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Post by Admin on Aug 14, 2022 23:39:19 GMT
It has been suggested that early Y. pestis dispersals across Eurasia followed human migration from the Eurasian steppe.11 Such a hypothesis followed the observation that all LNBA individuals from whom ancient Y. pestis genomes were isolated carried steppe-related ancestry in their genome and that the phylogeny of the LNBA Y. pestis genomes indicated the same directional spread. To investigate this observed correlation, we additionally enriched the HGC009 and HGC068 genomic libraries, as well as those of HGC004 and HGC040, for circa 1.24 million ancestry-informative SNPs on the human nuclear genome (“1240K SNP capture”) of which 583,793 were successfully recovered in HGC009 and 285,259 in HGC040. Lower SNP yields were recovered for HGC068 (5,508 SNPs) and HGC004 (2,968 SNPs), and therefore, these specimens were not included in downstream analyses. Given this low number of SNPs, it cannot be excluded that samples HGC009 and HGC068 were teeth from the same individual, while the unique SNPs of the HGC004 and HGC040 S. enterica genomes indicate that these were two distinct strains, therefore infecting two different individuals. Figure 3 For HGC009 and HGC040, we performed a principal-component analysis (PCA) using modern West Eurasian populations as a scaffold onto which we projected HGC009, HGC040, and other relevant ancient populations. Our results revealed that both HGC009 and HGC040 cluster with other individuals from Hagios Charalambos and Moni Odigitria from Bronze Age Crete.19 They are all shifted from the cluster of Greek Neolithic genomes in the direction of Chalcolithic-Bronze Age Anatolia (Figure 3A). With qpAdm,33 we showed that similar to the other Bronze Age individuals from Crete,19 HGC009 and HGC040 can be adequately modeled with additional ancestry from eastern sources, notably Chalcolithic Anatolia and the Caucasus (Figure 3B) or Chalcolithic Iran (Iran_C) (p values > 0.05). However, only models with Chalcolithic Anatolia fit when the target is the group of all the other individuals from Hagios Charalambos.19 Models with sources representing the Bronze Age “steppe” ancestry (e.g., Samara-Caucasus Steppe), or LNBA Central Europeans who received gene flow from the former (e.g., C. Europe associated with the Corded Ware phenomenon), consistently failed at all times (p values for fit model to the data <<0.05). In contrast to the evidence from the rest of Europe, this indicates that if the disease reached Bronze Age Crete through contact with mobile peoples from outside Crete and non-related to Anatolia, they were small in number and left no trace in the Early Bronze Age archaeogenetic record of the island. Whereas direct human-to-human contact based on the island’s interconnectedness through mobility and trade is one possible way, the involvement of wild and/or domestic animals as hosts also needs to be considered, as plague is a zoonotic disease.
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Post by Admin on Aug 16, 2022 0:49:47 GMT
The genetic data suggest that the individuals investigated here were most probably inhabitants of Crete, living at the end of the 3rd millennium BCE (2290–1909 calBCE). This period is of special interest because it witnessed a series of major transformations across the Eastern Mediterranean, most notably the collapse of the Egyptian Old Kingdom and the Near Eastern Akkadian State.1,2 The reasons for these developments have long been under debate, whereby climatic factors and especially severe droughts were emphasized as consequences of the so-called 4.2 ka BP climatic event.2 In the Aegean, the late 3rd millennium (Early Helladic III) witnessed the decline of the complex interconnected societies that had emerged around 2700 BCE on the Greek mainland (Early Helladic II).3,34 This drastic change was commonly explained by various reasons, such as environmental factors (e.g., erosion due to excessive land use), or climate and the migration or even invasion of people,4,34,35 but only rarely were infectious diseases taken into consideration.36 Additionally, the proposed events are not clearly visible across all potentially affected regions. On Crete, there is no apparent crisis at the end of the Early Minoan II period, and the transition between Early Minoan III and Middle Minoan IA periods (ca. 2300–2000/1900 BCE) is not clearly understood. These periods are nevertheless of particular importance because they directly preceded the emergence of the well-known Old Palaces during Middle Minoan IB at the very latest. Although some scholars have described continuity for this period,37,38 others have argued for a phase of societal and population decline in large parts of Crete during Early Minoan III. They report the abandonment of a number of settlements and the subsequent formation of new ones, shortly before the building of the first palaces started in Middle Minoan IB around 1900 BCE.39,40
Both pathogens, Y. pestis and S. enterica subsp. enterica, which were identified in this study at the site of Hagios Charalambos from this time of transition, can cause severe epidemics in human populations. Y. pestis was responsible for at least three major pandemics in human history: the Justinianic plague, or first pandemic (540/41–750 CE), the Black Death/second pandemic (ca. 1346 until the 18th century CE), and the third pandemic (1855 until mid-20th century CE).5 Archaeogenetic studies have shown that this pathogen was already present in a wide geographic range between central Europe and Siberia from the Middle Neolithic onward and especially during the Bronze Age.9, 10, 11, 12, 13 However, genetic evidence for the presence of Y. pestis in the Eastern Mediterranean during this period has been lacking so far. The S. enterica genomes from Hagios Charalambos are part of the so-called Para C lineage, which comprises the three serovars Paratyphi C, Typhisuis, and Cholerasuis. At present, S. enterica Paratyphi C, together with Typhi, Paratyphi A and B, account for ca. 6 million cases of enteric fever in humans annually, with an estimated 54,000 deaths worldwide.41 Ancient genomes from the Paratyphi C serovar were recently isolated from individuals of two medieval mass burials in the north German city of Lübeck, dating to the second half of the 14th century, suggesting an outbreak of paratyphoid fever.42 It was also identified at a 16th century mass burial site in Mexico city, which is associated with the devastating “cocoliztli” epidemic.43
The ancient pathogen genomes presented here belong to lineages of Y. pestis and S. enterica that lack any modern representatives. In addition, the Y. pestis genome is possibly not yet adapted to effective transmission via the flea vector and thus might have caused a different form of plague than the bubonic one, which is caused after the bacterium enters the lymphatic system from the location of the flea bite.Possible routes are the less efficient early phase transmission, which does not require blockage of the flea gut through biofilm formation,44, 45, 46, 47 airborne transmission (as in the pneumonic form of plague, which has been previously proposed),48 or similarly to its closest relative, Yersinia pseudotuberculosis, via the fecal-oral route. As such, modern Y. pestis strains have the potential to also infect a variety of domesticated animals49, 50, 51 and can be transmitted to humans through the consumption of contaminated meat49,52, 53, 54 or the handling of the infected animals.55 As for S. enterica, the serovars Paratyphi C, Typhisuis, and Cholerasuis, which account for the majority of strains in the Para C lineage, are restricted to humans and/or pigs as their hosts. Consistent with the fact that pseudogenization has been linked to host adaptation,26,56,57 these strains show a higher number of pseudogenes than other non-host restricted S. enterica serovars.25 However, the frequency of pseudogenes in ancient strains from this lineage, such as ETR001 and XBQM20/XBQM90, as well as SUA004, with which HGC004 and HGC040 form a distinct branch, is in the range of non-host adapted serovars, suggesting that these strains were rather host generalists.25,58 In addition, these ancient genomes are lacking the Salmonella pathogenicity island SPI-7, which comprises a series of virulence genes including the Vi capsular polysaccharide operon.59,60 It is associated with evasion of the immune system and typhoid fever and is present in only a few serovars, such as the human restricted serovars Typhi and Paratyphi C.
Therefore, the virulence and mode of transmission of these two pathogen strains from Hagios Charalambos remains uncertain, as does their potential to cause epidemic events. Moreover, their impact on the population and societies of Crete, especially during the transition from the Early Minoan III to Middle Minoan I, is difficult to infer from a restricted dataset derived from a single archaeological site, specifically in the case of Hagios Charalambos where all human remains were recovered from secondary burials. Future screening of more individuals from this region and period for the presence of pathogens will be essential for providing a more detailed picture of infectious disease impact in this region during the end of the 3rd millenium BCE.
Nevertheless, the occurrence of these two pathogens on the island of Crete is of significance. Both Y. pestis and S. enterica were previously shown to have had a wide distribution in Eurasia during the same period,10,11,13,25,58 and given the existence of well-established trading networks in the Bronze Age Eastern Mediterranean,61, 62, 63 our findings suggest that both pathogens may have also been circulating in neighboring areas from which they were introduced. Further, if both pathogens were present in remote areas such as the Lasithi plateau, they possibly also reached larger settlements in other parts of Crete. There, higher population densities could have facilitated the transmission to a great number of individuals.
While it is unlikely that Y. pestis or S. enterica were the sole culprits responsible for the societal changes observed in the Mediterranean at the end of the 3rd millennium BCE, we propose that, given the aDNA evidence presented here, infectious diseases should be considered as an additional contributing factor; possibly in an interplay with climate and migration, which has been previously suggested.36 Incoming peoples with their livestock could have introduced both diseases to which the local population may have not been previously exposed. Moreover, the massive droughts described in association with the 4.2 ka BP climatic event could have resulted in a shortage of clean drinking water and an immunologically weakened population with higher susceptibility to infectious diseases.36,64 As infections by some pathogens, such as Y. pestis and S. enterica, are not manifested osteologically, these diseases and their impacts have often been unnoticed in the archaeological record in the absence of other evidence (e.g., multiple burials). Therefore, archaeogenetic studies provide an important tool to identify pathogens that affected past populations and, as a result, reveal a more complete picture of their lives and health as well as the pathogens’ evolution.
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