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Analysis of Regulatory Elements in Canine Genomes
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
2024 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesisAlternative title
Analys av regulatoriska element i hundgenom (Swedish)
Abstract [sv]

Hundar utvecklades från gråvargar för mer än 15 000 år sedan och uppvisar distinkta fenotypiska egenskaper som särskiljer dem från sina vargförfäder. Trots att majoriteten av forskningen kring genetiska mekanismer för evolution har fokuserat på proteinkodade gener, kan funktionella mutationer lokaliseras i regulatoriska regioner. För att undersöka de reglerande mekanismer som ligger bakom dessa förändringar analyserades RNA-sekvensering (RNA-seq) och Capture Hi-C (HiCap) för att studera genuttryck och kromatininteraktioner i hypotalamus och prefrontala cortex hos hundar och vargar. RNA-seq-analysen identifierade 12 024 uttrycka gener, inklusive 353 differentiellt uttryckta gener (DEG) i hypotalamus och 931 i prefrontala cortex. Analysen av HiCap-interaktioner avslöjade signifikanta promotor-distal-interaktioner, vilket tyder på att förstärkare spelar en nyckelroll i genreglering. Genontologi (GO) termanrikningsanalys indikerade en nedreglering hos hundar med avseende på de biologiska processerna relaterade till minne, inlärning, neurogenes och kognitiva funktioner. Dessa fynd ger insikter i de reglerade elementen som drivkrafter för evolutionär divergens hos hundar och vargar, vilket understryker vikten av icke-kodande regioner i domesticering.

Abstract [en]

Dogs evolved from grey wolves at least 15,000 years ago, and exhibit distinct phenotypic traits that sets them apart from their wolf ancestors. While most research on genetic mechanisms of evolution have been focused on protein coding genes, functional mutations could be located in regulatory regions. To investigate the regulatory mechanisms underlying these changes, RNA sequencing (RNA-seq) and Capture Hi-C (HiCap) were analyzed to study gene expression and chromatin interactions in the hypothalamus and prefrontal cortex of dogs and wolves. The RNA seq analysis identified 12,024 expressed genes, including 353 differentially expressed genes (DEGs) in the hypothalamus and 931 in the prefrontal cortex. The analysis of HiCap interactions revealed significant promoter-distal interactions, suggesting that enhancers play a key role in gene regulation. Gene ontology (GO) term enrichment analysis indicated a downregulation in dogs for the biological processes related to memory, learning, neurogenesis and cognitive functions. These findings provide insights into the regulatory elements as drivers of evolutionary divergence of dogs and wolves which emphasizes the importance of non-coding regions in domestication.

Place, publisher, year, edition, pages
2024.
Series
TRITA-CBH-GRU ; 2024:380
Keywords [en]
Capture Hi-C, RNA sequencing, enhancers, evolution
Keywords [sv]
Capture Hi-C, RNA-sekvensering, förstärkare, evolution
National Category
Genetics and Genomics
Identifiers
URN: urn:nbn:se:kth:diva-356608OAI: oai:DiVA.org:kth-356608DiVA, id: diva2:1914636
Subject / course
Biotechnology
Educational program
Master of Science - Medical Biotechnology
Supervisors
Examiners
Available from: 2024-11-20 Created: 2024-11-20 Last updated: 2025-02-07

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