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Eichler Lab

Department of Genome Sciences,
University of Washington

Research Program


Genomic duplication followed by adaptive mutation is considered one of the primary forces for evolution of new gene function. Duplicated sequences are also dynamic regions of rapid structural change during the course of chromosome evolution. The long-term goal of our research is to understand the evolution, pathology and mechanism(s) of recent gene duplication and DNA transposition within the human genome.  Our research specifically addresses a new paradigm that has emerged in the past few years regarding the dynamic nature of human genome structure.  Particular chromosomal regions have been shown to be active in the acquisition, duplication and dispersal of large gene-containing genomic segments.  We hypothesize that these jumping genomic segments, also known as segmental duplications, are part of an ongoing evolutionary process that results in a novel form of large-scale DNA variation and contributes to rapid primate gene evolution.  At a structural level, duplications may be viewed as dynamic mutations (Fig. 1)–an initial event increases the probability of a second event.  Sequence homology created as a result of duplication increases the probability of additional rounds of gene conversion, unequal crossing-over and subsequent rearrangement.  Not surprisingly, many of the largest duplication blocks are substrates for recurrent chromosomal structural rearrangements associated with certain human diseases and disease susceptibility.  Compared to unique nonfunctional or neutral DNA, these particular areas of the genome represent hotspots of evolutionary and contemporary change. Their impact on human disease and evolution are only beginning to be understood.
Figure 1

Figure 1: Segmental Dynamic Mutation.  Non-allelic homologous recombination between blocks of segmental duplication (blue) during meiosis leads to microdeletion and microduplication of the unique region bracketed by duplications.  If the region contains dosage-sensitive genes (ABC), disease may result.  If not, the duplicated chromosome is predisposed to additional rounds of microdeletion and duplication with increased probability.