Genomic insights into pre- and post-contact human pathogens in the New World

Ancient pathogen genomes recovered from archaeological human remains provide primary evidence for infectious diseases that circulated amongst human populations in the past, as well as valuable insights regarding past pathogen macroecology, hostadaptation, spread and emergence. In this dissertation, I leverage recent molecular and computational advances to detect and characterize the genomes of pathogenic bacteria that affected indigenous human populations in the New World pre- and post- 16th century European contact. In the first paper I investigate strain members of the Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis, in geographically dispersed human populations from inland Colombia and coastal Peru. I reconstructed and analyzed three pre-contact MTBC genomes belonging to the sub-clade Mycobacterium pinnipedii, associated with infection in seals and sea lions today. M. pinnipedii strains are hypothesized to have spread to coastal Peruvians via seal-to-human transmission (Bos et al., 2014). However, this ecological model does not explain the spread of M. pinnipedii to inland Colombian human populations. Different ecological models accounting for its inland spread are discussed. The second paper presents Salmonella enterica ssp. enterica Paratyphi C, a cause of enteric fever, as a strong candidate pathogen for the post-contact 1545-1550 CE “cocoliztli” outbreak at Teposcolula-Yucundaa in Southern Mexico. The pathogenic agent of this outbreak is unknown from archaeological and ethnohistorical evidence. In this study I used a broad-scale computational screening approach, the MEGAN ALignment Tool (MALT), and was able to detect S. enterica DNA against a complex environmental DNA background in ten individuals buried in the epidemic cemetery. This was done without prior knowledge of the target organism, thus demonstrating the efficiency of such an approach in identifying ancient pathogens in archaeologically preserved tissues. Genome-wide analyses of the ten S. Paratyphi C genomes are presented. In a third paper I applied MALT to screen for ancient pathogen DNA in the remains of a sub-adult individual from a deviant burial, dated to the 16th or 17th century, in Moneen Cave, Ireland. Negative results are reported for the presence of ancient pathogen DNA. Instead this paper focuses on the reconstruction and analysis of this individual’s mitochondrial genome

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Revised version. Minor changes made.I denne masteravhandlinga analyserar eg romanane Evig Søndag av Linnéa Myhre og Svart Belte av Marianne Clementine Håheim. I desse verka følgjer lesaren Linnéa og Marianne gjennom sin kamp for å overkomme anorexia nervosa og bulimia nervosa. Ved å analysere og samanlikne desse to verka, vil eg argumentere for at dei viser to ulike måtar å portrettere spiseforstyrringar, men begge viser eit realistisk og overtydande bilete av ein slik psykisk sjukdom. Vidare diskuterer eg også sjangeren til bøkene, då eg i denne avhandlinga les dei som både patografiar og romanar. Dette posisjonerer dei innan den verkelegheitsnære framstillinga av sjukdom i ulike medium, som til dømes bøker og bloggar, som har vist seg som ein aukande og populær trend dei siste åra. I denne avhandlinga har eg funne ei kopling mellom åtferda til hovudkarakterane og evna deira til å «verne om» og nære sin eigen sjukdom. Det er også ein klar samanheng mellom måten hovudkarakterane oppfattar sin eigen kropp og korleis dei forstår sin eigen identitet. Både Linnéa og Marianne blir så opphengd i sjukdommen at dei har problem med å forstå kven dei er utan den. Dette viser også det paradoksale med spiseforstyrringar: ønsket om å halde på «prosjektet» kolliderer med ønsket om å bli frisk. Eg argumenterer for at det spekteret av åtferd og forsvarsmekanismar som kjem med slike sjukdommar, og dette viser seg her gjennom korleis forfattarane brukar språket ulikt. Håheim brukar eit meir livleg og poetisk språk enn det Myhre gjer. Dette ser uansett ikkje ut til å undergrave den deprimerte tilstanden som Linnéa finn seg sjølv i, men understrekar den heller.In this MA thesis I analyze the novels Evig Søndag by Linnéa Myhre and Svart Belte by Marianne Clementine Håheim. In these novels the reader follows Linnéa and Marianne as they struggle to overcome anorexia nervosa and bulimia nervosa. By analysing and comparing the two novels I argue that they present two different ways of portraying eating disorders, which can both be described as realistic and convincing accounts of these two mental illnesses. In addition, I discuss aspects of genre, given that both novels are constructed as combinations of pathography and fiction. Both novels belong to a recent trend in contemporary Norwegian literature in which the focus is centered on self-afflicted/self-experiencd illnesses, presented in a combination of various media of communication, such as novels and blogs. One of my central findings is that there is, in both novels, a connection between the main characters' behaviour and their unwavering intent to both protect and nurture their illnesses. Moreover, there is also a clear connection between the ways the main characters perceive their bodies and how they perceive their own identity. Both Linnéa and Marianne get so caught up in their illnesses that they have trouble understanding who they are without it. This also captures the paradox of eating disorders; the need to press on with their “project” collides with the need to get well. I argue that the spectre of behaviour and coping mechanisms with such disorders, is shown by the authors’ different use of language, as Håheim tends to be more vivid and poetic in her use of words compared to Myhre's style of writing. However, this does not seem to undermine the depressive state that Linnéa finds herself in, but rather highlight it.Mastergradsoppgave i nordisk språk og litteraturNOLISP350MAHF-NORDMAHF-LÆN

Multi-omic detection of Mycobacterium leprae in archaeological human dental calculus

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record.publishedVersio

Genomic blueprint of a relapsing fever pathogen in 15th century Scandinavia

Louse-borne relapsing fever (LBRF) is known to have killed millions of people over the course of European history and remains a major cause of mortality in parts of the world. Its pathogen, Borrelia recurrentis, shares a common vector with global killers such as typhus and plague and is known for its involvement in devastating historical epidemics such as the Irish potato famine. Here, we de- scribe a European and historical genome of B. recurrentis, recov- ered from a 15th century skeleton from Oslo. Our distinct European lineage has a discrete genomic makeup, displaying an ancestral oppA- 1 gene and gene loss in antigenic variation sites. Our results illustrate the potential of ancient DNA research to elucidate dynamics of re- ductive evolution in a specialized human pathogen and to uncover aspects of human health usually invisible to the archaeological record

Community-curated and standardised metadata of published ancient metagenomic samples with AncientMetagenomeDir

Ancient DNA and RNA are valuable data sources for a wide range of disciplines. Within the field of ancient metagenomics, the number of published genetic datasets has risen dramatically in recent years, and tracking this data for reuse is particularly important for large-scale ecological and evolutionary studies of individual taxa and communities of both microbes and eukaryotes. AncientMetagenomeDir (archived at https://doi.org/10.5281/zenodo.3980833) is a collection of annotated metagenomic sample lists derived from published studies that provide basic, standardised metadata and accession numbers to allow rapid data retrieval from online repositories. These tables are community-curated and span multiple sub-disciplines to ensure adequate breadth and consensus in metadata definitions, as well as longevity of the database. Internal guidelines and automated checks facilitate compatibility with established sequence-read archives and term-ontologies, and ensure consistency and interoperability for future meta-analyses. This collection will also assist in standardising metadata reporting for future ancient metagenomic studies

Multi-omic detection of <i>Mycobacterium leprae</i> in archaeological human dental calculus

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record.publishedVersio

The population genomic legacy of the second plague pandemic

SummaryHuman populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.Results and discussion STAR★Method

The population genomic legacy of the second plague pandemic

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.publishedVersio

The population genomic legacy of the second plague pandemic

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th-19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics