Leprosy: Ancient and Modern
In medieval Europe, leprosy was greatly feared: Sufferers had to wear bells and were shunned and kept isolated from society. Although leprosy largely disappeared from Europe in the 16th century, elsewhere in the world almost a quarter of a million cases are still reported annually, despite the availability of effective drugs.
Schuenemann
et al.
(p.
179
, published online 13 June; see the 14 June News story by
Gibbons
, p.
1278
) probed the origins of leprosy bacilli by using a genomic capture-based approach on DNA obtained from skeletal remains from the 10th to 14th centuries. Because the unique mycolic acids of this mycobacterium protect its DNA, for one Danish sample over 100-fold, coverage of the genome was possible. Sequencing suggests a link between the middle-eastern and medieval European strains, which falls in line with social historical expectations that the returning expeditionary forces of antiquity originally spread the pathogen. Subsequently, Europeans took the bacterium westward to the Americas. Overall, ancient and modern strains remain remarkably similar, with no apparent loss of virulence genes, indicating it was most probably improvements in social conditions that led to leprosy's demise in Europe.
BackgroundThe automated reconstruction of genome sequences in ancient genome analysis is a multifaceted process.ResultsHere we introduce EAGER, a time-efficient pipeline, which greatly simplifies the analysis of large-scale genomic data sets. EAGER provides features to preprocess, map, authenticate, and assess the quality of ancient DNA samples. Additionally, EAGER comprises tools to genotype samples to discover, filter, and analyze variants.ConclusionsEAGER encompasses both state-of-the-art tools for each step as well as new complementary tools tailored for ancient DNA data within a single integrated solution in an easily accessible format.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-0918-z) contains supplementary material, which is available to authorized users.
SummaryIn large‐scale production processes, metabolic control is typically achieved by limited supply of essential nutrients such as glucose or ammonia. With increasing bioreactor dimensions, microbial producers such as Escherichia coli are exposed to changing substrate availabilities due to limited mixing. In turn, cells sense and respond to these dynamic conditions leading to frequent activation of their regulatory programmes. Previously, we characterized short‐ and long‐term strategies of cells to adapt to glucose fluctuations. Here, we focused on fluctuating ammonia supply while studying a continuously running two‐compartment bioreactor system comprising a stirred tank reactor (STR) and a plug‐flow reactor (PFR). The alarmone ppGpp rapidly accumulated in PFR, initiating considerable transcriptional responses after 70 s. About 400 genes were repeatedly switched on/off when E. coli returned to the STR. E. coli revealed highly diverging long‐term transcriptional responses in ammonia compared to glucose fluctuations. In contrast, the induction of stringent regulation was a common feature of both short‐term responses. Cellular ATP demands for coping with fluctuating ammonia supply were found to increase maintenance by 15%. The identification of genes contributing to the increased ATP demand together with the elucidation of regulatory mechanisms may help to create robust cells and processes for large‐scale application.
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