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Title: Predicting plasmid host range with dinucleotide analysis


1
Predicting plasmid host range with dinucleotide
analysis Haruo Suzuki, Masahiro Sota, Celeste J.
Brown, and Eva M. Top Department of Biological
Sciences, University of Idaho, Moscow, Idaho 83844
R-071
Contact Information Department of Biological
Sciences, PO Box 443051, University of Idaho,
Moscow, ID 83844-3051, Phone 1-208-885-8858
Fax 1-208-885-7905, E-mail hsuzuki_at_uidaho.edu
  • INTRODUCTION
  • Bacterial plasmids are ubiquitous mobile elements
    that serve as a pool of many host-beneficial
    traits such as antibiotic resistance 1. To
    understand the role of plasmids in horizontal
    gene transfer, we need to gain insight into the
    life history of the plasmids, i.e., the range
    of hosts in which they have evolved. Since
    extensive data support the proposal that foreign
    DNA acquires the host's nucleotide composition
    during long-term residence (amelioration) 2,
    comparison of nucleotide composition of plasmids
    and chromosomes could shed light on a plasmids'
    life history.
  • The average absolute difference, ?, has been
    commonly used to measure differences in
    dinucleotide relative abundance or 'genomic
    signature' between bacterial chromosomes and
    plasmids 3. Here, we introduced Mahalanobis
    distance, D2, which accounts for the
    variance-covariance structure of the chromosomal
    signatures.


Was virulence plasmid pO157 acquired from
Yersinia pestis? Bacterial strains most similar
in dinucleotide composition to plasmid pO157 from
enterohemorrhagic Escherichia coli O157H7 EDL933.
Mahalanobis distance identifies plausible hosts
of Bacillus anthracis virulence plasmid
pXO1 Five highest ranking bacterial strains
based on Mahalanobis distance D2 (A) and average
absolute difference ? (B) for plasmid pXO1.
GOAL To compare performance of Mahalanobis
distance and commonly used ?-distance in
identifying plasmids hosts based on dinucleotide
composition similarity
  • Yersinia pestis, agent of the bubonic plague,
    were identified as potential long-term hosts of
    plasmid pO157.

Inferring potential hosts of a plasmid from
unknown host Bacterial strains most similar in
dinucleotide composition to broad-host-range
plasmid pB10 captured directly from environmental
samples 4.
  • The D2 value ranked plausible hosts (B. cereus
    sensu lato) first, while the ? value ranked
    unlikely hosts first.
  • Different species comprising the B. cereus sensu
    lato group are largely defined by differences in
    plasmids, while the chromosomes are highly
    similar.
  • The known natural host of pXO1, B. anthracis,
    ranked 5 based on the D2 value, and only 10 based
    on the ? value.
  • METHODS
  • Analyses were implemented using G-language Genome
    Analysis Environment, available at
    http//www.g-language.org. Complete genome
    sequences of 195 chromosomes and 412 plasmids of
    Bacteria were retrieved from the NCBI ftp site
    (ftp//ftp.ncbi.nih.gov/genomes/Bacteria).
  • Dinucleotide relative abundance (xij) is defined
    as
  • where fi and fj denote the frequency of the
    mononucleotide i and j respectively (i,j ?
    A,C,G,T) and fij the frequency of the
    dinucleotide ij.
  • We compared two distance measures to quantify the
    dinucleotide relative abundance difference
    between DNA sequences.
  • Average absolute difference, ?, used previously
  • where xij and yij denote the relative abundance
    value of the dinucleotide ij for the plasmid and
    the chromosomal segment, respectively.
  • Mahalanobis distance, D2, introduced in this
    study

Mahalanobis distance performs better to identify
plasmids hosts Distributions of ranks of
dinucleotide relative abundance similarities
between plasmids and their known natural hosts
based on Mahalanobis distance D2 (A) and average
absolute difference ? (B)
  • Members of the ß-Proteobacteria were identified
    as long-term evolutionary hosts of plasmid pB10,
    which is in agreement with experimental evidence
    of the plasmids replication range.
  • CONCLUSIONS
  • Mahalanobis distance performs better than
    commonly used ?-distance to identify known
    natural hosts of plasmids based on dinucleotide
    composition similarity.
  • Dinucleotide analysis with Mahalanobis distance
    can also be used to infer potential hosts of
    plasmids, which can then be experimentally tested.

_
Acknowledgements We thank members of IBEST
(Initiative for Bioinformatics and Evolutionary
Studies) at the University of Idaho for useful
discussions. This work was supported by National
Science Foundation (EF-0627988) National
Institutes of Health (P20RR016454,
P20RR16448). References 1 Frost LS et al.
(2005) Nat Rev Microbiol, 3, 722-732. 2
Lawrence JG and Ochman H (1997) J Mol Evol, 44,
383-397. 3 Campbell A et al. (1999) Proc Natl
Acad Sci USA, 96, 9184-9189. 4 Schlüter A et
al. (2003) Microbiology 1493139-53.
  • The plasmid-host pairs tended to rank higher when
    using the D2 value compared to the ? value
    (Wilcoxon signed rank test p lt 10-15).
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