Evan Eichler, UWash/HHMI, Human Genome Structural Variation, Disease and Evolution
Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Seattle.
Duplicated sequences are important sources for the evolution of new gene function within species and are also hotspots of genomic rearrangement. Humans and great apes have a preponderance of intrachromosomal duplications organized in an interspersed fashion as opposed to tandem which is the archetype in most other mammalian genomes. We have used this architectural feature to discover copy number variation associated with neurodevelopmental disease and rapidly evolving gene families. We have reconstructed the evolutionary history of these regions within the primate lineage. All of these data point to a burst of segmental duplication in the common ancestor of human and the apes in contrast to other mutational processes, which have slowed. I will show that much of the interspersed human duplication architecture is focused around core duplicons corresponding to the expansion of gene families that show strong signatures of positive selection and lack orthologs in other mammalian species. I will provide examples of potentially novel genes that have evolved within the human lineage and may be important in terms of brain function. Paradoxically, the duplication architecture has led to a high background rate of copy number variation mutations associated with neuropsychiatric and neurodevelopmental disease in the human species suggesting that novel adaptations and increased disease burden in our lineage are linked.
Location: Carl Icahn Lab 101
Date/Time: 04/16/12 at 4:15 pm - 04/16/12 at 5:15 pm
Category: Quantitative & Computational Biology
Department: Lewis-Sigler Institute