Abstract
The genome of the nematode Caenorhabditis elegans was the first of any animal to be sequenced completely, and it remains the “gold standard” for completeness and annotations. Even before the C. elegans genome was completed, however, biologists began examining the generality of its features in the genomes of other Caenorhabditis species. With many such genomes now sequenced and available via WormBase, C. elegans researchers are often confronted with how to interpret comparative genomic data. In this article, we present practical approaches to addressing several common issues, including possible sources of error in homology annotations, the often complex relationships between sequence similarity, orthology, paralogy, and gene family evolution, the impact of sexual mode on genome assemblies and content, and the determination and use of synteny as a tool.
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References
The C. elegans Sequencing Consortium (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282:2012–2018
Colaiacovo MP, Stanfield GM, Reddy KC, Reinke V, Kim SK, Villeneuve AM (2002) A targeted RNAi screen for genes involved in chromosome morphogenesis and nuclear organization in the Caenorhabditis elegans germline. Genetics 162(1):113–128
Gonczy P, Echeverri C, Oegema K, Coulson A, Jones SJ, Copley RR, Duperon J, Oegema J, Brehm M, Cassin E, Hannak E, Kirkham M, Pichler S, Flohrs K, Goessen A, Leidel S, Alleaume AM, Martin C, Ozlu N, Bork P, Hyman AA (2000) Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature 408(6810):331–336
Simmer F, Moorman C, van der Linden AM, Kuijk E, van den Berghe PV, Kamath RS, Fraser AG, Ahringer J, Plasterk RH (2003) Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol 1(1), E12
Edgley M, D’Souza A, Moulder G, McKay S, Shen B, Gilchrist E, Moerman D, Barstead R (2002) Improved detection of small deletions in complex pools of DNA. Nucleic Acids Res 30(12), e52
Boulin T, Etchberger J, Hobert O (2006) Reporter gene fusions. In: WormBook, The C. elegans Research_Community, Editor 2006
Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dose AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska-Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM III, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, Ratsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH (2010) Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 330(6012):1775–1787
Reinke V, Gil IS, Ward S, Kazmer K (2004) Genome-wide germline-enriched and sex-biased expression profiles in Caenorhabditis elegans. Development 131(2):311–323
Kim SK, Lund J, Kiraly M, Duke K, Jiang M, Stuart JM, Eizinger A, Wylie BN, Davidson GS (2001) A gene expression map for Caenorhabditis elegans. Science 293(5537):2087–2092
Reinke V, Smith HE, Nance J, Wang J, Van Doren C, Begley R, Jones SJ, Davis EB, Scherer S, Ward S, Kim SK (2000) A global profile of germline gene expression in C. elegans. Mol Cell 6(3):605–616
Haag E, Pilgrim D (2005) Harnessing Caenorhabditis genomics for evolutionary developmental biology. Curr Genomics 6:579–588
Butler MH, Wall SM, Luehrsen KR, Fox GE, Hecht RM (1981) Molecular relationships between closely related strains and species of nematodes. J Mol Evol 18(1):18–23
Zucker-Aprison E, Blumenthal T (1989) Potential regulatory elements of nematode vitellogenin genes revealed by interspecies sequence comparison. J Mol Evol 28(6):487–496
Stein L et al (2003) The genome sequence of Caenorhabditis briggsae: a platform for comparative genomics. PLoS Biol 1:166–192
Lu ZJ, Yip KY, Wang G, Shou C, Hillier LW, Khurana E, Agarwal A, Auerbach R, Rozowsky J, Cheng C, Kato M, Miller DM, Slack F, Snyder M, Waterston RH, Reinke V, Gerstein MB (2011) Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data. Genome Res 21(2):276–285
Jovelin R, Cutter AD (2013) Fine-scale signatures of molecular evolution reconcile models of indel-associated mutation. Genome Biol Evol 5(5):978–986
Thomas CG, Li R, Smith HE, Woodruff GC, Oliver B, Haag ES (2012) Simplification and desexualization of gene expression in self-fertile nematodes. Curr Biol 22:2167–2172
Hillier LW, Miller RD, Baird SE, Chinwalla A, Fulton LA, Koboldt DC, Waterston RH (2007) Comparison of C. elegans and C. briggsae genome sequences reveals extensive conservation of chromosome organization and synteny. PLoS Biol 5(7), e167
Koboldt DC, Staisch J, Thillainathan B, Haines K, Baird SE, Chamberlin HM, Haag ES, Miller RD, Gupta BP (2010) A toolkit for rapid gene mapping in the nematode Caenorhabditis briggsae. BMC Genomics 11:236
Ross J, Koboldt D, Staisch J, Chamberlin H, Gupta BP, Milller R, Baird S, Haag E (2011) Caenorhabditis briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination. PLoS Genet 7(7), e1002174
Félix M-A, Braendle C, Cutter AD (2014) A streamlined system for species diagnosis in Caenorhabditis (Nematoda: Rhabditidae) with name designations for 15 distinct biological species. PLoS One 9(4), e94723
Dolgin ES, Charlesworth B, Baird SE, Cutter AD (2007) Inbreeding and outbreeding depression in Caenorhabditis nematodes. Evolution 61(6):1339–1352
Barriére A, Félix MA (2005) High local genetic diversity and low outcrossing rate in Caenorhabditis elegans natural populations. Curr Biol 15(13):1176–1184
Cutter AD, Felix MA, Barriere A, Charlesworth D (2006) Patterns of nucleotide polymorphism distinguish temperate and tropical wild isolates of Caenorhabditis briggsae. Genetics 173(4):2021–2031
Cutter AD, Baird SE, Charlesworth D (2006) High nucleotide polymorphism and rapid decay of linkage disequilibrium in wild populations of Caenorhabditis remanei. Genetics 174(2):901–913
Dey A, Chan CK, Thomas CG, Cutter AD (2013) Molecular hyperdiversity defines populations of the nematode Caenorhabditis brenneri. Proc Natl Acad Sci U S A 110(27):11056–11060
Barriere A, Wang S, Pekarek E, Thomas C, Haag E, Ruvinsky I (2009) Detecting heterozygosity in shotgun genome assemblies: lessons from obligately outcrossing nematodes. Genome Res 19:470–480
Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290(5494):1151–1155
Huang S, Chen Z, Huang G, Yu T, Yang P, Li J, Fu Y, Yuan S, Chen S, Xu A (2012) HaploMerger: reconstructing allelic relationships for polymorphic diploid genome assemblies. Genome Res 22(8):1581–1588
Cutter AD (2008) Reproductive evolution: symptom of a selfing syndrome. Curr Biol 18(22):R1056–R1058
Thomas CG, Woodruff GC, Haag ES (2012) Causes and consequences of the evolution of reproductive mode in Caenorhabditis nematodes. Trends Genet 28(5):213–220
Wang J, Chen PJ, Wang GJ, Keller L (2010) Chromosome size differences may affect meiosis and genome size. Science 329(5989):293
Ostlund G, Schmitt T, Forslund K, Kostler T, Messina DN, Roopra S, Frings O, Sonnhammer EL (2010) InParanoid 7: new algorithms and tools for eukaryotic orthology analysis. Nucleic Acids Res 38(Database issue):D196–D203
Nayak S, Goree J, Schedl T (2005) fog-2 and the evolution of self-fertile hermaphroditism in Caenorhabditis. PLoS Biol 3, e6
Altenhoff A, Dessimoz C (2012) Chpt. 9: Inferring orthology and paralogy. In: Anisimova M (ed) Evolutionary genomics, statistical and computational methods, vol 1. Humana Press, New York, pp 259–279
Li H, Coghlan A, Ruan J, Coin LJ, Heriche JK, Osmotherly L, Li R, Liu T, Zhang Z, Bolund L, Wong GK, Zheng W, Dehal P, Wang J, Durbin R (2006) TreeFam: a curated database of phylogenetic trees of animal gene families. Nucleic Acids Res 34(Database issue):D572–D580
Li L, Stoeckert CJ Jr, Roos DS (2003) OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res 13(9):2178–2189
Lamont LB, Crittenden SL, Bernstein D, Wickens M, Kimble J (2004) FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline. Dev Cell 7(5):697–707
Liu Q, Stumpf C, Wickens M, Haag ES (2012) Context-dependent function of a conserved translational regulatory module. Development 139:1509–1521
Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402
Zhang T, Sun Y, Tian E, Deng H, Zhang Y, Luo X, Cai Q, Wang H, Chai J, Zhang H (2006) RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex in C. elegans. Development 133(6):1023–1033
Kuwabara PE, Shah S (1994) Cloning by synteny: identifying C. briggsae homologues of C. elegans genes. Nucleic Acids Res 22:4414–4418
Haag ES, Ackerman AD (2005) Intraspecific variation in fem-3 and tra-2, two rapidly coevolving nematode sex-determining genes. Gene 349:35–42
Rockman MV, Kruglyak L (2009) Recombinational landscape and population genomics of Caenorhabditis elegans. PLoS Genet 5(3), e1000419
Thomas JH, Kelley JL, Robertson HM, Ly K, Swanson WJ (2005) Adaptive evolution in the SRZ chemoreceptor families of Caenorhabditis elegans and Caenorhabditis briggsae. Proc Natl Acad Sci U S A 102(12):4476–4481
Swofford D, Olsen G, Waddell P, Hillis D (1996) Chpt. 11: Phylogenetic inference. In: Hillis D, Moritz C, Mable B (eds) Molecular systematics. Sinauer Associates, Sunderland, MA
Whelan S (2008) Inferring trees. In: Keith J (ed) Bioinformatics, vol 1, Data, sequence analysis, and evolution. Humana Press, Totowa, NJ, pp 287–309
Cutter AD, Dey A, Murray RL (2009) Evolution of the Caenorhabditis elegans genome. Mol Biol Evol 26(6):1199–1234
Haag ES, Wang S, Kimble J (2002) Rapid coevolution of the nematode sex-determining genes fem-3 and tra-2. Curr Biol 12(23):2035–2041
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215(3):403–410
Eddy S (2001) HMMER: profile hidden Markov models for biological sequence analysis., Available from: http://hmmer.wustl.edu
Finn RD, Clements J, Eddy SR (2011) HMMER web server: interactive sequence similarity searching. Nucleic Acids Res 39(Web Server issue):W29–W37
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Haag, E.S., Thomas, C.G. (2015). Fundamentals of Comparative Genome Analysis in Caenorhabditis Nematodes. In: Biron, D., Haspel, G. (eds) C. elegans. Methods in Molecular Biology, vol 1327. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4939-2842-2_2
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DOI: https://doi.org/10.1007/978-1-4939-2842-2_2
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