aparicio, 1998Aparicio S Exploding vertebrate genomes.Nat Genet. 1998; 18: 301-303Crossref PubMed Scopus (19) Google Scholar). Paralogues such as the HOX-gene clusters, which are situated at four distinct chromosomal loci, bolster this hypothesis. If the gene redundancy observed on chromosomes 16 and 22 is a result of Ohno's proposed ancestral event, then one might expect that two additional loci exist in the human genome that shares at least partial homology. CBP and p300 do, in fact, count two additional protein family members, p270 (Dallas et al. Dallas et al., 1997Dallas PB Yaciuk P Moran E Characterization of monoclonal antibodies raised against p300: both p300 and CBP are present in intracellular TBP complexes.J Virol. 1997; 71: 1726-1731Crossref PubMed Google Scholar) and p400 (Barbeau et al. Barbeau et al., 1994Barbeau D Charbonneau R Whalen SG Bayley ST Branton PE Functional interactions within adenovirus E1A protein complexes.Oncogene. 1994; 9: 359-373PubMed Google Scholar), although the genes for these proteins have not yet been mapped. Candidate regions, however, can be inferred from the literature. For example, clues can be taken from the somatic translocation t(8;16)(p11;p13.3), associated with acute myeloid leukemia, which disrupts the CREBBP gene and fuses it to a gene on chromosome 8, called "MOZ" (Borrow et al. Borrow et al., 1996Borrow J Stanton Jr, VP Andresen JM Becher R Behm FG Chaganti RSK Civin CI et al.The translocation t(8;16)(p11;p13) of acute myeloid leukemia fuses a putative acetyl transferase to the CREB-binding protein.Nat Genet. 1996; 14: 33-41Crossref PubMed Scopus (617) Google Scholar; Giles et al. Giles et al., 1997aGiles RH Dauwerse JG Higgins C Petrij F Wessels JW Beverstock GC Döhner H et al.Detection of CBP rearrangements in acute myelogenous leukemia with t(8;16).Leukemia. 1997a; 11: 2087-2096Crossref PubMed Scopus (58) Google Scholar). Phenotype-identical variants of the t(8;16) have been described: the t(8;22)(p11;q13), postulated to fuse p300 to MOZ, as well as t(6;8)(q27;p11) (Tanzer et al. Tanzer et al., 1988Tanzer J Brizard A Guilhot F Benz-Lemoine E Dreyfus B Lessard M Herchkovitch C et al.La leucémie aigüe à translocation (8;16).Nouv Rev Fr Hematol. 1988; 30: 83-87PubMed Google Scholar), t(8;19)(p11;q13.2) (Tanzer et al. Tanzer et al., 1988Tanzer J Brizard A Guilhot F Benz-Lemoine E Dreyfus B Lessard M Herchkovitch C et al.La leucémie aigüe à translocation (8;16).Nouv Rev Fr Hematol. 1988; 30: 83-87PubMed Google Scholar; Stark et al. Stark et al., 1995Stark B Resnitzky P Jeison M Luria D Blau O Avigad S Shaft D et al.A distinct subtype of M4/M5 acute myeloblastic leukemia (AML) associated with t(8;16)(p11;p13), in a patient with the variant t(8;19)(p11;q13): case report and review of the literature.Leuk Res. 1995; 19: 367-379Abstract Full Text PDF PubMed Scopus (48) Google Scholar), t(8;14)(p11;q11.1) (Slovak et al. Slovak et al., 1991Slovak ML Nemana L Traweek ST Stroh JA Acute monoblastic leukemia (FAB-M5b) with t(8;14)(p11;q11.1).Cancer Genet Cytogenet. 1991; 56: 237-242Abstract Full Text PDF PubMed Scopus (13) Google Scholar), and t(3;8;17)(q27;p11;q12) (Bertheas et al. Bertheas et al., 1989Bertheas MF Jaubert J Vasselon C Reynaud J Pomier G Le Petit JC Hagemeijer A et al.A complex t(3;8;17) involving breakpoint 8p11 in a case of M5 acute nonlymphocytic leukemia with erythrophagocytosis.Cancer Genet Cytogenet. 1989; 42: 67-73Abstract Full Text PDF PubMed Scopus (13) Google Scholar). If it is assumed that these phenotypically similar leukemias all fuse MOZ to genes situated at the breakpoints on chromosome bands 3q27, 6q27, 14q11.1, 17q12, or 19q13.2, then these loci become good candidates for the p270/p400 genes—and, thus, for additional redundant clusters. Interestingly, two of these loci do harbor additional gene-family members paralogous to those mapping to 16p13 and 22q11-q13 (table 1): the SSTR1, UBE2L1, MYH6, and MYH7 genes map to chromosome bands 14q11-q13, whereas the SSTR2, CSNK1D, and CRYBA1 genes map to chromosome 17q11-q25. The gene-mapping data coupled with the leukemia breakpoint locations strongly suggest that these gene families have arisen by tetrapoidization with members on chromosomes 14q, 16p, 17q, and 22q. Genetic redundancy is potentially of great relevance to organismal evolution, since it may protect organisms from potentially harmful mutations and may provide a pool of diverse yet functionally similar proteins for further evolution. Transcription factors such as CBP and p300 are thought particularly to "profit" from redundancy, as demonstrated by recent knockout mouse studies, which show that the combined dose of CBP and p300 is essential for survival (reviewed by Giles Giles, 1998Giles RH CBP/p300 transgenic mice.Trends Genet. 1998; 14: 214Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar). The existence of these duplicated gene clusters is not just a matter of redundancy; in the cases of CBP/p300 and PMM1/PMM2, the proteins have been shown to be functionally divergent. Where in vitro experiments suggest almost complete functional redundancy, CBP and p300 are clearly not physiologically interchangeable (reviewed by Giles et al. Giles et al., 1998Giles RH Peters DJM Breuning MH Conjunction dysfunction: CBP/p300 in human disease.Trends Genet. 1998; 14: 178-183Abstract Full Text Full Text PDF PubMed Scopus (345) Google Scholar); inactivating germ-line mutations of one copy of the CREBBP gene cause the Rubinstein-Taybi syndrome (Petrij et al. Petrij et al., 1995Petrij F Giles RH Dauwerse JG Saris JJ Hennekam RC Masuno M Tommerup N et al.Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP.Nature. 1995; 376: 348-351Crossref PubMed Scopus (974) Google Scholar). Likewise, mutations in PMM2, but not those in PMM1, result in CDG1 (Matthijs et al. Matthijs et al., 1997aMatthijs G Schollen E Pardon E Veiga-Da-Cuhna M Jaeken J Cassiman J-J van Schaftingen E Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome).Nat Genet. 1997a; 16: 88-92Crossref PubMed Scopus (286) Google Scholar; Schollen et al. Schollen et al., 1998Schollen E Pardon E Heykants L Renard J Doggett NA Callen DF Cassiman J-J et al.Comparative analysis of the phosphomannomutase genes PMM1, PMM2 and PMM2Ψ: the sequence variation in the processed pseudogene is a reflection of the mutations found in the functional gene.Hum Mol Genet. 1998; 7: 157-164Crossref PubMed Scopus (36) Google Scholar). Accession numbers and URLs for data in this article are as follows: Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim Database of Duplicated Human Chromosomal Regions, http://www.cib.nig.ac.jp/dda/timanish/dup.html