\name{dist.dna}
\alias{dist.dna}
\title{Pairwise Distances from DNA Sequences}
\usage{
dist.dna(x, model = "K80", variance = FALSE,
         gamma = FALSE, pairwise.deletion = FALSE,
         base.freq = NULL, as.matrix = FALSE)
}
\arguments{
  \item{x}{a matrix, a data frame, or a list containing the DNA
    sequences (the latter can be taken from, e.g.,
    \code{\link{read.GenBank}}).}
  \item{model}{a character string specifying the evlutionary model to be
    used; must be one of \code{"raw"}, \code{"JC69"}, \code{"K80"} (the
    default), \code{"F81"}, \code{"K81"}, \code{"F84"}, \code{"T92"},
    \code{"TN93"}, or \code{"GG95"}.}
  \item{variance}{a logical indicating whether to compute the variances
    of the distances; defaults to \code{FALSE} so the variances are not
    computed.}
  \item{gamma}{a value for the gamma parameter which is possibly used to
    apply a gamma correction to the distances (by default \code{gamma =
      FALSE} so no correction is applied).}
  \item{pairwise.deletion}{a logical indicating whether to delete the
    sites with missing data in a pairwise way. The default is to delete
    the sites with at least one missing data for all sequences.}
  \item{base.freq}{the base frequencies to be used in the computations
    (if applicable, i.e. if \code{method = "F84"}). By default, the
    base frequencies are computed from the whole sample of sequences.}
  \item{as.matrix}{a logical indicating whether to return the results as
    a matrix. The default is to return an object of class
    \link[stats]{dist}.}
}
\description{
  These functions compute a matrix of pairwise distances from DNA
  sequences using a model of DNA evolution. Eight substitution models
  (and the raw distance) are currently available.
}
\details{
  As from ape 1.5, the interface and the computational part of this
  function have been completely rewritten.

  The molecular evolutionary models available through the option
  \code{model} have been extensively described in the literature. A
  brief description is given below; more details can be found in the
  References.

  \item{``raw''}{This is simply the proportion of sites that differ
    between each pair of sequences. This may be useful to draw
    ``saturation plots''. The options \code{variance} and \code{gamma}
    have no effect, but \code{pairwise.deletion} can.}

  \item{``JC69''}{This model was developed by Jukes and Cantor (1969). It
    assumes that all substitutions (i.e. a change of a base by another
    one) have the same probability. This probability is the same for all
    sites along the DNA sequence. This last assumption can be relaxed by
    assuming that the substition rate varies among site following a
    gamma distribution which parameter must be given by the user. By
    default, no gamma correction is applied. Another assumption is that
    the base frequencies are balanced and thus equal to 0.25.}

  \item{``K80''}{The distance derived by Kimura (1980), sometimes referred
    to as ``Kimura's 2-parameters distance'', has the same underlying
    assumptions than the Jukes--Cantor distance except that two kinds of
    substitutions are considered: transitions (A <-> G, C <-> T), and
    transversions (A <-> C, A <-> T, C <-> G, G <-> T). They are assumed
    to have different probabilities. A transition is the substitution of
    a purine (C, T) by another one, or the substitution of a pyrimidine
    (A, G) by another one. A transversion is the substitution of a
    purine by a pyrimidine, or vice-versa. Both transition and
    transversion rates are the same for all sites along the DNA
    sequence. Jin and Nei (1990) modified the Kimura model to allow for
    variation among sites following a gamma distribution. Like for the
    Jukes--Cantor model, the gamma parameter must be given by the
    user. By default, no gamma correction is applied.}

  \item{``F81''}{Felsenstein (1981) generalized the Jukes--Cantor model
    by relaxing the assumption of equal base frequencies. The formulae
    used in this function were taken from McGuire et al. (1999)}.

  \item{``K81''}{Kimura (1981) generalized his model (Kimura 1980) by
    assuming different rates for two kinds of transversions: A <-> C and
    G <-> T on one side, and A <-> T and C <-> G on the other. This is
    what Kimura called his ``three substitution types model'' (3ST), and
    is sometimes referred to as ``Kimura's 3-parameters distance''}.

  \item{``F84''}{This model generalizes ``K80'' by relaxing the
    assumption of equal base frequencies. It was first introduced by
    Felsenstein in 1984 in Phylip, and is fully described by Felsenstein
    and Churchill (1996). The formulae used in this function were taken
    from McGuire et al. (1999)}.

  \item{``T92''}{Tamura (1992) generalized the Kimura model by relaxing
    the assumption of equal base frequencies. This is done by taking
    into account the bias in G+C content in the sequences. The
    substitution rates are assumed to be the same for all sites along
    the DNA sequence.}

  \item{``TN93''}{Tamura and Nei (1993) developed a model which assumes
    distinct rates for both kinds of transition (A <-> G versus C <->
    T), and transversions. The base frequencies are not assumed to be
    equal and are estimated from the data. A gamma correction of the
    inter-site variation in substitution rates is possible.}

  \item{``GG95''}{Galtier and Gouy (1995) introduced a model where the
    G+C content may change through time. Different rates are assumed for
    transitons and transversions.}
}
\value{
  an object of class \link[stats]{dist} (by default), or a numeric
  matrix if \code{as.matrix = TRUE}.

  If \code{variance = TRUE} an attribute called \code{"variance"} is
  given to the returned object.
}
\references{
  Felsenstein, J. (1981) Evolutionary trees from DNA sequences: a
  maximum likelihood approach. \emph{Journal of Molecular Evolution},
  \bold{17}, 368--376.

  Felsenstein, J. and Churchill, G. A. (1996) A Hidden Markov model
  approach to variation among sites in rate of evolution.
  \emph{Molecular Biology and Evolution}, \bold{13}, 93--104.

  Galtier, N. and Gouy, M. (1995) Inferring phylogenies from DNA
  sequences of unequal base compositions. \emph{Proceedings of the
    National Academy of Sciences USA}, \bold{92}, 11317--11321.

  Jukes, T. H. and Cantor, C. R. (1969) Evolution of protein
  molecules. in \emph{Mammalian Protein Metabolism}, ed. Munro, H. N.,
  pp. 21--132, New York: Academic Press.

  Kimura, M. (1980) A simple method for estimating evolutionary rates of
  base substitutions through comparative studies of nucleotide
  sequences. \emph{Journal of Molecular Evolution}, \bold{16}, 111--120.

  Kimura, M. (1981) Estimation of evolutionary distances between
  homologous nucleotide sequences. \emph{Proceedings of the National
    Academy of Sciences USA}, \bold{78}, 454--458.

  Jin, L. and Nei, M. (1990) Limitations of the evolutionary parsimony
  method of phylogenetic analysis. \emph{Molecular Biology and
    Evolution}, \bold{7}, 82--102.

  McGuire, G., Prentice, M. J. and Wright, F. (1999). Improved error
  bounds for genetic distances from DNA sequences. \emph{Biometrics},
  \bold{55}, 1064--1070.

  Tamura, K. (1992) Estimation of the number of nucleotide substitutions
  when there are strong transition-transversion and G + C-content
  biases. \emph{Molecular Biology and Evolution}, \bold{9}, 678--687.

  Tamura, K. and Nei, M. (1993) Estimation of the number of nucleotide
  substitutions in the control region of mitochondrial DNA in humans and
  chimpanzees. \emph{Molecular Biology and Evolution}, \bold{10}, 512--526.
}
\author{Emmanuel Paradis \email{paradis@isem.univ-montp2.fr}}
\seealso{
  \code{\link{read.GenBank}}, \code{\link{read.dna}},
  \code{\link{write.dna}}, \code{\link{dist.gene}},
  \code{\link{dist.phylo}}, \code{\link[stats]{dist}}
}
\keyword{manip}
\keyword{multivariate}