MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia

Inositol polyphosphates are vital metabolic and secondary messengers, involved in diverse cellular functions. Therefore, tight regulation of inositol polyphosphate metabolism is essential for proper cell physiology. Here, we describe an early-onset neurodegenerative syndrome caused by loss-of-function mutations in the multiple inositol-polyphosphate phosphatase 1 gene (MINPP1). Patients are found to have a distinct type of Pontocerebellar Hypoplasia with typical basal ganglia involvement on neuroimaging. We find that patient-derived and genome edited MINPP1−/− induced stem cells exhibit an inefficient neuronal differentiation combined with an increased cell death. MINPP1 deficiency results in an intracellular imbalance of the inositol polyphosphate metabolism. This metabolic defect is characterized by an accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions. These data suggest the involvement of IP6-mediated chelation on Pontocerebellar Hypoplasia disease pathology and thereby highlight the critical role of MINPP1 in the regulation of human brain development and homeostasis

Inferring native range and invasion scenarios with mitochondrial DNA : the case of T. solanivora successive north-south step-wise introductions across Central and South America

Tecia solanivora (Lepidoptera: Gelechiidae) is an invasive species that attacks the tubers of the potato Solanum tuberosum. It is considered a serious pest of potato crops and stocks in all countries where it occurs. In the present study, we sequenced 541 individuals sampled across the T. solanivora distribution range, using the mitochondrial DNA marker Cytochrome b (Cytb) to delimit the area of species origin. We also analyzed the genetic structure of T. solanivora in its putative area of origin and described differences in haplotype diversity between samples from different geographic origins affected by the invasion. We observed a gap in the level of genetic diversity between Guatemalan samples (h between 0.77 and 0.97) and those from Costa-Rica, Venezuela, Colombia, Ecuador and the Canary Islands (h between 0 and 0.56). The number of haplotypes has decreased over the colonization process, ending with the observation of a single haplotype in Colombia, Ecuador and the Canary Islands. Consequently, the invasion of South American countries by T. solanivora is likely to have had a front-like step-wise progression, where the most recently invaded country becomes the source of subsequent invasion

Reconstructing the invasion and the demographic history of the yellow-legged hornet, Vespa velutina, in Europe

The yellow-legged hornet, Vespa velutina, was accidentally introduced from Southeast Asia and then invaded France and Korea over the last 10 years. Since its introduction, its predation on honeybee colonies has rapidly become an economic problem in invaded countries. Using mitochondrial cytochrome C oxidase and 22 nuclear microsatellite loci, we showed that native hornet populations were well differentiated and highly diverse. In contrast, introduced populations from France and Korea suffered a genetic bottleneck, which did not prevent their rapid geographic expansion. Analysis of the genetic data indicates that French and Korean populations likely arose from two independent introduction events. The most probable source population is from an area between the Chinese provinces of Zhejiang and Jiangsu. This invasion route is in agreement with knowledge on trade and historical records. By studying colonies of V. velutina, we demonstrated its polyandry, which is very rare among Vespidae. This mating behavior could have favored the success of this Asian hornet in Europe and Korea. Combined, the population and colony results suggest that very few or possibly only one single multi-mated female gave rise to the invasion