DendroPy includes native infrastructure for phylogenetic sequence simulation on DendroPy trees under the HKY model. Being pure-Python, however, it is a little slow. If Seq-Gen is installed on your system, though, you can take advantage of the dendropy.interop.seqgen.SeqGen wrapper to efficiently simulate sequences under a wide variety of models. The following examples should be enough to get started, and the class is simple and straightforward enough so that all options should be pretty much self-documented.
#! /usr/bin/env python import dendropy from dendropy.interop import seqgen trees = dendropy.TreeList.get_from_path("pythonidae.mcmc.nex", "nexus") s = seqgen.SeqGen() # generate one alignment per tree # as substitution model is not specified, defaults to a JC model # will result in a DataSet object with one DnaCharacterMatrix per input tree d0 = s.generate(trees) print len(d0.char_matrices) # instruct Seq-Gen to scale branch lengths by factor of 0.1 # note that this does not modify the input trees s.scale_branch_lens = 0.1 # more complex model s.char_model = seqgen.SeqGen.GTR s.state_freqs = [0.4, 0.4, 0.1, 0.1] s.general_rates = [0.8, 0.4, 0.4, 0.2, 0.2, 0.1] d1 = s.generate(trees) print len(d1.char_matrices)