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ABSTRACT Increased parental relatedness occurs in small wild populations and in closed colonies in captivity and reduces offspring fitness. A closed colony ofPeromyscus maniculatusis maintained as genetically diverse stock at the Peromyscus Genetic Stock Center since 1963. Breeding records are available for all the years of breeding in captivity, which allows evaluation of the breeding performance since the inception of the stock. Kinship calculations showed that increased parental relatedness results in offspring loss, which is consistent with the operation of inbreeding depression and is common in small populations, both wild and captive. Nonetheless, an adaptive response was recorded that mitigated the adverse consequences of inbreeding and contributed to the long‐term stability of the colony: When parental relatedness increased, more offspring were produced, resulting in the overall number of viable offspring being unaffected. The underlying mechanism involved adjustments in the interval for mating between related parents, causing the production of more litters. These adaptive changes indicate that the harmful consequences of inbreeding may be partially relieved by mechanisms involving changes in the animals' reproductive strategy. The availability of the breeding records ofP. maniculatusenables the performance of additional studies asking different questions regarding the breeding dynamics of a closed colony under regulated conditions. 

Abstract DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how stress factors impact aging. Deer mice (Peromyscus) are long-living rodents that have emerged as an informative model to study aging, adaptation to extreme environments, and monogamous behavior. In the present study, we have undertaken an exhaustive, genome-wide analysis of DNA methylation inPeromyscus, spanning different species, stocks, sexes, tissues, and age cohorts. We describe DNA methylation-based estimators of age for different species of deer mice based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for deer mice was trained on 3 tissues (tail, liver, and brain). Two human-Peromyscusclocks accurately measure age and relative age, respectively. We present CpGs and enriched pathways that relate to different conditions such as chronological age, high altitude, and monogamous behavior. Overall, this study provides a first step towards studying the epigenetic correlates of monogamous behavior and adaptation to high altitude inPeromyscus. The human-Peromyscusepigenetic clocks are expected to provide a significant boost to the attractiveness ofPeromyscusas a biological model. 

Historical reasons resulted in the almost exclusive use of a few species, most prominently Mus musculus, as the mainstream models in biomedical research. This selection was not based on Mus’s distinctive relevance to human disease but rather to the pre-existing availability of resources and tools for the species that were used as models, which has enabled their adoption for research in health sciences. Unless the utilization and range of nontraditional research models expand considerably, progress in biomedical research will remain restricted within the trajectory that has been set by the existing models and their ability to provide clinically relevant information.