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Non-human Primate Genome Sequencing

General Considerations The long-term goal of non-human primate genome sequencing has been to annotate the genetic differences that have emerged over the last 60-70 million years of primate evolution. Embedded in these differences are the changes that have shaped evolutionary divergence and produced our unique human traits. Because differences rather than conserved sequences represent the major findings, high quality sequence is required. With the high quality data it will be possible to detect subtle changes in the primary structure of genes, which is important since even single amino acid differences can be key contributors to morphological differences. Similarly the important changes in the sequence of gene regulatory regions may involve only small numbers of DNA bases. Additionally, the important differences can involve large-scale genome rearrangements, including duplications and other structural rearrangements. Scaffolds built from BAC-end sequences and/or BAC skims can facilitate identification of the rearrangements, but cannot solve the pressing question of what are the precise events in divergence of this class of sequence that occurs between closely related species. We therefore advocate that one path to the general improvement and addition of value to primate genome sequences is to specifically select regions known to be involved in duplications and other structural rearrangement for further study. In practice this involves selection of individual large insert clones that capture these events, followed by their additional analysis to near-finished DNA sequencing standards.. This approach that aims to refine selected parts of primate genomes is different but complementary to the goals stated elsewhere of globally improving the knowledge of rearrangements across whole genomes, and other proposals to refine regions in draft genomes that contain genes. Overall, the current proposal shares with previous recommendations the general aim of pursuing fewer index primate species sequenced at higher quality, rather than many at low quality. Three criteria have been considered in the selection of non-human primate genome sequencing targets: 1) phylogenetic position with respect to human; 2) utility for identification of primate-specific regulatory elements; and 3) biomedical relevance in cases where other factors were equal. 1) Primate Phylogenetic Nodes. Past work has documented that there are seven distinct phylogenetic branchpoints between human and non-human primate species. Each of these nodes provides considerable power for annotation of the human genome, revealing those elements that have been altered in the evolution of the human species. Multiple species comparisons are expected to be significantly more informative than individual pairwise …