Correlated Evolution of the Skeletal System in Mice Selectively Bred for Longer Tibiae

Unger, Colton Michael

Correlated Evolution of the Skeletal System in Mice Selectively Bred for Longer Tibiae

dc.contributor.advisor	Rolian, Campbell
dc.contributor.advisor	Cobb, John
dc.contributor.author	Unger, Colton Michael
dc.contributor.committeemember	Hallgrimsson, Benedikt
dc.contributor.committeemember	Jamniczky, Heather
dc.contributor.committeemember	Young, Nathan
dc.contributor.committeemember	Biernaskie, Jeff
dc.date	2024-11
dc.date.accessioned	2024-07-15T16:05:58Z
dc.date.available	2024-07-15T16:05:58Z
dc.date.issued	2024-07-10
dc.description.abstract	Organisms are complex systems of traits, which grow together and influence each other during development, leading to covariation among anatomical structures. Underlying genetic and developmental correlations between traits can influence evolutionary trajectories, and may lead to indirect, non-adaptive, or mal-adaptive responses to selection in a process called correlated evolution. Thus, distinct traits that are developmentally or functionally related are unlikely to evolve independently, and selection can result in off-target phenotypic change. Skeletal tissues tend to covary significantly in length and shape due to their shared functional role (e.g., locomotion) and shared mechanism of development, known as endochondral ossification (EO). Together, these features of mammalian skeletal tissues lead to strong covariation between skeletal elements, such as limb bones, vertebrae, and to a lesser extent, the cranial bones. The mechanism of EO in bone development is also reinitiated during the repair of long bone fractures. Therefore, there is great potential for correlated responses to selection in skeletal traits, potentially leading to correlated phenotypic changes when a given skeletal trait is under direct selection. To study correlated evolution in skeletal traits, I used the Longshanks mouse, which was selectively bred for increases in adult tibia length independent of body mass, resulting in 15-20% longer tibiae than Controls due to increased rates of EO during development. Using bone imaging, geometric morphometrics, histomorphometry, and transcriptomics, I characterized potential correlated changes to other traits in Longshanks that utilize the program of EO, including other off-target long bones, the cranium, and the repair of bone fractures. Using this multifaceted approach, I demonstrated that the cranium and postcranial skeleton of Longshanks have differentially elongated during the selection process, which coincided with changes to gene expression and chondrocyte behavior that resembled documented trends in the tibia. In doing so, I identified molecular and cellular signatures underlying skeletal trait correlations and identified pathways contributing to the local and global scaling of skeletal traits. Moreover, I demonstrated that Longshanks repairs unstabilized tibia fractures faster than Controls without compromising bone quality, owing to an accelerated EO phase of repair at the genetic and tissue levels. Together, this work provides strong empirical evidence of correlated trait evolution and furthers our understanding of how covariation shapes evolutionary trajectories at the microevolutionary scale, with implications for understanding morphological divergence in skeletal form and function.
dc.identifier.citation	Unger, C. M. (2024). Correlated evolution of the skeletal system in mice selectively bred for longer tibiae (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/119182
dc.language.iso	en
dc.publisher.faculty	Science
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Evolutionary Developmental Biology
dc.subject	Limb Development
dc.subject	Skeletal Development
dc.subject	Correlated Evolution
dc.subject	Artificial Selection
dc.subject.classification	Education--Sciences
dc.subject.classification	Anatomy
dc.subject.classification	Genetics
dc.subject.classification	Biology--Cell
dc.subject.classification	Biology--Molecular
dc.title	Correlated Evolution of the Skeletal System in Mice Selectively Bred for Longer Tibiae
dc.type	doctoral thesis
thesis.degree.discipline	Biological Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.