Doctoral Dissertation Research: Uncovering the regulatory landscape of myofiber type in the context of human evolution

University Of Oregon Eugene, Eugene OR

Investigators

Abstract

Humans are distinguished by their ability to walk upright on two legs and their capacity for endurance running. This behavior is explained in part by the endurance capabilities of human skeletal muscle, which, in comparison to chimpanzees, are better suited for holding bodies upright and being active for prolonged periods without fatiguing. However, it is unknown how this property of human skeletal muscle evolved due to its absence from the fossil record and a limited understanding of muscle fiber development at the genetic level. This doctoral dissertation project will identify the genetic switches controlling muscle fiber development using a suite of cutting-edge molecular methods. In doing so, this research will add novel information about the complex genetic landscape underlying muscle fiber development and illuminate the evolutionary history of a unique human trait that may have played a key role in bipedal evolution. This project will support graduate training in advanced molecular methods and bioinformatics. Additionally, the researcher will share their findings with the public by hosting a “science run” outreach event. Finally, data generated from this research will help characterize muscle biology at the genetic level and therefore has the potential to help target more efficient treatments for a range of neuromuscular diseases. Understanding when, why and how the transition to bipedalism occurred over the course of human evolution is a fundamental question in biological anthropology. As a species, humans are characterized by a suite of well-described anatomical adaptations that support efficient, long-distance bipedal locomotion. While many of these traits are observable in the fossil record (e.g., bone morphology), others (e.g., properties of skeletal muscle) are more difficult to detect. The high proportion of fatigue-resistant slow-twitch muscle fibers in human hind limb muscles optimizes them to perform tonic, endurance-based activities, and suggests that this trait helps enable long-distance bipedal locomotion. Yet, the genetic mechanisms controlling this trait are not well understood. To address this gap in knowledge, this project will identify the genetic mechanisms underlying muscle fiber development and reconstruct the evolutionary history of these mechanisms across primates. The central hypothesis of this research is that natural selection has selected for human-specific variation in regions of the genome that influence muscle fiber type, increasing the amount of slow-twitch fibers in human hind limb skeletal muscles and the efficiency of bipedal locomotion. To test this hypothesis, the researcher will first use a tailored ATACseq approach to identify those parts of the genome that are active in mammalian muscle tissues and associated with muscle fiber type. Next, they will test the function of a subset of these regions with human-specific variation. In doing so, this project will enrich anthropological understandings of human evolution by identifying regions of the human genome that have shaped the biology of a trait highly relevant to bipedalism. 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.