The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

BACKGROUND: The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP). However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. RESULTS: The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. CONCLUSION: Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is coincidental with the decline of earliest settlers' population during this period

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

Abstract Background The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP). However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. Results The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. Conclusion Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is coincidental with the decline of earliest settlers' population during this period.</p

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage-2

Ur additional complete mtDNA sequence of M2 lineage (labeled as R102, T3, T11 and T27) are acquired from published sources [] has been used for tree reconstruction. Suffixes A, C, G, and T indicate transversions, "d" signifies a deletion and a plus sign (+) an insertion; recurrent mutations are underlined. The prefix "@" indicates back mutation. The coalescent estimates were calculated as per [] and [] presented as bold and Italic respectively.<p><b>Copyright information:</b></p><p>Taken from "The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage"</p><p>http://www.biomedcentral.com/1471-2148/8/230</p><p>BMC Evolutionary Biology 2008;8():230-230.</p><p>Published online 11 Aug 2008</p><p>PMCID:PMC2528015.</p><p></p

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage-0

Ur additional complete mtDNA sequence of M2 lineage (labeled as R102, T3, T11 and T27) are acquired from published sources [] has been used for tree reconstruction. Suffixes A, C, G, and T indicate transversions, "d" signifies a deletion and a plus sign (+) an insertion; recurrent mutations are underlined. The prefix "@" indicates back mutation. The coalescent estimates were calculated as per [] and [] presented as bold and Italic respectively.<p><b>Copyright information:</b></p><p>Taken from "The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage"</p><p>http://www.biomedcentral.com/1471-2148/8/230</p><p>BMC Evolutionary Biology 2008;8():230-230.</p><p>Published online 11 Aug 2008</p><p>PMCID:PMC2528015.</p><p></p

The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage-1

PD) limits. Panel 'A'- The Bayesian skyline plot (= 10) for India total, derived from complete mtDNA sequences (= 76). Panel 'B'- The Bayesian skyline plot (= 10) for India total, derived from coding region (577–16023) mtDNA sequences (= 76). The time estimates (yBP) were calculated as per []. For comparison, the cold and arid period around the Last Glacial Maximum are also indicated on panel A & B. Panel 'C to F' shows Bayesian skyline plots (= 10) derived from complete mtDNA sequences of eastern (n = 11), central (n = 29), southern (n = 14) and western (n = 22) regions of India respectively.<p><b>Copyright information:</b></p><p>Taken from "The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage"</p><p>http://www.biomedcentral.com/1471-2148/8/230</p><p>BMC Evolutionary Biology 2008;8():230-230.</p><p>Published online 11 Aug 2008</p><p>PMCID:PMC2528015.</p><p></p

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate&ndash;severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate&ndash;severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration