Correlating Bayesian date estimates with climatic events and domestication using a bovine case study

The tribe Bovini contains a number of commercially and culturally important species, such as cattle. Understanding their evolutionary time scale is important for distinguishing between post-glacial and domestication-associated population expansions, but estimates of bovine divergence times have been hindered by a lack of reliable calibration points. We present a Bayesian phylogenetic analysis of 481 mitochondrial D-loop sequences, including 228 radiocarbon-dated ancient DNA sequences, using a multi-demographic coalescent model. By employing the radiocarbon dates as internal calibrations, we co-estimate the bovine phylogeny and divergence times in a relaxed-clock framework. The analysis yields evidence for significant population expansions in both taurine and zebu cattle, European aurochs and yak clades. The divergence age estimates support domestication-associated expansion times (less than 12kyr) for the major haplogroups of cattle. We compare the molecular and palaeontological estimates for the Bison-Bos divergence

A landscape of genomic alterations at the root of a near-untreatable tuberculosis epidemic

Abstract Background Atypical Beijing genotype Mycobacterium tuberculosis strains are widespread in South Africa and have acquired resistance to up to 13 drugs on multiple occasions. It is puzzling that these strains have retained fitness and transmissibility despite the potential fitness cost associated with drug resistance mutations. Methods We conducted Illumina sequencing of 211 Beijing genotype M. tuberculosis isolates to facilitate the detection of genomic features that may promote acquisition of drug resistance and restore fitness in highly resistant atypical Beijing forms. Phylogenetic and comparative genomic analysis was done to determine changes that are unique to the resistant strains that also transmit well. Minimum inhibitory concentration (MIC) determination for streptomycin and bedaquiline was done for a limited number of isolates to demonstrate a difference in MIC between isolates with and without certain variants. Results Phylogenetic analysis confirmed that two clades of atypical Beijing strains have independently developed resistance to virtually all the potent drugs included in standard (pre-bedaquiline) drug-resistant TB treatment regimens. We show that undetected drug resistance in a progenitor strain was likely instrumental in this resistance acquisition. In this cohort, ethionamide (ethA A381P) resistance would be missed in first-line drug-susceptible isolates, and streptomycin (gidB L79S) resistance may be missed due to an MIC close to the critical concentration. Subsequent inadequate treatment historically led to amplification of resistance and facilitated spread of the strains. Bedaquiline resistance was found in a small number of isolates, despite lack of exposure to the drug. The highly resistant clades also carry inhA promoter mutations, which arose after ethA and katG mutations. In these isolates, inhA promoter mutations do not alter drug resistance, suggesting a possible alternative role. Conclusion The presence of the ethA mutation in otherwise susceptible isolates from ethionamide-naïve patients demonstrates that known exposure is not an adequate indicator of drug susceptibility. Similarly, it is demonstrated that bedaquiline resistance can occur without exposure to the drug. Inappropriate treatment regimens, due to missed resistance, leads to amplification of resistance, and transmission. We put these results into the context of current WHO treatment regimens, underscoring the risks of treatment without knowledge of the full drug resistance profile

Ancient DNA Suggests Dwarf and ‘Giant’ Emu Are Conspecific

) is unclear. King Island Emu were mainly distinguished by their much smaller size and a reported darker colour compared to modern Emu. oxidase subunit I (COI) region (1,544 bp), as well as a region of the melanocortin 1 receptor gene (57 bp) were sequenced using a multiplex PCR approach. The results show that haplotypes for King Island Emu fall within the diversity of modern Emu.These data show the close relationship of these emu when compared to other congeneric bird species and indicate that the King Island and modern Emu share a recent common ancestor. King Island emu possibly underwent insular dwarfism as a result of phenotypic plasticity. The close relationship between the King Island and the modern Emu suggests it is most appropriate that the former should be considered a subspecies of the latter. Although both taxa show a close genetic relationship they differ drastically in size. This study also suggests that rates of morphological and neutral molecular evolution are decoupled

Ancient nuclear genomes enable repatriation of Indigenous human remains.

After European colonization, the ancestral remains of Indigenous people were often collected for scientific research or display in museum collections. For many decades, Indigenous people, including Native Americans and Aboriginal Australians, have fought for their return. However, many of these remains have no recorded provenance, making their repatriation very difficult or impossible. To determine whether DNA-based methods could resolve this important problem, we sequenced 10 nuclear genomes and 27 mitogenomes from ancient pre-European Aboriginal Australians (up to 1540 years before the present) of known provenance and compared them to 100 high-coverage contemporary Aboriginal Australian genomes, also of known provenance. We report substantial ancient population structure showing strong genetic affinities between ancient and contemporary Aboriginal Australian individuals from the same geographic location. Our findings demonstrate the feasibility of successfully identifying the origins of unprovenanced ancestral remains using genomic methods

TBProfiler for automated calling of the association with drug resistance of variants in Mycobacterium tuberculosis. S2 File

Data associated with the paper, "TBProfiler for automated calling of the association with drug resistance of variants in Mycobacterium tuberculosis"

TBProfiler for automated calling of the association with drug resistance of variants in Mycobacterium tuberculosis. S1 File

Data associated with the paper, "TBProfiler for automated calling of the association with drug resistance of variants in Mycobacterium tuberculosis"

Haplotype network for modern Emu (green) and King Island Emu (red).

<p>Concatenated haplotypes of control and COI regions totalling 2638bp each. The black circle indicates a hypothetical haplotype, the distance between each neighbouring haplotype corresponds to the number of substitutions that separate them. Numbers correspond to positions in the mitochondrial genome as mentioned for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018728#pone-0018728-t001" target="_blank">Table 1</a>, underlined numbers represent substitutions that occurred in the cytochrome <i>c</i> oxidase subunit I gene as supposed to the control region.</p

TBProfiler for automated calling of the association with drug resistance of variants in Mycobacterium tuberculosis.

Following a huge global effort, the first World Health Organization (WHO)-endorsed catalogue of 17,356 variants in the Mycobacterium tuberculosis complex along with their classification as associated with resistance (interim), not associated with resistance (interim) or uncertain significance was made public In June 2021. This marks a critical step towards the application of next generation sequencing (NGS) data for clinical care. Unfortunately, the variant format used makes it difficult to look up variants when NGS data is generated by other bioinformatics pipelines. Furthermore, the large number of variants of uncertain significance in the catalogue hamper its useability in clinical practice. We successfully converted 98.3% of variants from the WHO catalogue format to the standardized HGVS format. We also created TBProfiler version 4.4.0 to automate the calling of all variants located in the tier 1 and 2 candidate resistance genes along with their classification when listed in the WHO catalogue. Using a representative sample of 339 clinical isolates from South Africa containing 691 variants in a tier 1 or 2 gene, TBProfiler classified 105 (15%) variants as conferring resistance, 72 (10%) as not conferring resistance and 514 (74%) as unclassified, with an average of 29 unclassified variants per isolate. Using a second cohort of 56 clinical isolates from a TB outbreak in Spain containing 21 variants in the tier 1 and 2 genes, TBProfiler classified 13 (61.9%) as unclassified, 7 (33.3%) as not conferring resistance, and a single variant (4.8%) classified as conferring resistance. Continued global efforts using standardized methods for genotyping, phenotyping and bioinformatic analyses will be essential to ensure that knowledge on genomic variants translates into improved patient care