title: Reconstructing contiguous regions of an ancestral genome.
abstract: This article analyzes mammalian genome rearrangements at higher resolution than has been published to date. We identify 3171 intervals, covering approximately 92% of the human genome, within which we find no rearrangements larger than 50 kilobases (kb) in the lineages leading to human, mouse, rat, and dog from their most recent common ancestor. Combining intervals that are adjacent in all contemporary species produces 1338 segments that may contain large insertions or deletions but that are free of chromosome fissions or fusions as well as inversions or translocations >50 kb in length. We describe a new method for predicting the ancestral order and orientation of those intervals from their observed adjacencies in modern species. We combine the results from this method with data from chromosome painting experiments to produce a 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. Analysis of the predicted evolutionary breakpoints in the human lineage confirms certain published observations but disagrees with others. Although only a few mammalian genomes are currently sequenced to high precision, our theoretical analyses and computer simulations indicate that our results are reasonably accurate and that they will become highly accurate in the foreseeable future. Our methods were developed as part of a project to reconstruct the genome sequence of the last ancestor of human, dogs, and most other placental mammals.
authors.affiliation: Center for Comparative Genomics and Bioinformatics, Penn State University, University Park, Pennsylvania 16802, USA. jianma@bx.psu.edu
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Louxin
authors.initials: L
authors.lastname: Zhang
authors.forename: Bernard B
authors.initials: BB
authors.lastname: Suh
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Raney
authors.forename: Richard C
authors.initials: RC
authors.lastname: Burhans
authors.forename: W James
authors.initials: WJ
authors.lastname: Kent
authors.forename: Mathieu
authors.initials: M
authors.lastname: Blanchette
authors.forename: David
authors.initials: D
authors.lastname: Haussler
authors.forename: Webb
authors.initials: W
authors.lastname: Miller
mesh_terms: D000465:Algorithms; D000818:Animals; D001482:Base Composition; D020029:Base Pairing; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D020223:Chromosome Painting; D002875:Chromosomes; D003198:Computer Simulation; D004285:Dogs; D019143:Evolution, Molecular; D017353:Gene Deletion; D015321:Gene Rearrangement; D016678:Genome; D015894:Genome, Human; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D051381:Rats; D016415:Sequence Alignment / Q000379:methods; D012689:Sequence Homology, Nucleic Acid