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dc.contributor.advisorElinor Karlssonen_US
dc.contributor.authorLi, Xue
dc.date.accessioned2023-05-25T14:25:25Z
dc.date.available2023-05-25T14:25:25Z
dc.date.issued2023-05-05
dc.identifier.doi10.13028/29eh-xt35en_US
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52121
dc.description.abstractDomesticated dogs separated from wolves around ~5000-7000 generations ago, with major differences in early social development that have enabled them to survive, and thrive, in close proximity to humans. Due to their unique evolutionary history and accessibility, canines serve as a natural model system to study the genetic factors underlying behavior adaptation within and between subspecies. The wolf/dog system can not only advance the understanding of evolutionary processes, but also help to better understand the neurogenetic pathways involved in human psychiatric disorders. Although wolves and dogs split relatively recently in evolutionary time, they are genetically distinct populations with numerous differences across their genome. This population structure makes it impossible to confidently associate particular genomic variants with domestication-related traits by simply comparing dogs and wolves. In this dissertation, I identified genes and pathways associated with domestication-related behavior using an unusual admixed population of wolf-dog hybrids housed in sanctuaries across the United States. I developed methods and approaches to map behavioral phenotypes in wolf-dog hybrids, and explored the overlap with dog social behaviors, and human psychiatric conditions. I first characterized the population history of wolf-dog hybrids using techniques including exploratory principal component analysis, ancestry calling, and population differentiation test. I defined the behavioral phenotypes by dimensional reduction analysis of coded video data, and identified associations between genes and regulatory elements with those phenotypes using admixture mapping and association test. Finally, I investigated the functional and biological mechanisms underlying the associated regions by gene-set analysis. I discovered that regions associated with domestication-related behavioral differences are enriched for brain expressed genes, especially those enriched in early infancy. To further investigate the candidate regions associated with canine domestication, I leveraged a powerful new data resource comparing the genomes of 240 mammalian species. Using data from massively parallel reporter assay experiments in human cells, I confirmed that this resource can distinguish which bases have regulatory function. Overall, variants in highly constrained positions are more likely to alter cellular function. In addition, I showed that dogs with ancestry from a single breed, which have shorter lifespans than outbred dogs, are also more likely to carry variants in constrained positions, suggesting they impact fitness. In the wolf-dog hybrids, I cataloged candidate causal variants that differed between dogs and wolves and were highly constrained across mammals. Overall, this thesis demonstrates how new genomic tools and data resources can be leveraged to investigate exceptional evolutionary adaptations in other species that may offer insight into human diseases. By utilizing the wolf-dog hybrid population, we can re-trace the ancient genetic changes of domestication that led to divergence of canine social and developmental behaviors, and potentially uncover genetic pathways that contribute to social behavioral disorders such as autism spectrum disorders.en_US
dc.language.isoen_USen_US
dc.publisherUMass Chan Medical Schoolen_US
dc.rightsCopyright © 2023 Xue (Shirley) Lien_US
dc.rights.uriAll Rights Reserveden_US
dc.subjectSocial behaviorsen_US
dc.subjectWolf-dog hybridsen_US
dc.subjectDomesticationen_US
dc.subjectComparative genomicsen_US
dc.subjectAdmixture mappingen_US
dc.subjectNatural model systemen_US
dc.titleIntegrating evolution and genomics to investigate social development in wolf-dog hybridsen_US
dc.typeDoctoral Dissertationen_US
atmire.contributor.authoremailshirleyxueli41@gmail.comen_US
dc.contributor.departmentProgram in Bioinformatics and Integrative Biologyen_US
dc.description.thesisprogramBioinformatics and Computational Biologyen_US
dc.identifier.orcid0000-0002-9126-2692en_US


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