Project description:While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence. 14 human and 6 chimpanzee samples were sequenced.
Project description:While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence.
Project description:For a long time, Neanderthals were considered hunters of large mammals, whereas the diversification of the exploited faunal spectrum to include smaller taxa, including birds, was assumed to be specific to anatomically modern humans. In recent decades, archaeozoological analyses of faunal remains from layers associated with Middle Palaeolithic lithic industries have revealed traces of human manipulation of small taxa, indicating the exploitation of a wider range of animals than previously thought, including small or fast-moving animals such as molluscs, leporids and birds. These new data have challenged the view that Neanderthals did not exploit small animals, thereby narrowing the behavioral gap with anatomically modern humans. Nevertheless, the information currently available comes almost exclusively from southern Europe and the nature of Neanderthal small fauna exploitation in northern Europe remains largely unknown. The present study aims to fill this gap by applying archaeozoological methods, including detailed taphonomic and traceological analyses, to 118 bird remains recovered from levels containing Middle Palaeolithic industries at Scladina cave, southern Belgium. Analyses of proteomics were applied to clarify the taxonomic identity of two morphologically non-diagnostic elements. Compared to mammal remains, bird bones, most of which belong to the order Galliformes, are scarce at Scladina Cave. This is likely due to conservation bias. Traces of non-human predators or scavengers, suggest that mammalian carnivores are responsible for accumulating a considerable portion of the avian assemblage. In total, seven bird bones exhibit anthropogenic traces, and one element presents questionable traces. Various Galliformes and a cormorant were exploited likely for their meat, during MIS 5 and/or 6 and MIS 6. The terminal posterior phalanx (talon) of a raptor of the size of a pomarine eagle displays intense polishing that could be linked to human manipulation of this element (MIS 5 and/or 6), although in the absence of tool marks this remains hypothetical at this stage. On the radius of a Western capercaillie, two deep incisions may indicate bone working, and intense use-wear on one of the fractured ends indicates that the bone has been utilized, potentially on soft organic material (MIS 6). This study provides the first evidence of the exploitation of birds during the Middle Palaeolithic in Belgium and constitutes the only detailed archaeozoological analysis of bird material in northwestern Europe. The likely transformation and use of a bird bone is only the second example recovered from Neanderthal occupations. The novel taxa identified as Neanderthal prey highlight the plasticity of Neanderthal ecological behavior, adapting to different landscapes and climates and exploiting the full spectrum of locally available prey.
Project description:Mitochondria contain a 16kb-dsDNA genome encoding 13 proteins essential for respiration, whereas its regulatory mechanism and potential role in cancer development remain elusive. Although Methyl-CpG-binding protein (MBD) proteins are essential for nuclear transcription, their role in mitochondrial DNA (mtDNA) transcription is unknown. Here, we report that the MBD2c splicing variant translocates into mitochondria to mediate mtDNA transcription and increase mitochondrial respiration in triple negative breast cancer (TNBC) cells. Specifically, MBD2c binds D-loop regions in mtDNA to recruit SIRT3, which in turn deacetylates TFAM, a primary mitochondrial transcription factor, and activates its function. TFAM activation subsequently enhances transcription of the whole mitochondrial genome. Furthermore, MBD2c overexpression recovered the decreased mtDNA-encoded RNA and protein levels induced by the DNA synthesis inhibitor, cisplatin (CDDP), in vitro and in vivo, preserving mitochondrial gene expression and respiration, consequently enhancing TNBC cells drug resistance and proliferation. These data collectively demonstrate that MBD2c positively regulates mtDNA transcription, thus connecting epigenetic regulation by deacetylation with cancer cell metabolism, suggesting druggable targets to overcome resistance.
Project description:We report mitochondrial genome (mtDNA) sequences in purified mouse muscle stem cells at different ages. This study identifies changes in the mitochondrial genome of muscle stem cells during aging.
Project description:Mitochondria contain a 16kb-dsDNA genome encoding 13 proteins essential for respiration, whereas its regulatory mechanism and potential role in cancer development remain elusive. Although Methyl-CpG-binding protein (MBD) proteins are essential for nuclear transcription, their role in mitochondrial DNA (mtDNA) transcription is unknown. Here, we report that the MBD2c splicing variant translocates into mitochondria to mediate mtDNA transcription and increase mitochondrial respiration in triple negative breast cancer (TNBC) cells. Specifically, MBD2c binds D-loop regions in mtDNA to recruit SIRT3, which in turn deacetylates TFAM, a primary mitochondrial transcription factor, and activates its function. TFAM activation subsequently enhances transcription of the whole mitochondrial genome. Furthermore, MBD2c overexpression recovered the decreased mtDNA-encoded RNA and protein levels induced by the DNA synthesis inhibitor, cisplatin (CDDP), in vitro and in vivo, preserving mitochondrial gene expression and respiration, consequently enhancing TNBC cells drug resistance and proliferation. These data collectively demonstrate that MBD2c positively regulates mtDNA transcription, thus connecting epigenetic regulation by deacetylation with cancer cell metabolism, suggesting druggable targets to overcome resistance.