Nuclear genetic background influences the phenotype of the Drosophila tko25t mitochondrial protein-synthesis mutant

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    Abstract

    The Drosophila tko25t point mutation in the gene encoding mitoribosomal protein S12 produces a complex phenotype of multiple respiratory chain deficiency, developmental delay, bang-sensitivity, impaired hearing, sugar and antibiotic sensitivity, and impaired male courtship. Its phenotypic severity was previously shown to be alleviated by inbreeding and to vary with mitochondrial genetic background. Here, we show similarly profound effects conferred by nuclear genetic background. We backcrossed tko25t into each of 2 standard nuclear backgrounds, Oregon R and w1118, the latter used as recipient line in many transgenic applications requiring selection for the white minigene marker. In the w1118 background, tko25t flies showed a moderate developmental delay and modest bang-sensitivity. In the Oregon R background, males showed longer developmental delay and more severe bang-sensitivity, and we were initially unable to produce homozygous tko25t females in sufficient numbers to conduct a meaningful analysis. When maintained as a balanced stock over 2 years, tko25t flies in the Oregon R background showed clear phenotypic improvement though were still more severely affected than in the w1118 background. Phenotypic severity did not correlate with the expression level of the tko gene. Analysis of tko25t hybrids between the 2 backgrounds indicated that phenotypic severity was conferred by autosomal, X-chromosomal, and parent-of-origin-dependent determinants. Although some of these effects may be tko25t specific, we recommend that, in order to minimize genetic drift and confounding background effects, the genetic background of nonlethal mutants should be controlled by regular backcrossing, even if stocks are usually maintained over a balancer chromosome.

    Original languageEnglish
    Article numberjkad078
    JournalG3: Genes, Genomes, Genetics
    Volume13
    Issue number6
    DOIs
    Publication statusPublished - Jun 2023
    Publication typeA1 Journal article-refereed

    Funding

    HTJ was supported in this work by grants from the Academy of Finland (283157, 307431, and 324730). We thank Lotta Kulmala and Eveliina Teeri-Kahelin for their technical assistance. The work was conducted with practical support from the Biocenter Finland-funded Tampere Drosophila Facility.

    Keywords

    • mitochondria
    • nuclear background
    • ribosome
    • semilethality

    Publication forum classification

    • Publication forum level 2

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Genetics(clinical)

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