Unraveling the population history of the Xiongnu to explain molecular and archaeological models of prehistoric Mongolia

This dissertation explores the prehistory of Mongolia during a time when nomadic tribes created the world\u27s first steppe empire in Inner Asia. These aggregated tribes, known to Chinese historians as Xiongnu, ruled from the 3rd century BCE to the 2nd century CE. They came to define steppe polity construction later used by the Mongol Empire under the reign of Chinggis Khan. These nomads moved extensively over the eastern steppe and interacted, both in trade and intermarriage, with peoples from southern Siberia to Xinjiang. However, the Xiongnu as a people are relatively unknown to scholars since they did not possess a written language of their own. Although analysis on ancient skeletal remains of the Xiongnu have opened new avenues of research into their origins, scholars still do not have a comprehensive understanding of these ancient nomads. This study makes an attempt to elucidate questions of the Xiongnu\u27s history and biological structure by examining craniofacial diversity using a methodology known as geometric morphometrics. Using a suite of multivariate statistical analyses to explain group relationships within and among the Xiongnu to groups in the region, this study explains the origins of the Xiongnu in a biological context and makes inferences about genetic exchanges. A quantitative genetic model is used to test group relationships and infer levels of gene flow between groups. Results indicate the Xiongnu were composed of at least two biologically distinct groups. One sample from an elite cemetery in northern Mongolia shares their ancestry with a Bronze Age population from Mongolia, and possibly, to a later migration of Turks, who came to dominate the eastern steppe between the 6th and 8th centuries CE. The Xiongnu also evidence biological similarity with nomads who composed the Mongol Empire, modern-day Mongolians, and some Siberian groups. These results are similar to genetic studies suggesting a mix of Eastern and Western Eurasian haplogroups while also achieving consensus with models of steppe polity formation proposed by archaeologists, who suggest local ties to extra-local groups through interactive exchange networks. Overall, the Xiongnu nomads are very much a part of Mongolia\u27s past with links to its modern peoples

Evolution in an oncogenic bacterial species with extreme genome plasticity: Helicobacter pylori East Asian genomes

<p>Abstract</p> <p>Background</p> <p>The genome of <it>Helicobacter pylori</it>, an oncogenic bacterium in the human stomach, rapidly evolves and shows wide geographical divergence. The high incidence of stomach cancer in East Asia might be related to bacterial genotype. We used newly developed comparative methods to follow the evolution of East Asian <it>H. pylori </it>genomes using 20 complete genome sequences from Japanese, Korean, Amerind, European, and West African strains.</p> <p>Results</p> <p>A phylogenetic tree of concatenated well-defined core genes supported divergence of the East Asian lineage (hspEAsia; Japanese and Korean) from the European lineage ancestor, and then from the Amerind lineage ancestor. Phylogenetic profiling revealed a large difference in the repertoire of outer membrane proteins (including <it>oipA</it>, <it>hopMN</it>, <it>babABC</it>, <it>sabAB </it>and <it>vacA-2</it>) through gene loss, gain, and mutation. All known functions associated with molybdenum, a rare element essential to nearly all organisms that catalyzes two-electron-transfer oxidation-reduction reactions, appeared to be inactivated. Two pathways linking acetyl~CoA and acetate appeared intact in some Japanese strains. Phylogenetic analysis revealed greater divergence between the East Asian (hspEAsia) and the European (hpEurope) genomes in proteins in host interaction, specifically virulence factors (<it>tipα</it>), outer membrane proteins, and lipopolysaccharide synthesis (human Lewis antigen mimicry) enzymes. Divergence was also seen in proteins in electron transfer and translation fidelity (<it>miaA, tilS</it>), a DNA recombinase/exonuclease that recognizes genome identity (<it>addA</it>), and DNA/RNA hybrid nucleases (<it>rnhAB</it>). Positively selected amino acid changes between hspEAsia and hpEurope were mapped to products of <it>cagA</it>, <it>vacA</it>, <it>homC </it>(outer membrane protein), <it>sotB </it>(sugar transport), and a translation fidelity factor (<it>miaA</it>). Large divergence was seen in genes related to antibiotics: <it>frxA </it>(metronidazole resistance), <it>def </it>(peptide deformylase, drug target), and <it>ftsA </it>(actin-like, drug target).</p> <p>Conclusions</p> <p>These results demonstrate dramatic genome evolution within a species, especially in likely host interaction genes. The East Asian strains appear to differ greatly from the European strains in electron transfer and redox reactions. These findings also suggest a model of adaptive evolution through proteome diversification and selection through modulation of translational fidelity. The results define <it>H. pylori </it>East Asian lineages and provide essential information for understanding their pathogenesis and designing drugs and therapies that target them.</p

Evaluation of risk based microbiological criteria for Campylobacter in broiler carcasses in Belgium using TRiMiCri

Campylobacteriosis is the most frequently reported foodborne zoonosis worldwide. Consumer´s exposure to Campylobacter might be reduced by establishing a microbiological criterion (MC) for Campylobacter on broiler meat. In the present study two possible approaches were evaluated, using the freely available software tool for risk based microbiological criteria TRiMiCri (http://tools.food.dtu.dk/trimicri). The first approach was the traditional one that implies a microbiological limit (ML-MC) and the second one which is based on the relative risk estimate (RRL-MC). The analyses were based on Campylobacter quantitative data collected from 28 Campylobacter positive bathes processed in 6 Belgian broiler slaughterhouses. To evaluate the performance of ML-MC, n=6, different c (0,1,2) and m (100,1 000,10 000) were used. Results showed that more than 90% of Campylobacter positive batches were not complying with strict ML criteria based on the m=100 for all applied combination of c. The RRL approach requires a baseline risk which was estimated based on the Campylobacter baseline data collected in Belgium in 2008. Approximately 60% of evaluated Campylobacter positive batches account for higher risk than the baseline risk. For both approaches, application of less stringent criteria results in lower percentage of NC and higher minimum relative residual risks (MRRR; it refers to the change in risk when all batches are sampled and all NC batches undergo treatment that effectively eliminates Campylobacter so they are replaced by zero risk batches). It was also observed that the number of samples (n) had little effect on risk estimates. Additionally, the results from ML-MC and RRL-MC follow the same curve when plotting percentage of NC against MRRR. However, for RRL-MC the percentage of NC batches and MRRR was lower and higher, respectively. To conclude, obtained results indicate that TRiMiCri is a useful and user friendly tool to make a risk based decision on the choice of the MC

Doctor of Philosophy

dissertationThis study set out to sequence the hypervariable segment-I (HVS-I) of the mitochondrial genome from prehistoric skeletal remains associated with Aleut, Sadlermiut, Dorset and Thule groups in Northern North America in an effort to gain insight into their genetic prehistories. Sequences obtained from said ancient populations (Aleut n=6; Sadlermiut n=7; Thule (partial sequences) n=3) were compared to each other as well as those from contemporary and prehistoric populations in the surrounding area. The prehistoric populations under investigation harbored matrilineages typically found in circum-Arctic populations throughout time: A2, A2a, A2b1, D2/D2a’b/D2a/D2a1 and D4b1a2a1. Ancient Aleuts exhibited HVS-I polymorphisms associated with haplogroups A2a, D2 and D2a’b, while the Sadlermiut were characterized as A2b1 and D4b1a2a1. Partial Thule HVS-I sequences indicate A2 but preclude definitive assignment to A2, A2a or A2b1 until the remaining portion of HVS-I is sequenced. The results indicate ancient Aleuts across time exhibit affinities with the Unangax̂ (modern Aleuts); however, population movement or genetic exchange with neighbors to the east cannot be ruled out at this time. Ancient Aleuts were also found to have a greater matrilineal genetic similarity to Chukotkan populations (Chukchi and Siberian Yuit), rather than those from Kamchatka (Koryak and Itel’men). This genetic similarity/dissimilarity provides additional corroboration for colonization of the Aleutian archipelago being initiated from the east rather than the west. The isolated eastern Arctic Sadlermiut population, on the other hand, was shown to have affinities with contemporary Eskimo (Inuit and Iñupiat). The implications of this points towards the Sadlermiut having Neo-Eskimo rather than Paleo-Eskimo ancestry and echoes previous findings of matrilineal discontinuity in the eastern Arctic. The mtDNA (mitochondrial deoxyribonucleic acid) profiles of the ancient populations in this study are also congruent with results from other mtDNA studies indicating the genetic prehistory of the Neo-Eskimo was distinct from that of the Paleo-Eskimo and inhabitants of the Aleutians. Overall the findings in this study speak to matrilineal genetic relationships of prehistoric and contemporary populations in the most northern stretches of the New World while touching upon population movements in the region

The zoonotic pathogen Helicobacter heilmannii from feline origin : aspects of virulence and gastric colonization

Gastrale Helicobacter species, afkomstig van dieren, kunnen net zoals de typisch humane bacterie Helicobacter pylori de maag van de mens koloniseren en ziekte veroorzaken. Deze zogenaamde niet-H. pylori Helicobacter species (NHPH) werden reeds geassocieerd met gastritis, maagulcera en mucosa-geassocieerde-lymfoïd-weefsel (MALT) lymfomen. Bovendien is het risico op het ontwikkelen van MALT lymfomen hoger na een infectie met gastrale NHPH dan met H. pylori. NHPH omvatten een groep van nauwverwante maar verschillende Helicobacter species die worden teruggevonden in verschillende diersoorten. Zo koloniseren H. felis, H. salomonis, H. bizzozeronii, H. heilmannii, H. cynogastricus en H. baculiformis de maag van hond en kat, terwijl H. suis voornamelijk wordt teruggevonden in varkens. Gastrale NHPH zijn bijzonder moeilijk te kweken in het laboratorium, waardoor er wereldwijd maar weinig in vitro isolaten beschikbaar zijn. H. heilmannii werd in 2011 voor het eerst succesvol geïsoleerd uit kattenmagen en in vitro in cultuur gebracht. Dit doctoraatsonderzoek had tot doel om een beter inzicht te verwerven in de pathogenese van maaginfecties met H. heilmannii, om de mogelijke virulentiefactoren van H. heilmannii in kaart te brengen en om het repertoire aan buitenste membraan-proteïnen van deze kiem te vergelijken met deze van andere gastrale Helicobacter species

The evolutionary role of human-specific genomic events

In the short evolutionary time since the human-chimpanzee divergence, approximately 6.6 million years ago, humans have acquired a range of traits that are unique among primates. These include tripling brain size, enhanced cognitive abilities, complex culture, descended larynx structure that enables spoken language, longevity, specific diseases, inferior olfaction, and (in some human populations) adult lactase persistence. These traits were likely to have evolved through various genomic mechanisms, among them gene duplications and gene-culture co-evolution. Several studies have estimated the dates for some of these human lineage genomic events. However, no study to date has performed a genomewide estimate of the dates of all human gene duplications. Moreover, as many of these traits were likely to have evolved via gene-culture coevolutionary mechanisms, investigating the evolution of one of these human-specific traits – lactase persistence – provides a model example for in-depth future investigations of specific human phenotypes. In this study I have investigated an important class of human-specific genomic events – gene duplications (otherwise known as human inparalogues). I have developed a new bioinformatics approach for detecting human lineage-specific inparalogues and the duplication dates for those genes. I show that human-specific inparalogues are non-randomly distributed among biological function classes, and their duplication event dates are non-randomly distributed on a timeline between the date of the human-chimpanzee split and the present. I have also investigated the evolution of the human-specific polymorphic trait – lactase persistence. I have performed a worldwide correlation analysis comparing frequency data on all currently known lactase persistence-associated alleles and the distribution of the lactase persistence phenotype in different human populations. I have also performed a gene-culture co-evolution analysis, employing spatially explicit simulation and Approximate Bayesian Computation to condition simulations on genetic and archaeological data, in order to make inferences on the evolution of lactase persistence and dairying in Europe