Title: "Sequence Conservation at Odz4: An Evolutionary Mechanism of Gene Diversity?"
Speaker: Dr. Amy Lossie, Department of Animal Science, Purdue University
Place: Electrical Engineering (EE) 270; February 13, 2007, Tuesday, 4:30pm


The Odz4 allelic series is comprised of six different mutants, each with defects in mesoderm development that cause strikingly different phenotypes. The most severe allele fails to undergo gastrulation, while the least severe survives to adulthood with defects in bone formation. This phenotypic pleiotropy foretells the underlying transcriptional, genomic and protein complexity of the 735 kb Odz4 locus, which encodes more than 20 distinct temporally and spatially restricted transcripts. Using comparative genomics, we sought to identify alternate promoters, 3'UTRs and conserved non-coding sequences (NCS) that regulate the numerous tissue-specific Odz4 transcripts. We compared 1.3 Mb of genomic DNA flanking Odz4 from mouse, rat, human, chimpanzee, dog and chicken and identified 428 NCS (>50bp) along this region, with 102 sites conserved to chicken. Strikingly, while 92 NCS identified in mouse/chicken comparisons lie within Odz4, only 10 reside in flanking sequences. Twenty-eight of these are >200 bp and show 70% identity between mouse and chicken, emphasizing the high degree of evolutionary conservation found along the Odz4 locus. Further comparisons with teleosts detected 7 NCS that span 450 million years of evolution. We chose these large, highly conserved NCS for further investigation. Although none contain components suggestive of cis-regulatory elements, 3 could harbor alternative 3'UTRs, and we are currently using experimental methods to understand how these sites regulate tissue-specific expression of Odz4. Our data reveal that over 100 elements could act coordinately to regulate transcription of Odz4, highlighting locus complexity as an evolutionary alternative to one gene, one protein.

Associated Reading:
Amy C. Lossie, Hisashi Nakamura, Sharon E. Thomas and Monica J. Justice. 2005. Mutation of l7Rn3 Shows That Odz4 Is Required for Mouse Gastrulation. Genetics. 169: 285-299.

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