Evolving contributions of the origin recognition complex (ORC) to subtelomeric chromatin

点击翻译按钮获取中文摘要

Gene duplication is a driving force in molecular evolution, as it provides new genetic material that can be adapted to serve different purposes in living organisms. This project is aimed at elucidating how duplicate genes diverge and their encoded proteins acquire distinct properties. In particular, the research will examine how a protein motif originally capable of one function can be adapted to perform other functions in the cell. The project is also designed to integrate research with training of undergraduate and graduate students who will gain hands-on experience in designing, executing, and interpreting experiments. In addition, a postdoctoral fellow who is planning a career in undergraduate education will gain teaching experience by coaching undergraduates in the laboratory, developing and implementing assessments for an undergraduate laboratory course, and designing and teaching a course during the three-week winter session. Finally, this project will enhance genetic resources for model organisms by developing additional yeast species for comparative evolutionary studies.The fates of duplicate genes are well-modeled theoretically. However, few studies of gene duplication move beyond sequence analysis to elucidate the changes that occur in protein function as duplicated genes diverge. The project will help fill this knowledge gap by tracing the evolution of two proteins that arose from subunits of the origin recognition complex (ORC). ORC promotes the assembly of a pre-replication complex for DNA synthesis, and five of its six subunits contain AAA+ domains that bind and hydrolyze ATP. In the budding yeast lineage, Orc1 duplicated to yield the heterochromatin protein Sir3, and Orc4 gave rise to the telomere-binding protein Rif2. Both Sir3 and Rif2 lack ATPase activity and have repurposed the AAA+ domain to bind other proteins. The research will compare the molecular properties of Orc1/Sir3 and Orc4/Rif2 in non-duplicated and duplicated yeast species, focusing on their protein interactions and genomic distributions. In addition, the contributions of these proteins to transcriptional repression and telomere length regulation will be examined. The findings will illustrate and clarify theoretical models of gene duplication by identifying how and when new protein functions arise.