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Published February 28, 2003 | Supplemental Material
Journal Article Open

Phylogenetic Shadowing of Primate Sequences to Find Functional Regions of the Human Genome

Abstract

Nonhuman primates represent the most relevant model organisms to understand the biology of Homo sapiens. The recent divergence and associated overall sequence conservation between individual members of this taxon have nonetheless largely precluded the use of primates in comparative sequence studies. We used sequence comparisons of an extensive set of Old World and New World monkeys and hominoids to identify functional regions in the human genome. Analysis of these data enabled the discovery of primate-specific gene regulatory elements and the demarcation of the exons of multiple genes. Much of the information content of the comprehensive primate sequence comparisons could be captured with a small subset of phylogenetically close primates. These results demonstrate the utility of intraprimate sequence comparisons to discover common mammalian as well as primate-specific functional elements in the human genome, which are unattainable through the evaluation of more evolutionarily distant species.

Additional Information

© 2003 American Association for the Advancement of Science. 9 December 2002; accepted 14 January 2003. We thank J.-F. Cheng for support with the sequencing infrastructure, the Zoological Society of San Diego for providing primate DNA samples, and I. Udalova and L. Pennacchio for useful discussions. M. Jordan contributed useful suggestions concerning statistical methods. This work was performed under the auspices of the U.S. Department of Energy's Office of Science, Biological and Environmental Research; by the University of California, Lawrence Berkeley National Laboratory under Contract No. DEAC0376SF00098; supported by Grant #HL66728, Berkeley-PGA, under the Programs for Genomic Application, funded by National Heart, Lung, and Blood Institute, USA. L.P. was partially supported by a grant from NIH (R01-HG02362-01).

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