Ancient DNA sheds light on the funerary practices of late Neolithic collective burial in southern France.

The Aven de la Boucle (Corconne, Gard, southern France) is a karst shaft used as a collective burial between 3600 and 2800 cal BCE. The site encompasses the skeletal remains of approximately 75 individuals comprising a large majority of adult individuals, represented by scattered and commingled remains. To date, few studies have explored the potential of ancient DNA to tackle the documentation of Neolithic collective burials, and the funerary selection rules within such structures remain largely debated. In this study, we combine genomic analysis of 37 individuals with archaeo-anthropological data and Bayesian modelling of radiocarbon dates. Through this multidisciplinary approach, we aim to characterize the identity of the deceased and their relationships, as well as untangle the genetic diversity and funerary dynamics of this community. Genomic results identify 76% of male Neolithic individuals, suggesting a marked sex-biased selection. Available data emphasize the importance of biological relatedness and a male-mediated transmission of social status, as the affiliation to a specific male-lineage appears as a preponderant selection factor. The genomic results argue in favour of 'continuous' deposits between 3600 and 2800 BCE, carried out by the same community, despite cultural changes reflected by the ceramic material.

Mutations in MYT1, encoding the myelin transcription factor 1, are a rare cause of OAVS.

BACKGROUND: Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder involving first and second branchial arches derivatives, mainly characterised by asymmetric ear anomalies, hemifacial microsomia, ocular defects and vertebral malformations. Although numerous chromosomal abnormalities have been associated with OAVS, no causative gene has been identified so far. OBJECTIVES: We aimed to identify the first causative gene for OAVS. METHODS: As sporadic cases are mostly described in Goldenhar syndrome, we have performed whole exome sequencing (WES) on selected affected individuals and their unaffected parents, looking for de novo mutations. Candidate gene was tested through transient knockdown experiment in zebrafish using a morpholino-based approach. A functional test was developed in cell culture in order to assess deleterious consequences of mutations. RESULTS: By WES, we identified a heterozygous nonsense mutation in one patient in the myelin transcription factor 1 (MYT1) gene. Further, we detected one heterozygous missense mutation in another patient among a cohort of 169 patients with OAVS. This gene encodes the MYT1. Functional studies by transient knockdown of myt1a, homologue of MYT1 in zebrafish, led to specific craniofacial cartilage alterations. Treatment with all-trans retinoic acid (RA), a known teratogenic agent causing OAVS, led to an upregulation of cellular endogenous MYT1 expression. Additionally, cellular wild-type MYT1 overexpression induced a downregulation of RA receptor ß (RARB), whereas mutated MYT1 did not. CONCLUSION: We report MYT1 as the first gene implicated in OAVS, within the RA signalling pathway.

Neolithic genomic data from southern France showcase intensified interactions with hunter-gatherer communities.

Archaeological research shows that the dispersal of the Neolithic took a more complex turn when reaching western Europe, painting a contrasted picture of interactions between autochthonous hunter-gatherers (HGs) and incoming farmers. In order to clarify the mode, the intensity, and the regional variability of biological exchanges implied in these processes, we report new palaeogenomic data from Occitanie, a key region in Southern France. Genomic data from 28 individuals originating from six sites spanning from c. 5,500 to c. 2,500 BCE allow us to characterize regional patterns of ancestries throughout the Neolithic period. Results highlight major differences between the Mediterranean and Continental Neolithic expansion routes regarding both migration and interaction processes. High proportions of HG ancestry in both Early and Late Neolithic groups in Southern France support multiple pulses of inter-group gene flow throughout time and space and confirm the need for regional studies to address the complexity of the processes involved.

Ubiquitin-Dependent Degradation of Mitochondrial Proteins Regulates Energy Metabolism.

The ubiquitin proteasome system (UPS) regulates many cellular functions by degrading key proteins. Notably, the role of UPS in regulating mitochondrial metabolic functions is unclear. Here, we show that ubiquitination occurs in different mitochondrial compartments, including the inner mitochondrial membrane, and that turnover of several metabolic proteins is UPS dependent. We specifically detailed mitochondrial ubiquitination and subsequent UPS-dependent degradation of succinate dehydrogenase subunit A (SDHA), which occurred when SDHA was minimally involved in mitochondrial energy metabolism. We demonstrate that SDHA ubiquitination occurs inside the organelle. In addition, we show that the specific inhibition of SDHA degradation by UPS promotes SDHA-dependent oxygen consumption and increases ATP, malate, and citrate levels. These findings suggest that the mitochondrial metabolic machinery is also regulated by the UPS.