SCUBE3 loss-of-function causes a recognizable recessive developmental disorder due to defective bone morphogenetic protein signaling

Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) is a member of a small family of multifunctional cell surface-anchored glycoproteins functioning as co-receptors for a variety of growth factors. Here we report that bi-allelic inactivating variants in SCUBE3 have pleiotropic consequences on development and cause a previously unrecognized syndromic disorder. Eighteen affected individuals from nine unrelated families showed a consistent phenotype characterized by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. In vitro functional validation studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, and their dysregulating effect on bone morphogenetic protein (BMP) signaling. We show that SCUBE3 acts as a BMP2/BMP4 co-receptor, recruits the BMP receptor complexes into raft microdomains, and positively modulates signaling possibly by augmenting the specific interactions between BMPs and BMP type I receptors. Scube3(-/-) mice showed craniofacial and dental defects, reduced body size, and defective endochondral bone growth due to impaired BMP-mediated chondrogenesis and osteogenesis, recapitulating the human disorder. Our findings identify a human disease caused by defective function of a member of the SCUBE family, and link SCUBE3 to processes controlling growth, morphogenesis, and bone and teeth development through modulation of BMP signaling.Genetics of disease, diagnosis and treatmen

Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe

Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process

Unique loss of the PYHIN gene family in bats amongst mammals: Implications for inflammasome sensing

10.1038/srep21722Scientific Reports62172

Petrogenesis and chronology of lunar meteorite Northwest Africa 4472: a KREEPy regolith breccia from the Moon

Northwest Africa (NWA) 4472 is a polymict lunar regolith meteorite. The sample is KREEP-rich (high concentrations of potassium, rare earth elements and phosphorus) and comprises a heterogeneous array of lithic and mineral fragments. These clasts and mineral fragments were sourced from a range of lunar rock types including the lunar High Magnesian Suite, the High Alkali Suite, KREEP basalts, mare basalts and a variety of impact crater environments. The KREEP-rich nature of NWA 4472 indicates that the sample was ejected from regolith on the nearside of the Moon in the Procellarum KREEP Terrane and we have used Lunar Prospector gamma-ray remote sensing data to show that the meteorite is most similar to (and most likely sourced from) regoliths adjacent to the Imbrium impact basin. U–Pb and Pb–Pb age dates of NWA 4472 phosphate phases reveal that the breccia has sampled Pre-Nectarian (4.35 Ga) rocks related to early episodes of KREEP driven magmatism. Some younger phosphate U–Pb and Pb–Pb age dates are likely indicative of impact resetting events at 3.9–4 Ga, consistent with the suggested timing of basin formation on the Moon. Our study also shows that NWA 4472 has sampled impact melts and glass with an alkali-depleted, incompatible trace element-rich (high Sc, low Rb/Th ratios, low K) compositional signature not related to typical Apollo high-K KREEP, or that sampled by KREEPy lunar meteorite Sayh al Uhaymir (SaU) 169. This provides evidence that there are numerous sources of KREEP-rich protoliths on the Moon

Exploring the genome and transcriptome of the cave nectar bat Eonycteris spelaea with PacBio long-read sequencing

10.1093/gigascience/giy116GigaScience71

Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto

10.1038/srep37796Scientific Reports63779