Analysis of Homologous Gene Clusters in Caenorhabditis elegans Reveals Striking Regional Cluster Domains

An algorithm for detecting local clusters of homologous genes was applied to the genome of Caenorhabditis elegans. Clusters of two or more homologous genes are abundant, totaling 1391 clusters containing 4607 genes, over one-fifth of all genes in C. elegans. Cluster genes are distributed unevenly in the genome, with the large majority located on autosomal chromosome arms, regions characterized by higher genetic recombination and more repeat sequences than autosomal centers and the X chromosome. Cluster genes are transcribed at much lower levels than average and very few have gross phenotypes as assayed by RNAi-mediated reduction of function. The molecular identity of cluster genes is unusual, with a preponderance of nematode-specific gene families that encode putative secreted and transmembrane proteins, and enrichment for genes implicated in xenobiotic detoxification and innate immunity. Gene clustering in Drosophila melanogaster is also substantial and the molecular identity of clustered genes follows a similar pattern. I hypothesize that autosomal chromosome arms in C. elegans undergo frequent local gene duplication and that these duplications support gene diversification and rapid evolution in response to environmental challenges. Although specific gene clusters have been documented in C. elegans, their abundance, genomic distribution, and unusual molecular identities were previously unrecognized.

[1]  J. Hoffmann,et al.  Activation of Drosophila Toll During Fungal Infection by a Blood Serine Protease , 2002, Science.

[2]  O. Gotoh,et al.  Divergent structures of Caenorhabditis elegans cytochrome P450 genes suggest the frequent loss and gain of introns during the evolution of nematodes. , 1998, Molecular biology and evolution.

[3]  D. Vaux,et al.  TRAF proteins and meprins share a conserved domain. , 1996, Trends in biochemical sciences.

[4]  I. Rodriguez,et al.  Sequence diversity and genomic organization of vomeronasal receptor genes in the mouse. , 2000, Genome research.

[5]  Bruce T Lahn,et al.  Adaptive evolution of MRG, a neuron-specific gene family implicated in nociception. , 2003, Genome research.

[6]  J. Berg Genome sequence of the nematode C. elegans: a platform for investigating biology. , 1998, Science.

[7]  M. Tyers,et al.  The BTB protein MEL-26 is a substrate-specific adaptor of the CUL-3 ubiquitin-ligase , 2003, Nature.

[8]  M. Akam Hox and HOM: Homologous gene clusters in insects and vertebrates , 1989, Cell.

[9]  J. Holton,et al.  Crystallographic analysis of CD40 recognition and signaling by human TRAF2. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[11]  S. Brunak,et al.  SHORT COMMUNICATION Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites , 1997 .

[12]  Ziheng Yang,et al.  PAML: a program package for phylogenetic analysis by maximum likelihood , 1997, Comput. Appl. Biosci..

[13]  Cori Bargmann,et al.  odr-10 Encodes a Seven Transmembrane Domain Olfactory Receptor Required for Responses to the Odorant Diacetyl , 1996, Cell.

[14]  E. Brown,et al.  Genomic analysis of gene expression in C. elegans. , 2000, Science.

[15]  J. Carlson,et al.  Molecular evolution of the insect chemoreceptor gene superfamily in Drosophila melanogaster , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Walter,et al.  Complete physical map of the human immunoglobulin heavy chain constant region gene complex. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Privé,et al.  The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R D Walter,et al.  Identification of stress-responsive genes in Caenorhabditis elegans using RT-PCR differential display. , 1998, Nucleic acids research.

[19]  Stephen J. Elledge,et al.  Insights into SCF ubiquitin ligases from the structure of the Skp1–Skp2 complex , 2000, Nature.

[20]  Gustavo Glusman,et al.  The complete human olfactory subgenome. , 2001, Genome research.

[21]  S. Ohno,et al.  Evolution from fish to mammals by gene duplication. , 2009, Hereditas.

[22]  T. Maniatis,et al.  Molecular cloning and characterization of the human β-like globin gene cluster , 1980, Cell.

[23]  Cori Bargmann,et al.  Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans , 1995, Cell.

[24]  Tim Schedl,et al.  fog-2 and the Evolution of Self-Fertile Hermaphroditism in Caenorhabditis , 2004, PLoS biology.

[25]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[26]  A. Sluder,et al.  The nuclear receptor superfamily has undergone extensive proliferation and diversification in nematodes. , 1999, Genome research.

[27]  T. Willson,et al.  Comparison of complete nuclear receptor sets from the human, Caenorhabditis elegans and Drosophila genomes , 2001, Genome Biology.

[28]  O. Terenius,et al.  Parasite‐specific immune response in adult Drosophila melanogaster: a genomic study , 2004, EMBO reports.

[29]  Zeynep F. Altun,et al.  Identification of a nematode chemosensory gene family. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[30]  C. Link,et al.  A stress-responsive glutathione S-transferase confers resistance to oxidative stress in Caenorhabditis elegans. , 2003, Free Radical Biology & Medicine.

[31]  A. Sluder,et al.  A C. elegans orphan nuclear receptor contributes to xenobiotic resistance , 2001, Current Biology.

[32]  S. Brunak,et al.  Improved prediction of signal peptides: SignalP 3.0. , 2004, Journal of molecular biology.

[33]  T. Maniatis,et al.  Molecular cloning and characterization of the human beta-like globin gene cluster. , 1980, Cell.

[34]  R. Leah,et al.  Biochemical and molecular characterization of three barley seed proteins with antifungal properties. , 1991, The Journal of biological chemistry.

[35]  M. Ashburner,et al.  Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila. , 1999, Science.

[36]  Y. Kohara,et al.  TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM , 2004, Nature Immunology.

[37]  Andrew Smith Genome sequence of the nematode C-elegans: A platform for investigating biology , 1998 .

[38]  T. Bogaert,et al.  A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible. , 2001, Archives of biochemistry and biophysics.

[39]  W. Swanson,et al.  A rapidly diverging EGF protein regulates species-specific signal transduction in early sea urchin development. , 2000, Developmental biology.

[40]  H. G. Boman,et al.  Antibacterial peptides: basic facts and emerging concepts , 2003, Journal of internal medicine.

[41]  Joanna L. Kelley,et al.  Adaptive evolution in the SRZ chemoreceptor families of Caenorhabditis elegans and Caenorhabditis briggsae. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[42]  X. Deng,et al.  Arabidopsis Has Two Redundant Cullin3 Proteins That Are Essential for Embryo Development and That Interact with RBX1 and BTB Proteins to Form Multisubunit E3 Ubiquitin Ligase Complexes in Vivow⃞ , 2005, The Plant Cell Online.

[43]  J. Barrett,et al.  A common class of nematode glutathione S-transferase (GST) revealed by the theoretical proteome of the model organism Caenorhabditis elegans. , 2001, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[44]  P. Zipperlen,et al.  Functional genomic analysis of C. elegans chromosome I by systematic RNA interference , 2000, Nature.

[45]  R. Treisman,et al.  The POZ domain: a conserved protein-protein interaction motif. , 1994, Genes & development.

[46]  S. Granjeaud,et al.  Inducible Antibacterial Defense System in C. elegans , 2002, Current Biology.

[47]  Jean Thierry-Mieg,et al.  A global analysis of Caenorhabditis elegans operons , 2002, Nature.

[48]  H. Robertson The large srh family of chemoreceptor genes in Caenorhabditis nematodes reveals processes of genome evolution involving large duplications and deletions and intron gains and losses. , 2000, Genome research.

[49]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[50]  E. Sonnhammer,et al.  Classification of transmembrane protein families in the Caenorhabditis elegans genome and identification of human orthologs. , 2000, Genome research.

[51]  M. Sunnerhagen,et al.  The new MATH: homology suggests shared binding surfaces in meprin tetramers and TRAF trimers , 2002, FEBS letters.

[52]  Y. Xiong,et al.  Targeting of protein ubiquitination by BTB–Cullin 3–Roc1 ubiquitin ligases , 2003, Nature Cell Biology.

[53]  Thomas Blumenthal,et al.  Coexpression of neighboring genes in Caenorhabditis elegans is mostly due to operons and duplicate genes. , 2003, Genome research.

[54]  Linda B. Buck,et al.  A family of candidate taste receptors in human and mouse , 2000, Nature.

[55]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[56]  K. Drickamer,et al.  C-Type lectin-like domains in Caenorhabditis elegans: predictions from the complete genome sequence. , 1999, Glycobiology.

[57]  H. Robertson Two large families of chemoreceptor genes in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae reveal extensive gene duplication, diversification, movement, and intron loss. , 1998, Genome research.

[58]  R. Durbin,et al.  The Genome Sequence of Caenorhabditis briggsae: A Platform for Comparative Genomics , 2003, PLoS biology.

[59]  H. Robertson Updating the str and srj (stl) families of chemoreceptors in Caenorhabditis nematodes reveals frequent gene movement within and between chromosomes. , 2001, Chemical senses.

[60]  Y. Kallberg,et al.  Short‐chain dehydrogenase/reductase (SDR) relationships: A large family with eight clusters common to human, animal, and plant genomes , 2002, Protein science : a publication of the Protein Society.

[61]  M. Lynch,et al.  The structure and early evolution of recently arisen gene duplicates in the Caenorhabditis elegans genome. , 2003, Genetics.

[62]  T. Aizawa,et al.  abf-1 and abf-2, ASABF-type antimicrobial peptide genes in Caenorhabditis elegans. , 2002, The Biochemical journal.

[63]  J. Thompson,et al.  The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. , 1997, Nucleic acids research.

[64]  T. Schedl,et al.  FOG-2, a novel F-box containing protein, associates with the GLD-1 RNA binding protein and directs male sex determination in the C. elegans hermaphrodite germline. , 2000, Development.

[65]  S. Elledge,et al.  BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3 , 2003, Nature.

[66]  C V Maina,et al.  Nuclear receptors in nematodes: themes and variations. , 2001, Trends in genetics : TIG.

[67]  Stephen J. Elledge,et al.  SKP1 Connects Cell Cycle Regulators to the Ubiquitin Proteolysis Machinery through a Novel Motif, the F-Box , 1996, Cell.

[68]  A. Coulson,et al.  Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis elegans. , 1995, Genetics.