  How natural selection acts to limit the proliferation of transposable
elements (TEs) in genomes has been of interest to evolutionary biologists for
many years. To describe TE dynamics in populations, many previous studies have
used models of transposition-selection equilibrium that rely on the assumption
of a constant rate of transposition. However, since TE invasions are known to
happen in bursts through time, this assumption may not be reasonable in natural
populations. Here we propose a test of neutrality for TE insertions that does
not rely on the assumption of a constant transposition rate. We consider the
case of TE insertions that have been ascertained from a single haploid
reference genome sequence and have subsequently had their allele frequency
estimated in a population sample. By conditioning on the age of an individual
TE insertion (using information contained in the number of substitutions that
have occurred within the TE sequence since insertion), we determine the
probability distribution for the insertion allele frequency in a population
sample under neutrality. Taking models of varying population size into account,
we then evaluate predictions of our model against allele frequency data from
190 retrotransposon insertions sampled from North American and African
populations of Drosophila melanogaster. Using this non-equilibrium model, we
are able to explain about 80% of the variance in TE insertion allele
frequencies based on age alone. Controlling both for nonequilibrium dynamics of
transposition and host demography, we provide evidence for negative selection
acting against most TEs as well as for positive selection acting on a small
subset of TEs. Our work establishes a new framework for the analysis of the
evolutionary forces governing large insertion mutations like TEs, gene
duplications or other copy number variants.
