Biology subjects

Auge, G.

Publications and source records attributed to Auge, G..

3 recordsLinked to original sources

bioRxiv2022

Hybrid-derived weedy rice maintains adaptive combinations of alleles associated with seed dormancy

Hybridization is a widespread phenomenon in plants and is a pathway for the evolution of adaptive traits. However, this process may also affect the persistence of combinations of adaptive alleles evolved through natural selection when hybridization occurs between adapted and non-adapted populations. Hybridization between weedy and cultivated rice has been confirmed with an adaptive introgression of deep seed dormancy alleles from cultivated rice. In this study, we explored the influence of hybridization on the conservation of combinations of adaptive alleles by evaluating the natural variation in and the genetic structure of genomic regions associated with seed dormancy. Based on sequence variation in the genomic regions associated with seed dormancy, we revealed that hybrid-derived weedy rice strains maintained most of the adaptive combinations for this trait that were observed in the parental weedy rice, despite equal representation of the parental weedy and cultivated rice in the whole genome sequence. Moreover, the hybrid-derived weedy rice strains had deeper seed dormancy than their parental weedy rice strains. This study suggests that hybridization between weedy rice (having adaptive allelic combinations for seed dormancy) and cultivated rice (having non-adaptive combinations) generates weedy rice strains that express deep seed dormancy caused by genome stabilization through the removal of alleles derived from cultivated rice, in addition to the adaptive introgression of deep seed dormancy alleles derived from cultivated rice. Thus, hybridization between adapted and non-adapted populations seems to be reinforcing the trajectory towards the evolution of adaptive traits.

evolutionary biology↗

bioRxiv2021

SLP2/prohibitins aggregates and instability of the PHB complex are key elements in CHCHD10S59L-related disease

CHCHD10 is an ALS/FTD gene, also involved in a large clinical spectrum, that encodes a protein whose precise function within mitochondria is unclear. Here we show that CHCHD10 interacts with the Stomatin-Like Protein 2 (SLP2) to control the stability of the Prohibitin (PHB) complex in the inner mitochondrial membrane. In affected tissues, SLP2 forms aggregates with prohibitins and the instability of the PHB complex results in activation of OMA1 and accelerated OPA1 proteolysis leading to mitochondrial fragmentation, loss of mitochondrial cristae and apoptosis. Abnormal cristae morphogenesis depends on both the PHB complex destabilization leading to MICOS complex instability, via disruption of OPA1/Mitofilin interaction, and the activation of PINK1-mediated pathways. We also show that the increase of mitophagy found in both heart and hippocampus of Chchd10S59L/+ mito-QC mice is PINK1/Parkin-dependent. Thus, SLP2/PHBs aggregates and destabilization of the PHB complex with PINK1 activation are critical in the sequence of events leading to CHCHD10S59L-related disease.

pathology↗

bioRxiv2020

Structural and Functional Comparison of SARS-CoV-2-Spike Receptor Binding Domain Produced in Pichia pastoris and Mammalian Cells

The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from SARS-CoV-2 Spike protein expressed in P. pastoris and in the well established HEK-293T mammalian cell system. RBD obtained from both yeast and mammalian cells was properly folded, as indicated by UV-absorption, circular dichroism and tryptophan fluorescence. They also had similar stability, as indicated by temperature-induced unfolding (observed Tm were 50 {degrees}C and 52 {degrees}C for RBD produced in P. pastoris and HEK-293T cells, respectively). Moreover, the stability of both variants was similarly reduced when the ionic strength was increased, in agreement with a computational analysis predicting that a set of ionic interactions may stabilize RBD structure. Further characterization by HPLC, size-exclusion chromatography and mass spectrometry revealed a higher heterogeneity of RBD expressed in P. pastoris relative to that produced in HEK-293T cells, which disappeared after enzymatic removal of glycans. The production of RBD in P. pastoris was scaled-up in a bioreactor, with yields above 45 mg/L of 90% pure protein, thus potentially allowing large scale immunizations to produce neutralizing antibodies, as well as the large scale production of serological tests for SARS-CoV-2.

biochemistry↗