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Biology subjects

David Riccardi

Publications and source records attributed to David Riccardi.

2 recordsLinked to original sources

The genetic basis of natural variation in C. elegans telomere length

Telomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored. Here, we describe natural variation in telomere length across the Caenorhabditis elegans species. We identify a large-effect variant that contributes to differences in telomere length. The variant alters the conserved oligosaccharide/oligonucleotide-binding fold of POT-2, a homolog of a human telomere-capping shelterin complex subunit. Mutations within this domain likely reduce the ability of POT-2 to bind telomeric DNA, thereby increasing telomere length. We find that telomere-length variation does not correlate with offspring production or longevity in C. elegans wild isolates, suggesting that naturally long telomeres play a limited role in modifying fitness phenotypes in C. elegans.

Genetics

C. elegans harbors pervasive cryptic genetic variation for embryogenesis

Conditionally functional mutations are an important class of natural genetic variation, yet little is known about their prevalence in natural populations or their contribution to disease risk. Here, we describe a vast reserve of cryptic genetic variation, alleles that are normally silent but which affect phenotype when the function of other genes is perturbed, in the gene networks of C. elegans embryogenesis. We find evidence that cryptic-effect loci are ubiquitous and segregate at intermediate frequencies in the wild. The cryptic alleles demonstrate low developmental pleiotropy, in that specific, rather than general, perturbations are required to reveal them. Our findings underscore the importance of genetic background in characterizing gene function and provide a model for the expression of conditionally functional effects that may be fundamental in basic mechanisms of trait evolution and the genetic basis of disease susceptibility.

Evolutionary Biology