Reconstructing contiguous regions of an ancestral genome

The increasing number of mammalian genome sequences becoming available provides scientists with dramatic opportunities to better understand human evolution. Comparative genome analysis enables us to computationally reconstruct an ancestral mammalian genome by comparing the genomes of living descendants.;Here, we introduce new methods and tools for identifying large-scale rearrangements and reconstructing contiguous ancestral regions. We discuss several critical problems, including the identification of conserved segments that have not been rearranged through evolution of the studied species, the prediction of ancestral order of these conserved segments, and the computational evaluation of the reconstruction.;Using these methods, several analyses have been carried out. In particular, we analyze mammalian genome rearrangements at higher resolution than has been published to date. In the lineages leading to human, mouse, rat and dog from their most recent common ancestor, we identify 1338 conserved intervals over 50Kb in length. Using our algorithm for predicting the ancestral order and orientation of those intervals from their observed adjacencies in modern species, we produce a karyotype map of an early mammalian genome that accounts for 96.8% of the available human genome sequence data. The precision is further increased by mapping inversions as small as 31 bp. We also discuss the biological insights gained from these analyses. Although only a few mammalian genomes are currently sequenced to high precision, our evaluation indicates that our results are reasonably accurate, and that they will become highly accurate in the foreseeable future.