Braeckman, B. P. | Search bioRxiv

bioRxiv2018

A multi-parent recombinant inbred line population of Caenorhabditis elegans enhances mapping resolution and identification of novel QTLs for complex life-history traits

Local populations of the bacterivorous nematode Caenorhabditis elegans can be genetically almost as diverse as global populations. To investigate the effect of local genetic variation on heritable traits, we developed a new recombinant inbred line (RIL) population derived from four wild isolates. The wild isolates were collected from two closely located sites in France: Orsay and Santeuil. By crossing these four genetically diverse parental isolates a population of 200 RILs was constructed. RNA-seq was used to obtain sequence polymorphisms identifying almost 9000 SNPs variable between the four genotypes with an average spacing of 11 kb, possibly doubling the mapping resolution relative to currently available RIL panels. The SNPs were used to construct a genetic map to facilitate QTL analysis. Life history traits, such as lifespan, stress resistance, developmental speed and population growth were measured in different environments. For most traits substantial variation was found, and multiple QTLs could be detected, including novel QTLs not found in previous QTL analysis, for example for lifespan or pathogen responses. This shows that recombining genetic variation across C. elegans populations that are in geographical close proximity provides ample variation for QTL mapping. Taken together, we show that RNA-seq can be used for genotyping, that using more parents than the classical two parental genotypes to construct a RIL population facilitates the detection of QTLs and that the use of wild isolates permits analysis of local adaptation and life history trade-offs.

genetics↗

bioRxiv2018

Royalactin induces copious longevity via increased translation and proteasome activity in C. elegans.

As demonstrated in various animal models, organismal longevity can be achieved via interventions that at the mechanistic level could be considered to entail defensive responses: most long-lived mutants focus on somatic maintenance, while reducing growth pathway signalling and protein translation and turnover. We here provide evidence that the opposite mechanism can also lead to longevity and improved health.\n\nWe report on the mode of action of royalactin, a glycoprotein activator of epidermal growth factor signalling, capable of extending lifespan in several animals. We show that in Caenorhabditis elegans, royalactin-induced longevity depends on increased protein translation and entails increased proteasome activity. We propose the term copious longevity to describe this newly-elucidated mechanism. In contrast to what is true for many other lifespan-extending interventions, we observed no obvious trade-offs between royalactin-induced longevity and several life history traits. Our data point towards increased protein turnover to support healthy ageing, and provide a means for future comparative studies of defensive vs. copious mechanisms.

molecular biology↗