Comparative genomics and the evolution of immune genes in Drosophila
dc.contributor.advisor
Obbard, Darren
dc.contributor.advisor
Lohse, Konrad
dc.contributor.author
Dhakad, Pankaj
dc.date.accessioned
2025-11-07T13:18:58Z
dc.date.available
2025-11-07T13:18:58Z
dc.date.issued
2025-10-07
dc.description.abstract
Immune genes are among the most dynamic components of animal genomes, shaped by complex trade-offs between functional constraints, pathogen selective pressure, and environment. While Drosophila melanogaster has provided a detailed picture of innate immunity in insects, the family Drosophilidae—spanning over 60 million years and diverse ecological niches—offers a unique opportunity to study how immune systems evolve across deep evolutionary timescales. Recent large-scale sequencing efforts have now generated hundreds of high-quality drosophilid genomes, creating unprecedented opportunities for comparative analysis. However, a major limitation has been the lack of consistent gene annotations across species. In this thesis, I address this gap by generating standardized protein-coding gene annotations for 304 drosophilid species. Using a combination of comparative (CAT) and de novo (BRAKER3) annotation, guided by RNAseq and protein homology evidence, I built a consistent, high-quality gene annotation resource. I next investigated the evolutionary rates and turnover of immune-related genes relative to non-immune genes. Using models of DNA sequence evolution and trait evolution, I show that immune genes, particularly effectors and recognition proteins, evolve more rapidly than signaling genes and non-immune genes. I identified gene-level predictors of evolutionary rate, including expression level, relative solvent accessibility, gene length, and protein/genetic interactions. Finally, I used transcriptomic data from pathogen-challenged and unchallenged individuals of three non-model drosophilids to evaluate the bioinformatic recovery of known immune genes, to investigate their conservation and evolution of immune responses and discover novel immune effectors. I identified 20 candidate antimicrobial peptides that are infection-inducible, encode short, secreted proteins, and have no clear homologs in D. melanogaster, highlighting extensive lineage-specific evolution of immune effectors.
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dc.identifier.uri
https://hdl.handle.net/1842/44143
dc.identifier.uri
http://dx.doi.org/10.7488/era/6667
dc.language.iso
en
en
dc.publisher
The University of Edinburgh
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dc.relation.hasversion
Dhakad, P., B. Kim, D. Petrov and D. J. Obbard (2025a). ‘Comparative gene annotation of 304 species of Drosophilidae’. In: bioRxiv, p. 2025.04.14.648771. DOI: 10.1101/2025.04.14. 648771
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dc.relation.hasversion
Dhakad, P., D. Newman and D. J. Obbard (2025b). ‘Transcriptomic analysis of non-model Drosophilidae reveals novel AMP candidates’. In: bioRxiv, p. 2025.06.06.658223. DOI: 10. 1101/2025.06.06.658223
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dc.rights.license
Creative Commons: Attribution Non-Commercial 4.0 International (CC-BY-NC 4.0)
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dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
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dc.subject
Drosophila
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dc.subject
Comparative genomics
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dc.subject
Molecular evolution
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dc.subject
Immune genes
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dc.title
Comparative genomics and the evolution of immune genes in Drosophila
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dc.type
Thesis or Dissertation
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dc.type.qualificationlevel
Doctoral
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dc.type.qualificationname
PhD Doctor of Philosophy
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