In the Bateson-Dobzhansky-Muller (BDM) model of speciation, incompatibilities emerge from the deleterious interactions between alleles that are neutral or advantageous in the original genetic backgrounds, i.e., negative epistatic effects. Within species such interactions are responsible for outbreeding depression and F2 (hybrid) breakdown. We sought to identify BDM incompatibilities in the nematode Caenorhabditis elegans by looking for genomic regions that disrupt egg laying; a complex, highly regulated, and coordinated phenotype. Investigation of introgression lines and recombinant inbred lines derived from the isolates CB4856 and N2 uncovered multiple incompatibility quantitative trait loci (QTL). These QTL produce a synthetic egg-laying defective phenotype not seen in CB4856 and N2 nor in other wild isolates. For two of the QTL regions, results are inconsistent with a model of pairwise interaction between two loci, suggesting that the incompatibilities are a consequence of complex interactions between multiple loci. Analysis of additional life history traits indicates that the QTL regions identified in these screens are associated with effects on other traits such as lifespan and reproduction, suggesting that the incompatibilities are likely to be deleterious. Taken together, these results indicate that numerous BDM incompatibilities that could contribute to reproductive isolation can be detected and mapped within C. elegans.

Most ectotherms obey the temperature-size rule, meaning they grow larger in a colder environment. This raises the question of how the interplay between genes and temperature affect the body size of ectotherms. Despite the growing body of literature on the physiological life-history and molecular genetic mechanism underlying the temperature-size rule, the overall genetic architecture orchestrating this complex phenotype is not yet fully understood. One approach to identify genetic regulators of complex phenotypes is Quantitative Trait Locus (QTL) mapping. Here, we explore the genetic architecture of body size phenotypes, in different temperatures using Caenorhabditis elegans as a model ectotherm. We used 40 recombinant inbred lines (RILs) derived from N2 and CB4856, which were reared at four different temperatures (16°C, 20°C, 24°C, and 26°C) and measured at two developmental stages (L4 and adult). The animals were measured for body length, width at vulva, body volume, length/width ratio, and seven other body-size traits. The genetically diverse RILs varied in their body-size phenotypes with heritabilities ranging from 0.20 to 0.99. We detected 18 QTL underlying the body-size phenotypes across all treatment combinations, with the majority clustering on Chromosome X. We hypothesize that the Chromosome X QTL could result from a known pleiotropic regulator – npr-1 – known to affect the body size of C. elegans through behavioral changes. In conclusion, our findings shed more light on multiple loci affecting body size plasticity and allow for a more refined analysis of the temperature-size rule.

Accumulation of protein aggregates is a major cause of Parkinson's disease (PD), a progressive neurodegenerative condition that is one of the most common causes of dementia. Transgenic Caenorhabditis elegans worms expressing the human synaptic protein α-synuclein show inclusions of aggregated protein and replicate the defining pathological hallmarks of PD. It is however not known how PD progression and pathology differs among individual genetic backgrounds. Here, we compared gene expression patterns, and investigated the phenotypic consequences of transgenic α-synuclein expression in five different C. elegans genetic backgrounds. Transcriptome analysis indicates that the effects of α-synuclein expression on pathways associated with nutrient storage, lipid transportation and ion exchange depend on the genetic background. The gene expression changes we observe suggest that a range of phenotypes will be affected by α-synuclein expression. We experimentally confirm this, showing that the transgenic lines generally show delayed development, reduced lifespan, and an increased rate of matricidal hatching. These phenotypic effects coincide with the core changes in gene expression, linking developmental arrest, mobility, metabolic and cellular repair mechanisms to α-synuclein expression.Together, our results show both genotype-specific effects and core alterations in global gene expression and in phenotype in response to α-synuclein. We conclude that the PD effects are substantially modified by the genetic background, illustrating that genetic background mechanisms should be elucidated to understand individual variation in PD.