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An ancient genome sequence of 1.1 Mb is reconstructed around the CFTR locus using actual genomic sequences form 19 extant mammals. The reconstruction is accurate and allows the identification of the features in modern species, such as remnants of ancient transposon insertions that were not identified by direct analysis.

Mammalian genome rearrangements are analyzed at higher resolution and a new method is described for predicting ancestral order and orientation of those intervals from their observed adjacencies in modern species. These methods are developed as part of a project to reconstruct the genome sequence of the last ancestor of human, dogs and most other placental mammals.

An algorithm relying on the principle that cis-regulatory modules (CRMs) generally contain several phylogenetically conserved binding sites for different transcription-factors (TFs) is described. It reveals that CRM density varies widely across the genome, with CRM-rich regions often being located near genes encoding transcription factors involved in development.

Threaded blockset, a novel generalization of the classic notion of a multiple alignment, is defined. A new computer program called threaded blockset aligner(TBA) builds a threaded blockset and is designed to be appropriate for aligning many megabase-sized regions of multiple mammalian genomes.

The authors have investigated genome function. They report that available genome sequences are insufficient for the comprehensive identification of multi-species conserved sequences in the human genome.

Phylogenic footprinting is a method for the discovery of regulatory elements in a set of orthologous regulatory regions from multiple species. The program reports all sets of patterns with the lowest parsimony scores calculated with respect to the phylogenic tree relating the input species.