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

Area of Science:

• Genetics and Genomics
• Evolutionary Biology
• Molecular Biology

Background:

• Short tandem repeats (STRs) exhibit higher mutation rates than single nucleotide variants (SNVs), suggesting a role in evolution.
• The impact of STR variation on organismal and molecular phenotypes remains understudied.
• The underlying causes of high STR mutation rates are largely unknown.

Purpose of the Study:

• To investigate the genome-wide impact of STR variation on gene expression in wild Caenorhabditis elegans strains.
• To identify regulatory mechanisms by which STRs influence gene expression.
• To explore the relationship between oxidative stress and STR mutation rates.

Main Methods:

• Genome-wide analysis of STR and gene expression variation in wild Caenorhabditis elegans.
• Identification of expression STRs (eSTRs) and their regulatory effects.
• Analysis of mutation accumulation lines and wild strains to assess the role of oxidative stress.

Main Results:

• Thousands of eSTRs were identified, demonstrating significant regulatory effects on gene expression.
• eSTRs explained substantial missing heritability not accounted for by SNV-based expression quantitative trait loci (eQTLs).
• STRs were shown to influence splicing sites and alternative splicing efficiency.
• Differential expression of antioxidant genes and oxidative stress were linked to systematic STR mutations.

Conclusions:

• STRs play a crucial role in gene expression variation, offering insights into regulatory mechanisms.
• eSTRs contribute significantly to heritability, highlighting their importance beyond SNVs.
• Oxidative stress emerges as a potential driver of increased STR mutation rates, impacting evolutionary processes.