Duplicated Paralogous Genes Subject to Positive Selection in the Genome of Trypanosoma brucei

Background Whole genome studies have highlighted duplicated genes as important substrates for adaptive evolution. We have investigated adaptive evolution in this class of genes in the human parasite Trypanosoma brucei, as indicated by the ratio of non-synonymous (amino-acid changing) to synonymous (amino acid retaining) nucleotide substitution rates. Methodology/Principal Findings We have identified duplicated genes that are most rapidly evolving in this important human parasite. This is the first attempt to investigate adaptive evolution in this species at the codon level. We identify 109 genes within 23 clusters of paralogous gene expansions to be subject to positive selection. Conclusions/Significance Genes identified include surface antigens in both the mammalian and insect host life cycle stage suggesting that competitive interaction is not solely with the adaptive immune system of the mammalian host. Also surface transporters related to drug resistance and genes related to developmental progression are detected. We discuss how adaptive evolution of these genes may highlight lineage specific processes essential for parasite survival. We also discuss the implications of adaptive evolution of these targets for parasite biology and control.

[1]  K. Crandall,et al.  The causes and consequences of HIV evolution , 2004, Nature Reviews Genetics.

[2]  Richard D Emes,et al.  Comparison of the genomes of human and mouse lays the foundation of genome zoology. , 2003, Human molecular genetics.

[3]  David M. A. Martin,et al.  The Genome of the African Trypanosome Trypanosoma brucei , 2005, Science.

[4]  Wei Qian,et al.  Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. , 2000, Molecular biology and evolution.

[5]  Ziheng Yang,et al.  Computational Molecular Evolution , 2006 .

[6]  Yoshiyuki Suzuki.  Negative selection on neutralization epitopes of poliovirus surface proteins: implications for prediction of candidate epitopes for immunization. , 2004, Gene.

[7]  S. Pongor,et al.  Stimulation of Trypanosoma cruzi adenylyl cyclase by an alpha D-globin fragment from Triatoma hindgut: effect on differentiation of epimastigote to trypomastigote forms. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Saul.  Malaria vaccines based on the Plasmodium falciparum merozoite surface protein 3--should we avoid amino acid sequence polymorphisms or embrace them? , 2007, The Journal of infectious diseases.

[9]  H. Munro,et al.  Mammalian protein metabolism , 1964 .

[10]  R. Nielsen,et al.  Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites. , 2003, Genetics.

[11]  Z. Yang,et al.  Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. , 1998, Molecular biology and evolution.

[12]  K. Chang,et al.  Migration through the Extracellular Matrix by the Parasitic Protozoan Leishmania Is Enhanced by Surface Metalloprotease gp63 , 2003, Infection and Immunity.

[13]  Daniel Nilsson,et al.  Comparative Genomics of Trypanosomatid Parasitic Protozoa , 2005, Science.

[14]  J. Stevens,et al.  The molecular evolution of Trypanosomatidae. , 2001, Advances in parasitology.

[15]  S. Jeffery.  Evolution of Protein Molecules , 1979 .

[16]  J. McInerney,et al.  Evidence of Positive Darwinian Selection in Putative Meningococcal Vaccine Antigens , 2005, Journal of Molecular Evolution.

[17]  R. Cole,et al.  The Procyclin Repertoire of Trypanosoma brucei , 1999, The Journal of Biological Chemistry.

[18]  B. Haas,et al.  The Genome Sequence of Trypanosoma cruzi, Etiologic Agent of Chagas Disease , 2005, Science.

[19]  Ziheng Yang.  Neutral and adaptive protein evolution , 2006 .

[20]  F. Baralle,et al.  An alpha D-globin fragment from Triatoma infestans hindgut stimulates Trypanosoma cruzi adenylyl cyclase and promotes metacyclogenesis. , 1993, Biological research.

[21]  F. Spertini,et al.  Phase I Malaria Vaccine Trial with a Long Synthetic Peptide Derived from the Merozoite Surface Protein 3 Antigen , 2005, Infection and Immunity.

[22]  U. Magnusson,et al.  X-ray Structures of the Leucine-binding Protein Illustrate Conformational Changes and the Basis of Ligand Specificity* , 2004, Journal of Biological Chemistry.

[23]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[24]  Joseph P Bielawski,et al.  Accuracy and power of bayes prediction of amino acid sites under positive selection. , 2002, Molecular biology and evolution.

[25]  Erik L. L. Sonnhammer,et al.  A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences , 1998, ISMB.

[26]  N. Goldman,et al.  Codon-substitution models for heterogeneous selection pressure at amino acid sites. , 2000, Genetics.

[27]  Robert C. Edgar,et al.  MUSCLE: a multiple sequence alignment method with reduced time and space complexity , 2004, BMC Bioinformatics.

[28]  H. D. de Koning,et al.  Uptake of pentamidine in Trypanosoma brucei brucei is mediated by the P2 adenosine transporter and at least one novel, unrelated transporter. , 2001, Acta tropica.

[29]  Michael P Barrett,et al.  The trypanosomiases , 2003, The Lancet.

[30]  S. Gallati,et al.  Genetic variants of the TbAT1 adenosine transporter from African trypanosomes in relapse infections following melarsoprol therapy. , 2001, Molecular and biochemical parasitology.

[31]  D. Conway,et al.  Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection. , 2007, The Journal of infectious diseases.

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

[33]  T. Jukes.  CHAPTER 24 – Evolution of Protein Molecules , 1969 .

[34]  J. Barry,et al.  Expression of Procyclin mRNAs during Cyclical Transmission of Trypanosoma brucei , 2005, PLoS pathogens.

[35]  Ziheng Yang,et al.  Statistical methods for detecting molecular adaptation , 2000, Trends in Ecology & Evolution.

[36]  J. Donelson,et al.  The Genome of the African Trypanosome , 2002 .

[37]  Z. Yang,et al.  Accuracy and power of the likelihood ratio test in detecting adaptive molecular evolution. , 2001, Molecular biology and evolution.

[38]  R. Zoraghi,et al.  cAMP signalling in Trypanosoma brucei. , 2001, International journal for parasitology.

[39]  F. Quiocho,et al.  Structure of the L-leucine-binding protein refined at 2.4 A resolution and comparison with the Leu/Ile/Val-binding protein structure. , 1989, Journal of molecular biology.

[40]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[41]  A. Jackson.  Origins of amino acid transporter loci in trypanosomatid parasites , 2007, BMC Evolutionary Biology.

[42]  G. von Heijne,et al.  A new method for predkting signal sequence cleavage sites , 2022 .

[43]  R. Nielsen,et al.  Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. , 1998, Genetics.

[44]  R. Kaminsky,et al.  A nucleoside transporter from Trypanosoma brucei involved in drug resistance. , 1999, Science.

[45]  W. McMaster,et al.  Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. , 2002, Molecular and biochemical parasitology.

[46]  Structural analysis of adenylate cyclases from Trypanosoma brucei in their monomeric state , 2001, The EMBO journal.

[47]  P. Overath,et al.  The molecular phylogeny of trypanosomes: evidence for an early divergence of the Salivaria. , 1998, Molecular and biochemical parasitology.

[48]  Nick Goldman,et al.  Accuracy and Power of Statistical Methods for Detecting Adaptive Evolution in Protein Coding Sequences and for Identifying Positively Selected Sites , 2004, Genetics.

[49]  Anne-Mieke Vandamme,et al.  Mapping Sites of Positive Selection and Amino Acid Diversification in the HIV Genome , 2004, Genetics.

[50]  R. Nielsen,et al.  Pervasive adaptive evolution in mammalian fertilization proteins. , 2003, Molecular biology and evolution.

[51]  K. Ziegelbauer,et al.  Identification of invariant surface glycoproteins in the bloodstream stage of Trypanosoma brucei. , 1992, The Journal of biological chemistry.

[52]  L. Pearl,et al.  Crystal structure of AmiC: the controller of transcription antitermination in the amidase operon of Pseudomonas aeruginosa. , 1994, The EMBO journal.

[53]  Johannes Söding,et al.  The HHpred interactive server for protein homology detection and structure prediction , 2005, Nucleic Acids Res..

[54]  Matthew Hurles,et al.  Gene Duplication: The Genomic Trade in Spare Parts , 2004, PLoS biology.

[55]  L. Pearl,et al.  Structural adaptation to selective pressure for altered ligand specificity in the Pseudomonas aeruginosa amide receptor, amiC. , 2000, Protein engineering.

[56]  D. Conway,et al.  Naturally acquired antibodies to polymorphic and conserved epitopes of Plasmodium falciparum merozoite surface protein 3 , 2007, Parasite immunology.

[57]  S. Otto,et al.  The evolution of gene duplicates. , 2002, Advances in genetics.

[58]  L. Essen,et al.  Crystallization and preliminary X-ray analysis of the catalytic domain of the adenylate cyclase GRESAG4.1 from Trypanosoma brucei. , 2000, Acta crystallographica. Section D, Biological crystallography.