Reconstructing large regions of an ancestral mammalian genome in silico
It is believed that most modern
mammalian lineages arose from a series of
rapid speciation events near the Cretaceous-Tertiary boundary. It is
shown that such a phylogeny makes the common ancestral genome sequence an ideal
target for reconstruction. Simulations suggest that with methods currently available we can expect to get 98% of
the bases correct in reconstructing megabase scale euchromatic regions of an
eutherian ancestral genome from the genomes of approximately 20 optimally
chosen modern mammals. Using actual genomic sequences from 19 extant mammals,
we reconstruct 1.1 Mb of ancient genome sequence around the CFTR locus.
Detailed examination suggests the reconstruction is accurate and that it allows
us to identify features in modern species, such as remnants of ancient
transposon insertions, that were not identified by direct analysis. Tracing the
predicted evolutionary history of the bases in the reconstructed region, estimates
are made of the amount of DNA turnover due to insertion, deletion and
substitution in the different placental mammalian lineages since the common
eutherian ancestor, showing considerable variation between lineages. This talk
will focus on the algorithmic issues of this reconstruction.