Mapping QTL, epistasis and genotype × environment interaction of antioxidant activity, chlorophyll content and head formation in domesticated lettuce (Lactuca sativa).

Fruits and vegetables are rich sources of antioxidants in human diets and their intake is associated with chronic disease prevention. Lettuce (Lactuca sativa L.) is a common vegetable in diets worldwide, but its nutritional content is relatively low. To elucidate the genetic basis of antioxidant content in lettuce, we measured the oxygen radical absorbance capacity (ORAC) and chlorophyll (Chl) content as a proxy of ß-carotene in an F(8) recombinant inbred line (RIL) in multiple production cycles at two different production sites. Plants were phenotyped at the open-leaf stage to measure genetic potential (GP) or at market maturity (MM) to measure the influence of head architecture ('head' or 'open'). Main effect quantitative trait loci (QTL) were identified at MM (three Chl and one ORAC QTL) and GP (two ORAC QTL). No main effect QTL for Chl was detected at GP, but epistatic interaction was identified in one pair of marker intervals for each trait at GP. Interactions with environment were also detected for both main and epistatic effects (two for main effect, and one for epistatic effect). Main effect QTL for plant architecture and nutritional traits at MM colocated to a single genomic region. Chlorophyll contents and ORAC values at MM were significantly higher and Chl a to Chl b ratios were lower in 'open' types compared to 'head' types. The nutritional traits assessed for GP showed a significant association with plant architecture suggesting pleiotropic effects or closely linked genes. Taken together, the antioxidant and chlorophyll content of lettuce is controlled by complex mechanisms and participating alleles change depending on growth stage and production environment.

The cystic-fibrosis-associated ΔF508 mutation confers post-transcriptional destabilization on the C. elegans ABC transporter PGP-3.

Membrane proteins make up ∼30% of the proteome. During the early stages of maturation, this class of proteins can experience localized misfolding in distinct cellular compartments, such as the cytoplasm, endoplasmic reticulum (ER) lumen and ER membrane. ER quality control (ERQC) mechanisms monitor folding and determine whether a membrane protein is appropriately folded or is misfolded and warrants degradation. ERQC plays crucial roles in human diseases, such as cystic fibrosis, in which deletion of a single amino acid (F508) results in the misfolding and degradation of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. We introduced the ΔF508 mutation into Caenorhabditis elegans PGP-3, a 12-transmembrane ABC transporter with 15% identity to CFTR. When expressed in intestinal epithelial cells, PGP-3(wt) was stable and efficiently trafficked to the apical plasma membrane through a COPII-dependent mechanism. However, PGP-3(ΔF508) was post-transcriptionally destabilized, resulting in reduced total and apical membrane protein levels. Genetic or physiological activation of the osmotic stress response pathway, which causes accumulation of the chemical chaperone glycerol, stabilized PGP-3(ΔF508). Efficient degradation of PGP-3(ΔF508) required the function of several C. elegans ER-associated degradation (ERAD) homologs, suggesting that destabilization occurs through an ERAD-type mechanism. Our studies show that the ΔF508 mutation causes post-transcriptional destabilization and degradation of PGP-3 in C. elegans epithelial cells. This model, combined with the power of C. elegans genetics, provides a new opportunity to genetically dissect metazoan ERQC.