Potential of combining morphometry and ancient DNA information to investigate grapevine domestication

The goal of this work was to explore the possibility (1) of carrying out both morphogeometric and archaeological DNA analyses on the same grape pips and (2) of comparing different molecular markers to reveal DNA variation, namely Simple Sequence Repeats (SSRs) and Single Nucleotide Polymorphisms (SNPs). We focused on waterlogged seeds originating from three Roman and one medieval archaeological sites in France. Our first results indicate that taking photographs of pips is not detrimental to the preservation of DNA, provided a specific protocol is respected. Regarding the genetic markers, obtaining reliable information in sufficient quantity proved very difficult using SSRs. SNPs have a much more interesting potential, providing greater success rates and reliability. Here in four archaeological pips we studied 842 SNPs, derived from known polymorphisms in several genes, including one gene related to sex. Phylogenies built using these genetic markers indicate that three pips from the Roman site of Gasquinoy are close to modern wild grapevines and/or the female group, while the only medieval pip from Colletière is hermaphrodite and close to the modern cultivated group. Morphogeometrical results are in agreement with these findings. We conclude that the combined use of SNP markers and morphogeometry is promising for deciphering the intricate history of grapevine domestication

A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma.

International audienceSo far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes; risk factors associated with RCC include smoking, obesity and hypertension. A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers. The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene; it also stimulates the transcription of hypoxia inducible factor (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes. We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (ΨKXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K-occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer