User:IanSwinburne

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Research Interests

Intron sequence is the major contributor to gene length for the lion’s share of our genes. In 1970, James Watson invoked transcriptional delays in models describing biological timing for lambda phage and their use of a long late operon. David Gubb, who noted that Drosophila’s Antennapedia and ultrabithorax genes owe their great lengths to large introns, formally distinguished the intron-delay hypothesis in 1986. With the knowledge that the development of the fly’s body plan is sensitive to the proper expression of these genes in space and time, he proposed that intron-length could contribute a time-delay to aid the orchestration of gene expression patterns. Mutants to directly substantiate the intron-delay hypothesis have been either elusive or inappropriately annotated as enhancers. Interestingly, a slightly slower RNA Polymerase mutant allele in the fly shares some phenotypes with ultrabithorax mutants. Gene length has increased during evolution: from short intron-less genes in prokaryotes, to primarily single introns in yeast genes that reach 1 kilobase in length, and to large, multi-intron genes such as the extreme 2.3 megabases encompassed by the human dystrophin gene. While a 2.3 megabases transcriptional unit may take more than 16 hours to transcribe, a functional role for gene length and for the periods of time it takes to transcribe different gene lengths remains unclear. A line of observations and phenomena suggest significant roles for intron-delays, particularly during developmental programs such as the maternal-zygotic transition, somitogenesis, and abdominal segmentation. To begin to address the role of gene length, I applied reductionism to answer three questions related to the intron-delay hypothesis: 1) What is the quantitative impact of intron-length on the timing and precision of gene expression? 2) How does intron-length influence gene expression when, in early G1, transcription must reinitiate after the mitotic constraint? 3) What impact does the intron-delay have on an auto-inhibition network predicted to oscillate with a period proportional to the time-delay?

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