Salomon, Matthew et al. (2009) International Worm Meeting "Persistence time of mutations affecting fitness and body size in Caenorhabditis briggsae and C. elegans."

Upadhyay, Ambuj, Salomon, Matthew, Baer, Charles, Levy, Laura, Keller, Thomas, Phillips, Naomi, Blanton, Dustin, Ostrow, Dejerianne, Bour, Whitney, Sylvestre, Thamar

[International Worm Meeting, 2009]

The level of genetic variation present in a population is a composite function of mutation, population size, and natural selection. Historically, efforts to understand differences (or similarities) between groups in levels of genetic variation have focused on the interplay between population size and natural selection. However, much less attention has been paid to the alternative possibility that differences among groups are due to systematic differences in the underlying rate of mutation. Much of the difficulty in interpreting the role of mutation stems from the fact that most of what is known about genomic mutational properties, for quantitative traits in multicellular eukaryotes, comes from a handful of phylogenetically distant and biologically dissimilar model organisms, making meaningful comparisons difficult. Over the past several years our lab has been investigating the properties of new mutations in a model nematode system within a comparative phylogenetic framework. Mutations have been allowed to accumulate in the (relative) absence of natural selection, thus allowing us to estimate the genetic variance introduced by new mutation (VM) for two species of rhabditid nematodes, Caenorhabditis elegans and C. briggsae. Previous work in this system suggests that the mutation rate in C. briggsae is on the order of twice that of C. elegans for quantitative traits and dinucleotide repeats. Here we report the standing genetic variance (VG) for two quantitative traits, lifetime reproduction and body size, in worldwide collections of C. briggsae and C. elegans natural isolates. Comparisons of VG to VM between the natural isolates and our mutation accumulation lines allow us to infer the magnitude and pattern of constraint on phenotypic evolution in these two species. Taking the results from the two species together, the persistence time (VG/VM) of new mutations affecting fitness is on the order of tens to perhaps hundreds of generations, with an average selection coefficient against homozygotes of a few per-cent. Furthermore, the pattern of persistence time for mutations affecting adult body size is onsistent with that of fitness in both species. These results suggest that idiosyncratic selection, perhaps due to random hitchhiking - "genetic draft" - is paramount in shaping the standing genetic variance of these traits in these species.

Vediyappan G et al. (2013) PLoS One "Gymnemic acids inhibit hyphal growth and virulence in Candida albicans."

Pelissier F, d'Enfert C, Vediyappan G, Dumontet V

[PLoS One, 2013]

Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine.