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Science 313 (5795): 1918-1922

Copyright © 2006 by the American Association for the Advancement of Science

Genomic Evolution of Hox Gene Clusters

Derek Lemons, and William McGinnis

Abstract: The family of Hox genes, which number 4 to 48 per genome depending on the animal, control morphologies on the main body axis of nearly all metazoans. The conventional wisdom is that Hox genes are arranged in chromosomal clusters in colinear order with their expression patterns on the body axis. However, recent evidence has shown that Hox gene clusters are fragmented, reduced, or expanded in many animals—findings that correlate with interesting morphological changes in evolution. Hox gene clusters also contain many noncoding RNAs, such as intergenic regulatory transcripts and evolutionarily conserved microRNAs, some of whose developmental functions have recently been explored.

Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093, USA.

*To whom correspondence should be addressed. E-mail: wmcginnis{at}

Deep conservation of cis-regulatory elements in metazoans.
I. Maeso, M. Irimia, J. J. Tena, F. Casares, and J. L. Gomez-Skarmeta (2013)
Phil Trans R Soc B 368, 20130020
   Abstract »    Full Text »    PDF »
The regulation of Hox gene expression during animal development.
M. Mallo and C. R. Alonso (2013)
Development 140, 3951-3963
   Abstract »    Full Text »    PDF »
Understanding the regulatory and transcriptional complexity of the genome through structure.
T. R. Mercer and J. S. Mattick (2013)
Genome Res. 23, 1081-1088
   Abstract »    Full Text »    PDF »
Structure, evolution and function of the bi-directionally transcribed iab-4/iab-8 microRNA locus in arthropods.
J. H. L. Hui, A. Marco, S. Hunt, J. Melling, S. Griffiths-Jones, and M. Ronshaugen (2013)
Nucleic Acids Res. 41, 3352-3361
   Abstract »    Full Text »    PDF »
Hox genes regulate the onset of Tbx5 expression in the forelimb.
C. Minguillon, S. Nishimoto, S. Wood, E. Vendrell, J. J. Gibson-Brown, and M. P. O. Logan (2012)
Development 139, 3180-3188
   Abstract »    Full Text »    PDF »
Genome-wide polycomb target gene prediction in Drosophila melanogaster.
J. Zeng, B. D. Kirk, Y. Gou, Q. Wang, and J. Ma (2012)
Nucleic Acids Res. 40, 5848-5863
   Abstract »    Full Text »    PDF »
A hierarchical model of the evolution of human brain specializations.
H. C. Barrett (2012)
PNAS 109, 10733-10740
   Abstract »    Full Text »    PDF »
Cis-regulation and conserved non-coding elements in amphioxus.
L. Beaster-Jones (2012)
Briefings in Functional Genomics
   Abstract »    Full Text »    PDF »
How much does the amphioxus genome represent the ancestor of chordates?.
A. Louis, H. Roest Crollius, and M. Robinson-Rechavi (2012)
Briefings in Functional Genomics 11, 89-95
   Abstract »    Full Text »    PDF »
An Independent Genome Duplication Inferred from Hox Paralogs in the American Paddlefish--A Representative Basal Ray-Finned Fish and Important Comparative Reference.
K. D. Crow, C. D. Smith, J.-F. Cheng, G. P. Wagner, and C. T. Amemiya (2012)
Genome Biol Evol 4, 937-953
   Abstract »    Full Text »    PDF »
i-ADHoRe 3.0--fast and sensitive detection of genomic homology in extremely large data sets.
S. Proost, J. Fostier, D. De Witte, B. Dhoedt, P. Demeester, Y. Van de Peer, and K. Vandepoele (2012)
Nucleic Acids Res. 40, e11
   Abstract »    Full Text »    PDF »
Evolutionary Changes of the Target Sites of Two MicroRNAs Encoded in the Hox Gene Cluster of Drosophila and Other Insect Species.
S. Miura, M. Nozawa, and M. Nei (2011)
Genome Biol Evol 3, 129-139
   Abstract »    Full Text »    PDF »
Morphology and behaviour: functional links in development and evolution.
R. C. Bertossa (2011)
Phil Trans R Soc B 366, 2056-2068
   Abstract »    Full Text »    PDF »
Epigenomic Reorganization of the Clustered Hox Genes in Embryonic Stem Cells Induced by Retinoic Acid.
V. Kashyap, L. J. Gudas, F. Brenet, P. Funk, A. Viale, and J. M. Scandura (2011)
J. Biol. Chem. 286, 3250-3260
   Abstract »    Full Text »    PDF »
Evolution of the Insect Yellow Gene Family.
L. C. Ferguson, J. Green, A. Surridge, and C. D. Jiggins (2011)
Mol. Biol. Evol. 28, 257-272
   Abstract »    Full Text »    PDF »
CpG island clusters and pro-epigenetic selection for CpGs in protein-coding exons of HOX and other transcription factors.
S. Branciamore, Z.-X. Chen, A. D. Riggs, and S. N. Rodin (2010)
PNAS 107, 15485-15490
   Abstract »    Full Text »    PDF »
Limited functions of Hox genes in the larval development of the ascidian Ciona intestinalis.
T. Ikuta, N. Satoh, and H. Saiga (2010)
Development 137, 1505-1513
   Abstract »    Full Text »    PDF »
Indirect development, transdifferentiation and the macroregulatory evolution of metazoans.
C. Arenas-Mena (2010)
Phil Trans R Soc B 365, 653-669
   Abstract »    Full Text »    PDF »
The Evolution of Gene Regulatory Interactions.
D. A. Garfield and G. A. Wray (2010)
BioScience 60, 15-23
   Abstract »    Full Text »    PDF »
How Did Indirect Development With Planktotrophic Larvae Evolve?.
C. Nielsen (2009)
Biol. Bull. 216, 203-215
   Abstract »    Full Text »    PDF »
Atypical relaxation of structural constraints in Hox gene clusters of the green anole lizard.
N. Di-Poi, J. I. Montoya-Burgos, and D. Duboule (2009)
Genome Res. 19, 602-610
   Abstract »    Full Text »    PDF »
A web-based software system for dynamic gene cluster comparison across multiple genomes.
K. V. Revanna, V. Krishnakumar, and Q. Dong (2009)
Bioinformatics 25, 956-957
   Abstract »    Full Text »    PDF »
A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster.
X. Zhang, Z. Lian, C. Padden, M. B. Gerstein, J. Rozowsky, M. Snyder, T. R. Gingeras, P. Kapranov, S. M. Weissman, and P. E. Newburger (2009)
Blood 113, 2526-2534
   Abstract »    Full Text »    PDF »
Adaptive Evolution of 5'HoxD Genes in the Origin and Diversification of the Cetacean Flipper.
Z. Wang, L. Yuan, S. J. Rossiter, X. Zuo, B. Ru, H. Zhong, N. Han, G. Jones, P. D. Jepson, and S. Zhang (2009)
Mol. Biol. Evol. 26, 613-622
   Abstract »    Full Text »    PDF »
Multigenome DNA sequence conservation identifies Hox cis-regulatory elements.
S. G. Kuntz, E. M. Schwarz, J. A. DeModena, T. De Buysscher, D. Trout, H. Shizuya, P. W. Sternberg, and B. J. Wold (2008)
Genome Res. 18, 1955-1968
   Abstract »    Full Text »    PDF »
Caudal, a key developmental regulator, is a DPE-specific transcriptional factor.
T. Juven-Gershon, J.-Y. Hsu, and J. T. Kadonaga (2008)
Genes & Dev. 22, 2823-2830
   Abstract »    Full Text »    PDF »
SNAREing the Basis of Multicellularity: Consequences of Protein Family Expansion during Evolution.
T. H. Kloepper, C. N. Kienle, and D. Fasshauer (2008)
Mol. Biol. Evol. 25, 2055-2068
   Abstract »    Full Text »    PDF »
Deciphering deuterostome phylogeny: molecular, morphological and palaeontological perspectives.
B. J Swalla and A. B Smith (2008)
Phil Trans R Soc B 363, 1557-1568
   Abstract »    Full Text »    PDF »
The Glucose Transporter (GLUT4) Enhancer Factor Is Required for Normal Wing Positioning in Drosophila.
U. Yazdani, Z. Huang, and J. R. Terman (2008)
Genetics 178, 919-929
   Abstract »    Full Text »    PDF »
Lsh controls Hox gene silencing during development.
S. Xi, H. Zhu, H. Xu, A. Schmidtmann, T. M. Geiman, and K. Muegge (2007)
PNAS 104, 14366-14371
   Abstract »    Full Text »    PDF »
The rise and fall of Hox gene clusters.
D. Duboule (2007)
Development 134, 2549-2560
   Abstract »    Full Text »    PDF »
Wnt signaling is a key mediator of Cdx1 expression in vivo.
N. Pilon, K. Oh, J.-R. Sylvestre, J. G. A. Savory, and D. Lohnes (2007)
Development 134, 2315-2323
   Abstract »    Full Text »    PDF »
Early Diversification of the TNF Superfamily in Teleosts: Genomic Characterization and Expression Analysis.
G. W. Glenney and G. D. Wiens (2007)
J. Immunol. 178, 7955-7973
   Abstract »    Full Text »    PDF »
A new paradigm for developmental biology.
J. S. Mattick (2007)
J. Exp. Biol. 210, 1526-1547
   Abstract »    Full Text »    PDF »

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