Genomic Signatures of Distributive Conjugal Transfer among Mycobacteria

Distributive conjugal transfer (DCT) is a newly described mechanism of lateral gene transfer (LGT) that results in a mosaic transconjugant structure, similar to the products of meiosis. We have tested popular LGT detection methods on whole-genome sequence data from experimental DCT transconjugants and used the best performing methods to compare genomic signatures of DCT with those of LGT through natural transformation, conjugative plasmids, and mobile genetic elements (MGE). We found that DCT results in transfer of larger chromosomal segments, that these segments are distributed more broadly around the chromosome, and that a greater proportion of the chromosome is affected by DCT than by other mechanisms of LGT. We used the best performing methods to characterize LGT in Mycobacterium canettii, the mycobacterial species most closely related to Mycobacterium tuberculosis. Patterns of LGT among M. canettii were highly distinctive. Gene flow appeared unidirectional, from lineages with minimal evidence of LGT to isolates with a substantial proportion (6–13%) of sites identified as recombinant. Among M. canettii isolates with evidence of LGT, recombinant fragments were larger and more evenly distributed relative to bacteria that undergo LGT through natural transformation, conjugative plasmids, and MGE. Spatial bias in M. canettii was also unusual in that patterns of recombinant fragment sharing mirrored overall phylogenetic structure. Based on the proportion of recombinant sites, the size of recombinant fragments, their spatial distribution and lack of association with MGE, as well as unidirectionality of DNA transfer, we conclude that DCT is the predominant mechanism of LGT among M. canettii.

[1]  M. Tsukamura,et al.  Transformation of isoniazid and streptomycin resistance in Mycobacterium avium by the desoxyribonucleate derived from isoniazid- and streptomycin-double-resistant cultures. , 1960, The American review of respiratory disease.

[2]  M. Norgard,et al.  Physiological factors involved in the transformation of Mycobacterium smegmatis , 1978, Journal of bacteriology.

[3]  S. Sawyer.  Statistical tests for detecting gene conversion. , 1989, Molecular biology and evolution.

[4]  T. Petes,et al.  Meiotic recombination hot spots and cold spots , 2001, Nature Reviews Genetics.

[5]  J. T. Crawford,et al.  Simultaneous infection with multiple strains of Mycobacterium tuberculosis. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  P. Fearnhead,et al.  A coalescent-based method for detecting and estimating recombination from gene sequences. , 2002, Genetics.

[7]  K. Derbyshire,et al.  Unconventional conjugal DNA transfer in mycobacteria , 2003, Nature Genetics.

[8]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[9]  C. Locht,et al.  Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence area , 2003, Molecular microbiology.

[10]  K. Derbyshire,et al.  The RD1 virulence locus of Mycobacterium tuberculosis regulates DNA transfer in Mycobacterium smegmatis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Le Flèche,et al.  High Genetic Diversity Revealed by Variable-Number Tandem Repeat Genotyping and Analysis of hsp65 Gene Polymorphism in a Large Collection of “Mycobacterium canettii” Strains Indicates that the M. tuberculosis Complex Is a Recently Emerged Clone of “M. canettii” , 2004, Journal of Clinical Microbiology.

[12]  H. Matsuda,et al.  Biased biological functions of horizontally transferred genes in prokaryotic genomes , 2004, Nature Genetics.

[13]  E. Krzywińska,et al.  Naturally occurring horizontal gene transfer and homologous recombination in Mycobacterium. , 2004, Microbiology.

[14]  V. Chernick.  A new evolutionary scenario for the Mycobacterium tuberculosis complex. , 2004, Pediatric pulmonology.

[15]  Christopher M Thomas,et al.  Mechanisms of, and Barriers to, Horizontal Gene Transfer between Bacteria , 2005, Nature Reviews Microbiology.

[16]  Vladimir N. Minin,et al.  Dual multiple change-point model leads to more accurate recombination detection , 2005, Bioinform..

[17]  R. Brosch,et al.  Ancient Origin and Gene Mosaicism of the Progenitor of Mycobacterium tuberculosis , 2005, PLoS pathogens.

[18]  Jonathan Pevsner,et al.  Basic Local Alignment Search Tool (BLAST) , 2005 .

[19]  K. Derbyshire,et al.  Chromosomal DNA transfer in Mycobacterium smegmatis is mechanistically different from classical Hfr chromosomal DNA transfer , 2005, Molecular microbiology.

[20]  J. Townsend,et al.  Horizontal gene transfer, genome innovation and evolution , 2005, Nature Reviews Microbiology.

[21]  D. Bryant,et al.  A Simple and Robust Statistical Test for Detecting the Presence of Recombination , 2006, Genetics.

[22]  D. Huson,et al.  Application of phylogenetic networks in evolutionary studies. , 2006, Molecular biology and evolution.

[23]  G. B. Golding,et al.  Lateral gene transfer in Mycobacterium avium subspecies paratuberculosis. , 2006, Canadian journal of microbiology.

[24]  A. Auton,et al.  Recombination rate estimation in the presence of hotspots. , 2007, Genome research.

[25]  D. Falush,et al.  Inference of Bacterial Microevolution Using Multilocus Sequence Data , 2007, Genetics.

[26]  Vladimir N. Minin,et al.  cBrother: relaxing parental tree assumptions for Bayesian recombination detection , 2007, Bioinform..

[27]  K. Derbyshire,et al.  The specialized secretory apparatus ESX‐1 is essential for DNA transfer in Mycobacterium smegmatis , 2008, Molecular microbiology.

[28]  Steven J. M. Jones,et al.  Circos: an information aesthetic for comparative genomics. , 2009, Genome research.

[29]  K. Nguyen,et al.  LpqM, a Mycobacterial Lipoprotein-Metalloproteinase, Is Required for Conjugal DNA Transfer in Mycobacterium smegmatis , 2009, Journal of bacteriology.

[30]  M. Behr,et al.  Phylogenetic detection of horizontal gene transfer during the step-wise genesis of Mycobacterium tuberculosis , 2009, BMC Evolutionary Biology.

[31]  V. Barbe,et al.  Non Mycobacterial Virulence Genes in the Genome of the Emerging Pathogen Mycobacterium abscessus , 2009, PloS one.

[32]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[33]  D. Falush,et al.  Natural Transformation of Helicobacter pylori Involves the Integration of Short DNA Fragments Interrupted by Gaps of Variable Size , 2009, PLoS pathogens.

[34]  X. Didelot,et al.  A comparison of homologous recombination rates in bacteria and archaea , 2009, The ISME Journal.

[35]  N. Perna,et al.  progressiveMauve: Multiple Genome Alignment with Gene Gain, Loss and Rearrangement , 2010, PloS one.

[36]  D. Falush,et al.  Inference of Homologous Recombination in Bacteria Using Whole-Genome Sequences , 2010, Genetics.

[37]  K. Nguyen,et al.  Mycobacterial Biofilms Facilitate Horizontal DNA Transfer between Strains of Mycobacterium smegmatis , 2010, Journal of bacteriology.

[38]  M. DePristo,et al.  A framework for variation discovery and genotyping using next-generation DNA sequencing data , 2011, Nature Genetics.

[39]  J. Burton,et al.  Rapid Pneumococcal Evolution in Response to Clinical Interventions , 2011, Science.

[40]  M. Daffé,et al.  Clinical characteristics of the smooth tubercle bacilli 'Mycobacterium canettii' infection suggest the existence of an environmental reservoir. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[41]  J. Corander,et al.  Restricted Gene Flow among Hospital Subpopulations of Enterococcus faecium , 2012, mBio.

[42]  J. Corander,et al.  Phylogeographic variation in recombination rates within a global clone of methicillin-resistant Staphylococcus aureus , 2012, Genome Biology.

[43]  E. Rocha,et al.  After the bottleneck: Genome-wide diversification of the Mycobacterium tuberculosis complex by mutation, recombination, and natural selection. , 2012, Genome research.

[44]  M. Hattori,et al.  Genome-Wide Survey of Mutual Homologous Recombination in a Highly Sexual Bacterial Species , 2012, Genome biology and evolution.

[45]  R. Stepanauskas,et al.  High-throughput single-cell sequencing identifies photoheterotrophs and chemoautotrophs in freshwater bacterioplankton , 2011, The ISME Journal.

[46]  J. Corander,et al.  Detection of recombination events in bacterial genomes from large population samples , 2011, Nucleic acids research.

[47]  K. Holt,et al.  Out-of-Africa migration and Neolithic co-expansion of Mycobacterium tuberculosis with modern humans , 2013, Nature Genetics.

[48]  J. Corander,et al.  The Evolutionary Path to Extraintestinal Pathogenic, Drug-Resistant Escherichia coli Is Marked by Drastic Reduction in Detectable Recombination within the Core Genome , 2013, Genome biology and evolution.

[49]  E. Willery,et al.  Genome analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of the etiologic agent of tuberculosis , 2013, Nature Genetics.

[50]  Michael Roberts,et al.  The MaSuRCA genome assembler , 2013, Bioinform..

[51]  J. Corander,et al.  Recent Recombination Events in the Core Genome Are Associated with Adaptive Evolution in Enterococcus faecium , 2013, Genome biology and evolution.

[52]  Omar E. Cornejo,et al.  The Role of Selection in Shaping Diversity of Natural M. tuberculosis Populations , 2013, PLoS pathogens.

[53]  M. Palumbo,et al.  Distributive Conjugal Transfer in Mycobacteria Generates Progeny with Meiotic-Like Genome-Wide Mosaicism, Allowing Mapping of a Mating Identity Locus , 2013, PLoS biology.

[54]  Christopher T. Small,et al.  Zoonotic simian foamy virus in Bangladesh reflects diverse patterns of transmission and co-infection , 2013, Emerging Microbes & Infections.

[55]  Allison D. Griggs,et al.  Emergence of Epidemic Multidrug-Resistant Enterococcus faecium from Animal and Commensal Strains , 2013, mBio.

[56]  E. Koonin,et al.  Horizontal Gene Transfer Can Rescue Prokaryotes from Muller’s Ratchet: Benefit of DNA from Dead Cells and Population Subdivision , 2013, G3: Genes, Genomes, Genetics.

[57]  C. Fraser,et al.  Heterogeneity in the Frequency and Characteristics of Homologous Recombination in Pneumococcal Evolution , 2014, PLoS genetics.