Complete Mitochondrial Genomes Reveal Neolithic Expansion into Europe

The Neolithic transition from hunting and gathering to farming and cattle breeding marks one of the most drastic cultural changes in European prehistory. Short stretches of ancient mitochondrial DNA (mtDNA) from skeletons of pre-Neolithic hunter-gatherers as well as early Neolithic farmers support the demic diffusion model where a migration of early farmers from the Near East and a replacement of pre-Neolithic hunter-gatherers are largely responsible for cultural innovation and changes in subsistence strategies during the Neolithic revolution in Europe. In order to test if a signal of population expansion is still present in modern European mitochondrial DNA, we analyzed a comprehensive dataset of 1,151 complete mtDNAs from present-day Europeans. Relying upon ancient DNA data from previous investigations, we identified mtDNA haplogroups that are typical for early farmers and hunter-gatherers, namely H and U respectively. Bayesian skyline coalescence estimates were then used on subsets of complete mtDNAs from modern populations to look for signals of past population expansions. Our analyses revealed a population expansion between 15,000 and 10,000 years before present (YBP) in mtDNAs typical for hunters and gatherers, with a decline between 10,000 and 5,000 YBP. These corresponded to an analogous population increase approximately 9,000 YBP for mtDNAs typical of early farmers. The observed changes over time suggest that the spread of agriculture in Europe involved the expansion of farming populations into Europe followed by the eventual assimilation of resident hunter-gatherers. Our data show that contemporary mtDNA datasets can be used to study ancient population history if only limited ancient genetic data is available

<i>Clostridium scindens</i> colonization of gnotobiotic mice promotes a chronic unresolving infection with <i>Clostridioides difficile</i>

AbstractThe commensal Clostridium scindens has been regarded as a promising bacteriotherapeutic against Clostridioides difficile infection due to its ability to consume host factors that can promote C. difficile growth, and its production of the antimicrobial compound 1-acetyl-β-carboline. We investigated C. scindens’ protective effects against C. difficile using defined colonization studies in gnotobiotic mice. Mice infected with C. difficile develop lethal infection within 48 hours. In contrast, 88% of mice pre-colonized with C. scindens survived acute infection with delayed C. difficile colonization, lower biomass, and toxin B levels at 24 hours after infection. However, two weeks post-challenge, surviving mice showed comparable levels of cecal C. difficile vegetative and spore biomass and toxin B, as seen during acute infection. After two weeks, co-colonized mice exhibited mucosal colonic hyperplasia with focal pseudomembranes, modeling a chronic and recurrent infection state. Our findings illustrate how the commensal microbiota can modulate host and pathogen interactions leading to chonic C. difficile carriage and infection.</jats:p