View More View Less
  • 1 Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of Malaria Research, Dwarka, New Delhi, India
  • | 2 Department of Biotechnology, Kumaun University, Nainital, Uttarakhand, India
  • | 3 Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of Malaria Research, Sector-8, Dwarka, New Delhi, 110077, India
Restricted access

Abstract

Aim

The present-day genetic architecture of a species bears much significance to its closely related species. In recent availability of whole genome sequence data for closely related species, it is possible to detect genetic similarities/differences in specific lineages and infer the role of evolutionary forces in bringing such similarities/differences. In this respect, NAT2 gene, responsible for drug metabolism, is conserved across a few taxa and, thus, comparative genomic studies could be useful for better pharmacogenetic realization.

Methods

DNA sequences of human NAT2 gene were retrieved from NCBI and characterized. Comparative and evolutionary analyses were performed with sequences from four mammalian taxa and one avian taxon with different statistical algorithms.

Results

The observed genetic architecture of NAT2 gene was different across the taxa. Phylogenetic inferences revealed that human and chimpanzee are diverged recently and fowl was found to be diverged from rest of the taxa significantly. Also, gene length, microsatellites, Ka/Ks, secondary structure, and distribution of CpG islands were observed across taxa.

Conclusions

The detail architecture of NAT2 gene and its evolutionary history in different taxa show relationships with other taxa. Future population-based study in NAT2 would unravel the correlation between nucleotide changes and differential ability of drug metabolization in humans.

  • 1. A. Das M. Sharma B. Gupta A.P. Dash 2009 Plasmodium falciparum and Plasmodium vivax: so similar, yet very different Parasitol Res 105 1169 1171.

    • Search Google Scholar
    • Export Citation
  • 2. G. Awasthi A.P. Dash A. Das 2009 Evolutionary insights into Duffy gene in mammalian taxa with comparative genetic analyses J Vector Borne Dis 46 230 236.

    • Search Google Scholar
    • Export Citation
  • 3. K. Tamura J. Dudley M. Nei S. Kumar 2007 MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0 Mol Biol Evol 24 1596 1599.

    • Search Google Scholar
    • Export Citation
  • 4. M.D. Niculescu S.H. Zeisel 2002 Diet, methyl donors and DNA methylation: interactions between dietary folate, methionine and choline J Nutr 132 2333S 2335S.

    • Search Google Scholar
    • Export Citation
  • 5. A.K. Daly 2003 Pharmacogenetics of the major polymorphic metabolizing enzymes Fundam Clin Pharmacol 17 27 41.

  • 6. B. Chen W.X. Zhag W.X. Cai 2006 The influence of various genotypes on the metabolic activity of NAT2 in a Chinese population Eur J Clin Pharmacol 62 355 359.

    • Search Google Scholar
    • Export Citation
  • 7. D.W. Hein S. Boukouvala D.M. Grant R.F. Minchind E. Sim 2008 Changes in consensus arylamine N-acetyltransferase (NAT) gene nomenclature Pharmacogenet Genom 18 367 368.

    • Search Google Scholar
    • Export Citation
  • 8. F. Luca G. Bubba M. Basile R. Brdicka E. Michalodimitrakis O. Richards et al. 2008 Multiple advantageous amino acid variants in the NAT2 gene in human populations PLoS One 3 e3136.

    • Search Google Scholar
    • Export Citation
  • 9. S. Boukouvala E. Sim 2005 Structural analysis of the genes for human arylamine N-acetyltransferases and characterization of alternative transcripts Basic Clin Pharmacol Toxicol 96 343 351.

    • Search Google Scholar
    • Export Citation
  • 10. S. Fuselli R.H. Gilman S.J. Chanock S.L. Bonatto G. De Stefano C.A. Evans et al. 2007 Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across native American populations and high intra-population diversity Pharmacogenomics J 7 144 152.

    • Search Google Scholar
    • Export Citation
  • 11. R. Moslehi N. Chatterjee T.R. Church M. Yeager D.W. Hein R.B. Hayes 2007 Cigarette smoking, N-acetyltransferase genes and the risk of advanced colorectal adenoma Pharmacogenomics 7 819 829.

    • Search Google Scholar
    • Export Citation
  • 12. J. Rozas J.C. Sanchez-DelBarrio X. Messeguer R. Rozas 2003 DnaSP, DNA polymorphism analyses by the coalescent and other methods Bioinformatics 19 2496 2497.

    • Search Google Scholar
    • Export Citation
  • 13. P.R.R. Totino C.T.D. Ribeiro M.D.F. Ferreira-da-Cruz 2009 Pro-apoptotic effects of antimalarial drugs do not affect mature human erythrocytes Acta Trop 112 236 238.

    • Search Google Scholar
    • Export Citation
  • 14. S.B. Mudunuri H.A. Nagarajaram 2007 IMEx: Imperfect Microsatellite Extractor Bioinformatics 23 1181 1187.

  • 15. E. Patin C. Harmant K.K. Kidd J. Kidd A. Froment S.Q. Mehdi et al. 2006 Sub-Saharan African coding sequence variation and haplotype diversity at the NAT2 gene Hum Mutat 27 720 731.

    • Search Google Scholar
    • Export Citation
  • 16. T.J. Sharpton D.E. Neafsey J.E. Galagan J.W. Taylor 2008 Mechanisms of intron gain and loss in Cryptococcus Genome Biol 9 R24.

  • 17. CpG Island searcher programme [http://ebi.ac.uk/tools/emboss/CpGplot.html].

  • 18. M. Gardiner-Garden M. Frommer 1987 CpG islands in vertebrate genomes J Mol Biol 196 261 282.

  • 19. Pearson's correlation coefficient [http://analyse-it.com].

  • 20. Microsatellite finder [http://www.cdfd.org.in/imex].

  • 21. Protein secondary structure [http:www.ibcp.fr].

  • 22. W.T. Hughes 1998 Use of Dapsone in the prevention and treatment of Pneumocystis Carinii Pneumonia: a review Clin Infect Dis 27 191 204.

    • Search Google Scholar
    • Export Citation
  • 23. A. Sabbagh P. Darlu 2005 Inferring haplotypes at the NAT2 locus: the computational approach BMC Genet 6 30.

  • 24. J.C. Niles J.L. Derisi M.A. Marletta 2009 Inhibiting Plasmodium falciparum growth and heme detoxification pathway using heme-binding DNA aptamers Proc Natl Acad Sci USA 106 13266 13271.

    • Search Google Scholar
    • Export Citation
  • 25. S. Asthana W.S. Noble G. Kryukov C.E. Grant S. Sunyaev 2007 Stamatoyannopoulos JA: Wide distributed non-coding purifying selection in the human genome Proc Natl Acad Sci USA 104 12410 12415.

    • Search Google Scholar
    • Export Citation
  • 26. L. Duret 2001 Why do genes have introns? Recombination might add a new piece to the puzzle Trends Genet 17 172 175.

  • 27. L. Carmel I.B. Rogozin Y.I. Wolf 2007 Evolutionarily conserved genes preferentially accumulate introns Genome Res 17 1045 1050.

  • 28. G. Awasthi S. Singh A.P. Dash A. Das 2008 Genetic characterization and evolutionary inferences of TNF-α through computational analysis Braz J Infect Dis 12 374 379.

    • Search Google Scholar
    • Export Citation
  • 29. G. Awasthi A.P. Dash A. Das 2009 Characterization and evolutionary analysis of human CD36 gene Indian J Med Res 129 534 541.

  • 30. A. Sekine S. Saito A. Iida Y. Mitsunobu S. Higuchi S. Harigae et al. 2001 Identification of single-nucleotide polymorphisms (SNPs) of human N-acetyltransferase genes NAT1, NAT2, AANAT, ARD1 and L1CAM in the Japanese population J Hum Genet 46 314 319.

    • Search Google Scholar
    • Export Citation
  • 31. S.K. Shakyawar B.K. Joshi D. Kumar 2009 SSR repeat dynamics in mitochondrial genomes of five domestic animal species Bioinformation 4 158 163.

    • Search Google Scholar
    • Export Citation
  • 32. G. Strathdee A. Simand R. Brown 2004 Control of gene expression by CpG island methylation in normal cells Biochem Soc Trans 32 913 915.

    • Search Google Scholar
    • Export Citation
  • 33. G.I. Bell J. Jurka 1997 The length distribution of perfect dimer repetitive DNA is consistent with its evolution by an unbiased single-step mutation process J Mol Evol 44 414 421.

    • Search Google Scholar
    • Export Citation
  • 34. Y.C. Li A.B. Korol T. Fahima E. Nevo 2004 Microsatellites within genes: structure, function, and evolution Mol Biol Evol 21 991 1007.

    • Search Google Scholar
    • Export Citation
  • 35. T. Satoh 2007 Genetic polymorphism in drug metabolism and toxicity: linking animal research and risk assessment in man AATEX 14 443 445.

    • Search Google Scholar
    • Export Citation
  • 36. G. Toth Z. Gaspari J. Jurka 2000 Microsatellites in different eukaryotic genomes: survey and analysis Genome Res 10 967 981.

  • 37. C. Bock J. Walter M. Paulsen T. Lengauer 2007 CpG island mapping by epigenome prediction PLOS Comp Biol 3 e110.

  • 38. L. Han Z. Zhao 2008 Comparative analysis of CpG islands in four fish genomes Comp Funct Genomics 2008 6.

  • 39. M. Sharma A.P. Dash A. Das 2010 Evolutionary genetic insights into Plasmodium falciparum functional genes Parasitol Res 106 349 355.

    • Search Google Scholar
    • Export Citation
  • 40. C.L. Ulrey L. Liu L.G. Andrews T.O. Tollefsbol 2005 The impact of meta bolism on DNA methylation Hum Mol Genet 14 R139 R147.

  • 41. S. Bekaert S. Storozhenko P. Mehrshahi M.J. Bennett W. Lambert J.F. Gregory et al. 2007 Folate biofortification in food plants Trends Plant Sci 13 28 35.

    • Search Google Scholar
    • Export Citation
  • 43. J.Y. Fang S.D. Xiao 2003 Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis J Gastroenterol 38 821 829.

    • Search Google Scholar
    • Export Citation
  • 44. W. Messier C.B. Stewart 1997 Episodic adaptive evolution of primate lysozymes Nature 385 151 154.

  • 45. S.E. Lindstrom Y. Hiromoto H. Nishimura T. Saito R. Nerome K. Nerome 1999 Comparative analysis of evolutionary mechanisms of the hemagglutinin and three internal protein genes of influenza B virus: multiple cocirculating lineages and frequent reassortment of the NP, M, and NS genes J Virol 73 4413 4426.

    • Search Google Scholar
    • Export Citation
  • 46. S.E. Massey G. Moura P. Beltrao R. Almeida J.R. Garey M.F. Tuite et al. 2003 Comparative evolutionary genomics unveils the molecular mechanism of reassignment of the CTG codon in Candida spp Genome Res 13 544 557.

    • Search Google Scholar
    • Export Citation
  • 47. J.K. Inflow L.L. Restifo 2004 Molecular and evolutionary genetics of mental retardation Genetics 166 835 846.

  • 48. E. Vagena G. Fakis S. Boukouvala 2008 Arylamine N-acetyltransferases in prokaryotic and eukaryotic genomes: a survey of public databases Curr Drug Metabol 9 628 660.

    • Search Google Scholar
    • Export Citation
  • 49. L. Wakefield S. Boukouvala E. Sim 2010 Characterisation of CpG methylation in the upstream control region of mouse Nat2: evidence for a gene-environment interaction in a polymorphic gene implicated in folate metabolism Gene 452 16 21.

    • Search Google Scholar
    • Export Citation
  • 50. K.F. Windmill A. Gaedigk P.D. Hall H. Samaratunga D.M. Grant M.E. McManus 2000 Localization of N-acetyltransferases NAT1 and NAT2 in human tissues Toxicol Sci 54 19 29.

    • Search Google Scholar
    • Export Citation
  • 51. H. Wu L. Dombrovsky W. Tempel F. Martin P. Loppnau G.H. Goodfellow et al. 2007 Structural basis of substrate-binding specificity of human arylamine N-acetyltranferases J Biol Chem 282 30189 30197.

    • Search Google Scholar
    • Export Citation

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jan 2021 11 0 0
Feb 2021 0 0 0
Mar 2021 0 0 0
Apr 2021 0 0 0
May 2021 2 0 0
Jun 2021 0 0 0
Jul 2021 0 0 0