Natural variation inC. elegansshort tandem repeats

Abstract

Short tandem repeats (STRs) represent an important class of genetic variation that can contribute to phenotypic differences. Although millions of single nucleotide variants (SNVs) and short indels have been identified among wild Caenorhabditis elegans strains, the natural diversity in STRs remains unknown. Here, we characterized the distribution of 31,991 STRs with motif lengths of 1-6 bp in the reference genome of C. elegans. Of these STRs, 27,667 harbored polymorphisms across 540 wild strains and only 9,691 polymorphic STRs (pSTRs) had complete genotype data for more than 90% of the strains. Compared to the reference genome, the pSTRs showed more contraction than expansion. We found that STRs with different motif lengths were enriched in different genomic features, among which coding regions showed the lowest STR diversity and constrained STR mutations. STR diversity also showed similar genetic divergence and selection signatures among wild strains as in previous studies using single-nucleotide variants. We further identified STR variation in two mutation accumulation line panels that were derived from two wild strains and found background-dependent and fitness-dependent STR mutations. We also performed the first genome-wide association analyses between natural variation in STRs and organismal phenotypic variation among wild C. elegans strains. Overall, our results delineate the first large-scale characterization of STR variation in wild C. elegans strains and highlight the effects of selection on STR mutations.

Variation in mutational (co)variances

“…3a ), our result is consistent with the observation that N2 and PB306 genotypes show similar mutation rates and molecular spectra for single nucleotide polymorphisms ( Denver et al 2012 ; Rajaei et al 2021 ). However, a more recent study with an extensive set of MA lines from both genotypes has indicated that mutation rates for short-tandem repeats (STRs) were different ( Zhang et al 2022 ). Given that some of these STRs have also been shown to affect QTL for polygenic traits ( Zhang et al 2022 ), one could have expected that the two M matrices for locomotion behavior would be different.…”

“…However, a more recent study with an extensive set of MA lines from both genotypes has indicated that mutation rates for short-tandem repeats (STRs) were different ( Zhang et al 2022 ). Given that some of these STRs have also been shown to affect QTL for polygenic traits ( Zhang et al 2022 ), one could have expected that the two M matrices for locomotion behavior would be different. Regarding M matrix orientation, it should depend on pleiotropy and therefore on the amount of genetic covariances between transition rates ( Lande 1980 ; Phillips and McGuigan 2006 ).…”

A nematode model to evaluate microdeletion phenotype expression

“…No obvious homology is observed around the breakpoints of the sprDf1 allele, suggesting that the microdeletion allele may not have arisen by this classic mechanism. However, extended microsatellite repeat sequences are located within a few hundred base pairs of both breakpoint sites [54]. An extended octonucleotide repeat sequence ATGCCTAC is found in 27 copies upstream of the left breakpoint, and 26 copies of a hexanucleotide repeat sequence CTAAGC are found upstream of the right breakpoint.…”

SUMO protease FUG1, histone reader AL3 and the PRC1 Complex are integral to repeat-expansion induced epigenetic silencing inArabidopsis thaliana

“…Variation in the length of short tandem repeats is associated with diverse phenotypic changes across organisms [6][7][8][9][10][11] . In humans, extreme length variants exemplified by repeat expansions cause several diseases such as Huntington's disease and Friedreich's ataxia 8,12 .…”

“…AL3 physically interacts with LHP1 of the PRC1 complex and the FUG1-AL3-LHP1 module is essential to confer repeat expansion-associated epigenetic silencing. Our findings highlight the importance post-translational modifiers and histone readers in epigenetic silencing caused by repeat expansions.Variation in the length of short tandem repeats is associated with diverse phenotypic changes across organisms [6][7][8][9][10][11] . In humans, extreme length variants exemplified by repeat expansions cause several diseases such as Huntington's disease and Friedreich's ataxia 8,12 .…”