4.8 Article

Interplay Between Polymorphic Short Tandem Repeats and Gene Expression Variation in Caenorhabditis elegans

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MOLECULAR BIOLOGY AND EVOLUTION
卷 40, 期 4, 页码 -

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OXFORD UNIV PRESS
DOI: 10.1093/molbev/msad067

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short tandem repeats; gene regulation; expression QTL; oxidative stress; antioxidant genes; Caenorhabditis elegans

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This study conducted a genome-wide analysis using expression and short tandem repeat (STR) variation data from wild Caenorhabditis elegans strains, and identified expression STRs (eSTRs) that have regulatory effects on gene expression variation. The study revealed specific regulatory mechanisms of eSTRs, such as their effects on splicing sites and alternative splicing efficiency. It also demonstrated that differential expression of antioxidant genes and oxidative stresses can contribute to higher mutation rates of STRs.
Short tandem repeats (STRs) have orders of magnitude higher mutation rates than single nucleotide variants (SNVs) and have been proposed to accelerate evolution in many organisms. However, only few studies have addressed the impact of STR variation on phenotypic variation at both the organismal and molecular levels. Potential driving forces underlying the high mutation rates of STRs also remain largely unknown. Here, we leverage the recently generated expression and STR variation data among wild Caenorhabditis elegans strains to conduct a genome-wide analysis of how STRs affect gene expression variation. We identify thousands of expression STRs (eSTRs) showing regulatory effects and demonstrate that they explain missing heritability beyond SNV-based expression quantitative trait loci. We illustrate specific regulatory mechanisms such as how eSTRs affect splicing sites and alternative splicing efficiency. We also show that differential expression of antioxidant genes and oxidative stresses might affect STR mutations systematically using both wild strains and mutation accumulation lines. Overall, we reveal the interplay between STRs and gene expression variation by providing novel insights into regulatory mechanisms of STRs and highlighting that oxidative stress could lead to higher STR mutation rates.

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