-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
Duplication and Retention Biases of Essential and Non-Essential Genes Revealed by Systematic Knockdown Analyses
: When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog. This is supported by indirect evidence showing that multi-copy genes show loss-of-function phenotypes less often than single-copy genes and by direct tests of phenotype masking using select gene sets. Here we take a systematic genome-wide RNA interference approach to assess phenotype masking in paralog pairs in the Caenorhabditis elegans genome. Remarkably, in contrast to expectations, we find that phenotype masking makes only a minor contribution to the low knockdown phenotype rate for duplicate genes. Instead, we find that non-essential genes are highly over-represented among duplicates, leading to a low observed loss-of-function phenotype rate. We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods. We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.
Vyšlo v časopise: Duplication and Retention Biases of Essential and Non-Essential Genes Revealed by Systematic Knockdown Analyses. PLoS Genet 9(5): e32767. doi:10.1371/journal.pgen.1003330
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003330Souhrn
: When a duplicate gene has no apparent loss-of-function phenotype, it is commonly considered that the phenotype has been masked as a result of functional redundancy with the remaining paralog. This is supported by indirect evidence showing that multi-copy genes show loss-of-function phenotypes less often than single-copy genes and by direct tests of phenotype masking using select gene sets. Here we take a systematic genome-wide RNA interference approach to assess phenotype masking in paralog pairs in the Caenorhabditis elegans genome. Remarkably, in contrast to expectations, we find that phenotype masking makes only a minor contribution to the low knockdown phenotype rate for duplicate genes. Instead, we find that non-essential genes are highly over-represented among duplicates, leading to a low observed loss-of-function phenotype rate. We further find that duplicate pairs derived from essential and non-essential genes have contrasting evolutionary dynamics: whereas non-essential genes are both more often successfully duplicated (fixed) and lost, essential genes are less often duplicated but upon successful duplication are maintained over longer periods. We expect the fundamental evolutionary duplication dynamics presented here to be broadly applicable.
Zdroje
1. ConantGC, WolfeKH (2008) Turning a hobby into a job: how duplicated genes find new functions. Nat Rev Genet 9 : 938–950.
2. Ohno S (1970) Evolution by gene duplication. New York: Springer-Verlag.
3. CookeJ, NowakMA, BoerlijstM, Maynard-SmithJ (1997) Evolutionary origins and maintenance of redundant gene expression during metazoan development. Trends Genet 13 : 360–364.
4. Haldane J (1932) The causes of evolution. New York: Longmans, Green & Co., and New York: Harper Brothers.
5. KirschnerM, GerhartJ (1998) Evolvability. Proc Natl Acad Sci U S A 95 : 8420–8427.
6. NowakMA, BoerlijstMC, CookeJ, SmithJM (1997) Evolution of genetic redundancy. Nature 388 : 167–171.
7. TautzD (1992) Redundancies, development and the flow of information. Bioessays 14 : 263–266.
8. ThomasJH (1993) Thinking about genetic redundancy. Trends Genet 9 : 395–399.
9. WilkinsAS (1997) Canalization: a molecular genetic perspective. Bioessays 19 : 257–262.
10. ClarkAG (1994) Invasion and maintenance of a gene duplication. Proc Natl Acad Sci U S A 91 : 2950–2954.
11. KamathRS, FraserAG, DongY, PoulinG, DurbinR, et al. (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421 : 231–237.
12. ChenWH, TrachanaK, LercherMJ, BorkP (2012) Younger genes are less likely to be essential than older genes, and duplicates are less likely to be essential than singletons of the same age. Mol Biol Evol 29 : 1703–1706.
13. ConantGC, WagnerA (2004) Duplicate genes and robustness to transient gene knock-downs in Caenorhabditis elegans. Proc Biol Sci 271 : 89–96.
14. GuZ, SteinmetzLM, GuX, ScharfeC, DavisRW, et al. (2003) Role of duplicate genes in genetic robustness against null mutations. Nature 421 : 63–66.
15. MakinoT, HokampK, McLysaghtA (2009) The complex relationship of gene duplication and essentiality. Trends Genet
16. SuZ, GuX (2008) Predicting the Proportion of Essential Genes in Mouse Duplicates Based on Biased Mouse Knockout Genes. J Mol Evol
17. HeX, ZhangJ (2006) Higher duplicability of less important genes in yeast genomes. Mol Biol Evol 23 : 144–151.
18. DeanEJ, DavisJC, DavisRW, PetrovDA (2008) Pervasive and persistent redundancy among duplicated genes in yeast. PLoS Genet 4: e1000113 doi:10.1371/journal.pgen.1000113.
19. DeLunaA, VetsigianK, ShoreshN, HegrenessM, Colon-GonzalezM, et al. (2008) Exposing the fitness contribution of duplicated genes. Nat Genet 40 : 676–681.
20. IhmelsJ, CollinsSR, SchuldinerM, KroganNJ, WeissmanJS (2007) Backup without redundancy: genetic interactions reveal the cost of duplicate gene loss. Mol Syst Biol 3 : 86.
21. MussoG, CostanzoM, HuangfuM, SmithAM, PawJ, et al. (2008) The extensive and condition-dependent nature of epistasis among whole-genome duplicates in yeast. Genome Res 18 : 1092–1099.
22. TischlerJ, LehnerB, ChenN, FraserAG (2006) Combinatorial RNA interference in Caenorhabditis elegans reveals that redundancy between gene duplicates can be maintained for more than 80 million years of evolution. Genome Biol 7: R69.
23. HartmanJLt, GarvikB, HartwellL (2001) Principles for the buffering of genetic variation. Science 291 : 1001–1004.
24. LiJ, YuanZ, ZhangZ (2010) The cellular robustness by genetic redundancy in budding yeast. PLoS Genet 6: e1001187 doi:10.1371/journal.pgen.1001187.
25. SieburthD, Ch'ngQ, DybbsM, TavazoieM, KennedyS, et al. (2005) Systematic analysis of genes required for synapse structure and function. Nature 436 : 510–517.
26. WangD, KennedyS, ConteDJr, KimJK, GabelHW, et al. (2005) Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants. Nature 436 : 593–597.
27. KennedyS, WangD, RuvkunG (2004) A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427 : 645–649.
28. FraserAG, KamathRS, ZipperlenP, Martinez-CamposM, SohrmannM, et al. (2000) Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408 : 325–330.
29. SimmerF, MoormanC, van der LindenAM, KuijkE, van den BerghePV, et al. (2003) Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol 1: e12 doi:10.1371/journal.pbio.0000012.
30. RualJF, CeronJ, KorethJ, HaoT, NicotAS, et al. (2004) Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Res 14 : 2162–2168.
31. VanderSluisB, BellayJ, MussoG, CostanzoM, PappB, et al. (2010) Genetic interactions reveal the evolutionary trajectories of duplicate genes. Mol Syst Biol 6 : 429.
32. CutterAD (2008) Divergence times in Caenorhabditis and Drosophila inferred from direct estimates of the neutral mutation rate. Mol Biol Evol 25 : 778–786.
33. ShayeDD, GreenwaldI (2011) OrthoList: a compendium of C. elegans genes with human orthologs. PLoS ONE 6: e20085 doi:10.1371/journal.pone.0020085.
34. LynchM, ConeryJS (2000) The evolutionary fate and consequences of duplicate genes. Science 290 : 1151–1155.
35. Lynch M (2004) Gene duplication and evolution; Font AMaE, editor. New York: Oxford University Press. p.
36. HurstLD, SmithNG (1999) Do essential genes evolve slowly? Curr Biol 9 : 747–750.
37. KrylovDM, WolfYI, RogozinIB, KooninEV (2003) Gene loss, protein sequence divergence, gene dispensability, expression level, and interactivity are correlated in eukaryotic evolution. Genome Res 13 : 2229–2235.
38. PalC, PappB, HurstLD (2001) Highly expressed genes in yeast evolve slowly. Genetics 158 : 927–931.
39. NguyenDQ, WebberC, Hehir-KwaJ, PfundtR, VeltmanJ, et al. (2008) Reduced purifying selection prevails over positive selection in human copy number variant evolution. Genome Res 18 : 1711–1723.
40. DopmanEB, HartlDL (2007) A portrait of copy-number polymorphism in Drosophila melanogaster. Proc Natl Acad Sci U S A 104 : 19920–19925.
41. RedonR, IshikawaS, FitchKR, FeukL, PerryGH, et al. (2006) Global variation in copy number in the human genome. Nature 444 : 444–454.
42. LindsaySJ, KhajaviM, LupskiJR, HurlesME (2006) A chromosomal rearrangement hotspot can be identified from population genetic variation and is coincident with a hotspot for allelic recombination. Am J Hum Genet 79 : 890–902.
43. BarnesTM, KoharaY, CoulsonA, HekimiS (1995) Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis elegans. Genetics 141 : 159–179.
44. RockmanMV, KruglyakL (2009) Recombinational landscape and population genomics of Caenorhabditis elegans. PLoS Genet 5: e1000419 doi:10.1371/journal.pgen.1000419.
45. consortium Ces (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282 : 2012–2018.
46. LiangH, LiWH (2007) Gene essentiality, gene duplicability and protein connectivity in human and mouse. Trends Genet 23 : 375–378.
47. PappB, PalC, HurstLD (2003) Dosage sensitivity and the evolution of gene families in yeast. Nature 424 : 194–197.
48. AltschulSF, GishW, MillerW, MyersEW, LipmanDJ (1990) Basic local alignment search tool. J Mol Biol 215 : 403–410.
49. EnrightAJ, Van DongenS, OuzounisCA (2002) An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res 30 : 1575–1584.
50. BaughLR, WenJC, HillAA, SlonimDK, BrownEL, et al. (2005) Synthetic lethal analysis of Caenorhabditis elegans posterior embryonic patterning genes identifies conserved genetic interactions. Genome Biol 6: R45.
51. ZipperlenP, FraserAG, KamathRS, Martinez-CamposM, AhringerJ (2001) Roles for 147 embryonic lethal genes on C.elegans chromosome I identified by RNA interference and video microscopy. Embo J 20 : 3984–3992.
52. LiH, CoghlanA, RuanJ, CoinLJ, HericheJK, et al. (2006) TreeFam: a curated database of phylogenetic trees of animal gene families. Nucleic Acids Res 34: D572–580.
53. StormCE, SonnhammerEL (2002) Automated ortholog inference from phylogenetic trees and calculation of orthology reliability. Bioinformatics 18 : 92–99.
54. ZmasekCM, EddySR (2002) RIO: analyzing proteomes by automated phylogenomics using resampled inference of orthologs. BMC Bioinformatics 3 : 14.
55. FlicekP, AmodeMR, BarrellD, BealK, BrentS, et al. Ensembl 2012. Nucleic Acids Res 40: D84–90.
56. LiWH (1993) Unbiased estimation of the rates of synonymous and nonsynonymous substitution. J Mol Evol 36 : 96–99.
57. Nei M, Kumar S (2000) Molecular evolution and phylogenetics. New York: Oxford University Press.
58. BauerS, GrossmannS, VingronM, RobinsonPN (2008) Ontologizer 2.0–a multifunctional tool for GO term enrichment analysis and data exploration. Bioinformatics 24 : 1650–1651.
59. LiuT, RechtsteinerA, EgelhoferTA, VielleA, LatorreI, et al. (2011) Broad chromosomal domains of histone modification patterns in C. elegans. Genome Res 21 : 227–236.
60. HillierLW, ReinkeV, GreenP, HirstM, MarraMA, et al. (2009) Massively parallel sequencing of the polyadenylated transcriptome of C. elegans. Genome Res 19 : 657–666.
Štítky
Genetika Reprodukčná medicína
Článek Attachment Site Selection and Identity in Bxb1 Serine Integrase-Mediated Site-Specific RecombinationČlánek Bck2 Acts through the MADS Box Protein Mcm1 to Activate Cell-Cycle-Regulated Genes in Budding YeastČlánek High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple IsolatesČlánek Neuropeptides Function in a Homeostatic Manner to Modulate Excitation-Inhibition Imbalance inČlánek Implicates Tyrosine-Sulfated Peptide Signaling in Susceptibility and Resistance to Root Infection
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2013 Číslo 5- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- Functional Elements Are Embedded in Structurally Constrained Sequences
- RNA–Mediated Epigenetic Heredity Requires the Cytosine Methyltransferase Dnmt2
- Loss of Expression and Promoter Methylation of SLIT2 Are Associated with Sessile Serrated Adenoma Formation
- Attachment Site Selection and Identity in Bxb1 Serine Integrase-Mediated Site-Specific Recombination
- Human Genetics in Rheumatoid Arthritis Guides a High-Throughput Drug Screen of the CD40 Signaling Pathway
- Genome-Wide Analysis in German Shepherd Dogs Reveals Association of a Locus on CFA 27 with Atopic Dermatitis
- Liver X Receptors Protect from Development of Prostatic Intra-Epithelial Neoplasia in Mice
- Chromosomal Organization and Segregation in
- A Statistical Framework for Joint eQTL Analysis in Multiple Tissues
- Cell Polarity and Patterning by PIN Trafficking through Early Endosomal Compartments in
- Bck2 Acts through the MADS Box Protein Mcm1 to Activate Cell-Cycle-Regulated Genes in Budding Yeast
- High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Isolates
- Neuropeptides Function in a Homeostatic Manner to Modulate Excitation-Inhibition Imbalance in
- A Compendium of Nucleosome and Transcript Profiles Reveals Determinants of Chromatin Architecture and Transcription
- Wnt Signaling Regulates the Lineage Differentiation Potential of Mouse Embryonic Stem Cells through Tcf3 Down-Regulation
- Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Spermatheca
- The Specificity and Flexibility of L1 Reverse Transcription Priming at Imperfect T-Tracts
- Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations
- Implicates Tyrosine-Sulfated Peptide Signaling in Susceptibility and Resistance to Root Infection
- Clathrin and AP2 Are Required for Phagocytic Receptor-Mediated Apoptotic Cell Clearance in
- Encodes CDF Transporters That Excrete Zinc from Intestinal Cells of and Act in a Parallel Negative Feedback Circuit That Promotes Homeostasis
- Global Properties and Functional Complexity of Human Gene Regulatory Variation
- DNA Binding of the Cell Cycle Transcriptional Regulator GcrA Depends on N6-Adenosine Methylation in and Other
- Side Effects: Substantial Non-Neutral Evolution Flanking Regulatory Sites
- From Paramutation to Paradigm
- From Mouse to Human: Evolutionary Genomics Analysis of Human Orthologs of Essential Genes
- Distinct Translational Control in CD4 T Cell Subsets
- Female Bias in and Regulation by the Histone Demethylase KDM6A
- ATM–Dependent MiR-335 Targets CtIP and Modulates the DNA Damage Response
- HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages
- The Majority of Primate-Specific Regulatory Sequences Are Derived from Transposable Elements
- Identification of Meiotic Cyclins Reveals Functional Diversification among Plant Cyclin Genes
- EGL-13/SoxD Specifies Distinct O and CO Sensory Neuron Fates in
- Congruence of Additive and Non-Additive Effects on Gene Expression Estimated from Pedigree and SNP Data
- Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits
- Ikbkap/Elp1 Deficiency Causes Male Infertility by Disrupting Meiotic Progression
- Analysis of the Genetic Basis of Disease in the Context of Worldwide Human Relationships and Migration
- Duplication and Retention Biases of Essential and Non-Essential Genes Revealed by Systematic Knockdown Analyses
- Strong Purifying Selection at Synonymous Sites in
- , a Susceptibility Gene for Type 1 and Type 2 Diabetes, Modulates Pancreatic Beta Cell Apoptosis via Regulation of a Splice Variant of the BH3-Only Protein
- Chromosome Movements Promoted by the Mitochondrial Protein SPD-3 Are Required for Homology Search during Meiosis
- The Secretory Pathway Calcium ATPase PMR-1/SPCA1 Has Essential Roles in Cell Migration during Embryonic Development
- The Genomic Signature of Crop-Wild Introgression in Maize
- CDK4 T172 Phosphorylation Is Central in a CDK7-Dependent Bidirectional CDK4/CDK2 Interplay Mediated by p21 Phosphorylation at the Restriction Point
- Genome-Wide Identification of Regulatory RNAs in the Human Pathogen
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits
- HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages
- Female Bias in and Regulation by the Histone Demethylase KDM6A
- ATM–Dependent MiR-335 Targets CtIP and Modulates the DNA Damage Response
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy