Reconstructing large regions of an ancestral mammalian genome in silico

Abstract

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 ∼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. In coming years, such reconstructions may help in identifying and understanding the genetic features common to eutherian mammals and may shed light on the evolution of human or primate-specific traits

Using genomic data to unravel the root of the placental mammal phylogeny

“…These data will facilitate the assembly of larger data sets for analysis and will increase the ease with which corroborating rare genomic changes are identified Kriegs et al 2006;Nishihara et al 2006;Rokas and Carroll 2006). Moreover, the data will allow an accurate prediction of the evolutionary history of those species at all scales of evolutionary events, down to nucleotide resolution (Blanchette et al 2004). At one level, phylogenetic relationships correspond to the largest-scale evolutionary event, i.e., speciation, in a long list that includes chromosome fission and fusion, large-scale duplication, insertion of interspersed repeats, deletions, expansion/contraction of tandem repeats, and nucleotide substitutions, among others.…”

“…The exact placement of the root of the placental mammal tree has implications for inferring ancestral genomic sequences and genomes (Blanchette et al 2004;Ma et al 2006), as well as the early biogeographic history of placental mammals (Eizirik et al 2001;Madsen et al 2001;Murphy et al 2001b;Springer et al 2003;Hunter and Janis 2006). However, it has proved to be elusive Springer et al 2004;Kriegs et al 2006), and three hypotheses remain ( Fig.…”

New Methods for Detecting Lineage-Specific Selection

“…In addition, it turns out to be straightforward to integrate this indel model into a phylo-HMM (see full paper at http://www.bscb.cornell.edu/Homepages/Adam Siepel/ dless.pdf). This approach, of course, is only as good as the accuracy of the alignment and the indel history, but simulation experiments suggest that their accuracy is quite good, at least for mammalian genomes at modest evolutionary distances [22].…”

“…Briefly, we reconstruct an "indel history" (a history of insertion and deletion events on all branches of the tree) by parsimony, using a slightly modified version of the inferAncestors program [22]. We then compute emission probabilities of indels for a phylo-HMM conditional on this history.…”

Branching out

“…"My interest is to trace how modern human chromosomes have evolved from our ancestor, " he says. David Haussler of the University of California, Santa Cruz, and his collaborators want to peer even further back in time 5 . They are analysing sequence data from across the animal kingdom to reconstruct the genome of the ancestor of placental mammals, which lived around the time of the dinosaurs more than 75 million years ago.…”