Date of Award

Summer 2025

Document Type

Open Access Dissertation

Department

College of Pharmacy

First Advisor

Hippokratis Kiaris

Abstract

Evolutionary success is defined by the ability of a species to adapt and survive across many generations. This success is not determined by any single attribute but rather includes the entrenched, complex system that could be associated with biological rhythms, reproductive strategies, and regulations of epigenetic and genetic components. By using closed Peromyscus colonies as a model and by coupling mathematical modeling, analyses of breeding records, epigenetic studies, and in vitro and in vivo experiments, this dissertation aims to discover how Peromyscus adjusts to the internal and external pressures to ensure their survival and preserve evolutionary fitness in controlled environments.

The first major finding of this dissertation is how Peromyscus can regulate the timing of their breeding, even inside an animal facility with controlled temperature and light exposure, in a manner that follows circannual rhythms. Specifically, over the span of more than 60 years, Peromyscus continues to breed in accordance with equinoxes, indicating that their biological architecture is hardwired to this specific periodic adaptation. Further exploration in the patterns of DNA methylation reveals that there are specific methylation signals that also follow a cyclic trend according to the birth season of the deer mice. Additionally, we reveal how monogamous mating systems improve reproductive consistency and resistance to seasonal cues. Monogamous Peromyscus pairs showed more stable methylation patterns in their offspring and less seasonal variation in reproductive output than their polygamous counterparts. These results imply that social structures and mating behaviors that protect young from environmental uncertainty, in addition to biological clocks, support a species' well-being.

We also unveiled an unexpected relationship between parental relatedness and epigenetic aging. Contrary to classical expectations of inbreeding depression, increased kinship between parents correlated with slower biological aging in offspring. These findings challenge traditional assumptions that inbreeding universally reduces fitness, pointing instead to a stabilizing effect of genetic similarity on DNA methylation, especially when the deleterious alleles that may account for the loss of offspring of related parents have been purged out of the population. This epigenetic buffering may serve as a protective mechanism, maintaining genomic integrity and promoting longevity in offspring born under close kinship. An epigenetic signature of relatedness was also described that predicts parental kinship by methylation analyses. Furthermore, long-term colony records reveal that despite the constraints of a closed population, reproductive output remains resilient through an adaptive compensatory mechanism.

Collectively, by unraveling the molecular underpinnings of seasonal breeding, monogamous stability, and relatedness-driven epigenetic buffering, this work challenges conventional views about common regulators of breeding seasonality, inbreeding depression, and highlights the evolutionary ingenuity of Peromyscus in maintaining reproductive health across generations. These insights extend beyond laboratory settings, offering broader implications for conservation strategies and the sustainable management of small, isolated populations.

Rights

© 2025, Kim Tuyen Huynh Dam

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