Rebuilding a kinesin-based meiotic drive system from defined components

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This project aims to understand how some genes can be transmitted to progeny at higher frequencies than others. The flow of genetic information from parents to offspring is usually a fair process that allows genes from each parent to have an equal likelihood of being passed on. However, in some cases known as meiotic drive, genes cheat the system and have a higher likelihood of being passed on. A classic example of meiotic drive is found in maize, where a family of molecular motor proteins known as kinesins bind to specific chromosome regions and direct them to the egg cells. Work under this award is focused on two kinesin motor proteins known as Kindr and Trkin, which are similar, but cause meiotic drive at different chromosomal regions. Most of the experiments are designed to determine how the two kinesins bind to different regions. The ultimate aim is to engineer new kinesins that will bind to novel DNA sequences on chromosomes to test if they will show the same properties and cause meiotic drive. The project will integrate the research with education by engaging students at a predominantly undergraduate institutions in experiments to test the function of the maize kinesins in brewer's yeast. Together, the research outcomes will yield new insights into chromosome segregation, and in the long term, may allow researchers to control and improve the transmission of valuable traits.Kinesins function to move cargo within cells and organize spindles during mitosis and meiosis, where they help to ensure normal chromosome segregation. Two kinesins encoded on maize Abnormal chromosome 10 (Ab10), called Kindr and Trkin, are remarkable exceptions that evolved as selfish genes to favor their own segregation. To do this they have acquired the novel feature of binding to specialized repeat arrays called knobs and converting them into motile neocentromeres. Genetic evidence suggests that at least one of the kinesins (Kindr) does not bind directly, but through an intermediate factor tentatively called Smd13. A goal of this work is to identify Smd13 and understand how Kindr interacts with it to bind DNA. Other experiments are designed to understand how Trkin binds to DNA and interpret its role in meiotic drive. A final aim is to engineer new versions of Kindr and Trkin that bind to synthetic repeat arrays built into the maize genome and test whether the synthetic components promote meiotic drive. A yeast-based neocentromere system will also be developed to test whether kinesins can be used to move chromosome in a heterologous host. The results will expand our understanding of plant kinesins and their roles in meiosis and explore the utility of using kinesin-mediated chromosome movement to manipulate chromosome segregation.This award was jointly funded by the Genetics Mechanisms, Cellular Dynamics and Function, and Systems and Synthetic Biology Programs in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.