Natural variation in C. elegans short tandem repeats

Area of Science:

• Genetics
• Evolutionary Biology
• Genomics

Background:

• Short tandem repeats (STRs) are a key source of genetic variation influencing phenotypes.
• While single nucleotide variants (SNVs) and indels in wild Caenorhabditis elegans are well-studied, natural STR diversity remains largely unknown.

Purpose of the Study:

• To characterize the distribution and diversity of STRs in wild Caenorhabditis elegans strains.
• To investigate the impact of selection on STR variation and its relationship with genomic features and phenotypes.

Main Methods:

• Genome-wide characterization of 31,991 STRs in the C. elegans reference genome.
• Genotyping of 540 wild strains to identify polymorphic STRs (pSTRs).
• Analysis of STR variation in mutation accumulation lines and genome-wide association studies.

Main Results:

• Identified 9,691 pSTRs with comprehensive genotype data across wild strains.
• Observed more STR contraction than expansion compared to the reference genome.
• Found STR diversity patterns consistent with genetic divergence and selection signatures seen for SNVs.
• STRs in coding regions exhibited lower diversity and constrained mutations.
• Discovered background-dependent and fitness-dependent STR mutations in accumulation lines.
• Performed the first genome-wide association analyses linking STR variation to organismal phenotypes.

Conclusions:

• This study provides the first large-scale characterization of STR variation in wild C. elegans.
• STR diversity is influenced by selection, with distinct patterns across different motif lengths and genomic features.
• STRs contribute to phenotypic variation and are subject to evolutionary forces in natural populations.