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Post by Admin on Jun 10, 2022 17:33:36 GMT
Dr Emma Pomeroy - New Neanderthal discoveries at Shanidar Cave, Iraqi Kurdistan 295,984 views Nov 23, 2020 **This lecture contains images of human skeletal remains.**
This presentation was given on 19 November 2020 as part of the Garrod Research seminar series of the McDonald Institute for Archaeological Research, University of Cambridge.
Dr Emma Pomeroy is Lecturer in the Evolution of Health, Diet and Disease in the Department of Archaeology, University of Cambridge.
Abstract: Shanidar Cave is an iconic site in Palaeolithic research thanks to the discoveries of the remains of ten Neanderthal men, women and children by Ralph Solecki and his team between 1951 and 1960. Shanidar 1's extensive injuries during his life have been central to discussions of Neanderthal compassion and care, while the famous 'flower burial' (Shanidar 4, whose body was surrounded by pollen clumps), has been a hotly-contested example of Neanderthal funerary behaviour for decades. New excavations at Shanidar Cave, led by Professor Graeme Barker since 2015 in collaboration with the Kurdish Regional Government's Department of Antiquities, set out to enhance our understanding of the lives of the Shanidar Cave Neanderthals and the modern humans who succeeded them using cutting-edge archaeological techniques. The discovery of new Neanderthal remains from Shanidar 5 and another individual, currently known as Shanidar Z, was unexpected but offers an exceptionally rare opportunity to reconsider and test ideas about Neanderthals' morphology and behaviour. In addition, the recent availability of Ralph Solecki's extensive excavation archives through the Smithsonian Institution's National Anthropological Archive is providing greater context to Solecki's original discoveries and new perspectives on the remains he uncovered. In this seminar, I will discuss the new insights into Neanderthal behaviour and biology emerging from the analyses of the new Shanidar Cave finds and Solecki's archive, and their implications for understanding our enigmatic evolutionary relatives.
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Post by Admin on Jul 5, 2022 14:33:22 GMT
The 60,000-year-old artefact rewriting Neanderthal history – BBC REEL 9,380 views Jul 4, 2022 In 1995, archaeologist Ivan Turk discovered a unique perforated bone in the Divje Babe cave in Slovenia. The artefact was found in the middle of a palaeolithic layer of earth, near the remains of a Neanderthal fire place, stone and bone tools.
Extensive experimental research confirmed that the holes in the bone were hand-made and that the bone was likely a neanderthal flute, between 50,000 to 60,000 years old. This makes it the world’s oldest musical instrument and an object that could re-write our assumptions about the fundamental humanity of our Neanderthal cousins.
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Post by Admin on Jul 5, 2022 15:21:53 GMT
About 60,000 years ago, a human had a sexual encounter with a Neanderthal. Now, a genetic scientist has claimed that this single sexual act caused the deaths of up to a million people during the COVID-19 pandemic.
As of June 12, 2022, 12:26 GMT, the coronavirus COVID-19 outbreak had killed 6,331,211 people. Now, an English scientist has published research into the effect of the genetic differences between the lungs of Covid sufferers. His results, published in Nature Genetics , suggested that just one single “romantic liaison” about 60,000 years ago, between a Neanderthal and a human, caused up to a million deaths during the recent pandemic.
A Single Interspecies Relationship Led “Up to a Million” Covid Deaths While you’ve heard the word “ genes” a thousand times, do you know what a gene actually is? According to MedilinePlus, genes are made up of DNA and represent the basic physical and functional unit of heredity. The microcosmic mysteries were greatly taken away from genes when an international research effort called the Human Genome Project determined the sequence of the human genome’s 3.2 billion letters of DNA, revealing humans have between 20,000 and 25,000 different genes encoded with ancestral data.
At the recent Cheltenham Science Festival , Professor James Davies, associate professor of genomics at Oxford University's Radcliffe Department of Medicine, said one of these genes (LZTFL1) “caused a common genetic quirk that makes lungs susceptible to infection.” The researcher concluded that the offending LZTFL1 gene was passed along in “a single interspecies relationship and a single child,” that led to hundreds of thousands, and up to a million, Covid deaths.
Speaking of the sexual liaison, Professor Simon Underdown, a biological anthropologist at Oxford Brookes University, told the Science Festival that Neanderthal groups were widely dispersed and only comprised around 20 to 25 individuals. He agrees that it was a single sexual liaison that led to many modern humans having bad reactions to severe forms of Covid. However, he highlighted how “remarkable” it was that a Neanderthal should meet a Homo sapiens and have a one-off sexual encounter that created the Covid-weakening pulmonary gene in modern humans.
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Post by Admin on Jul 5, 2022 22:14:01 GMT
Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) disease (COVID-19) pandemic has caused millions of deaths worldwide. Genome-wide association studies identified the 3p21.31 region as conferring a twofold increased risk of respiratory failure. Here, using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial–mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1. We conclude that pulmonary epithelial cells undergoing EMT, rather than immune cells, are likely responsible for the 3p21.31-associated risk. Since the 3p21.31 effect is conferred by a gain-of-function, LZTFL1 may represent a therapeutic target.
Main The COVID-19 pandemic is estimated to have caused over 4.6 million deaths so far1,2. The predominant cause of mortality is pneumonia and severe acute respiratory distress syndrome3. However, COVID-19 can cause multiple organ failure through cytokine release, microvascular and macrovascular thrombosis, endothelial damage, acute kidney injury and myocarditis4,5,6. Genome-wide association studies (GWAS) are important for identifying candidate genes and pathways that predispose to complex diseases7; genetically validated drug targets are more likely to lead to approved drugs8. Two large GWAS were carried out to determine whether common variants drive susceptibility to severe COVID-19 (refs. 9,10). Both studies identified a region of chromosome 3p21.31 as having the strongest association, while a third study also identified this locus as conferring susceptibility to infection11. The 3p21.31 risk haplotype, which arises from Neanderthal DNA12 and is currently unexplained with regards to the causal variant(s), causal gene(s) and specific role in COVID-19, confers a twofold increased risk of respiratory failure from COVID-19 (refs. 9,10) and an over twofold increased risk of mortality for individuals under 60 (ref. 13). Additionally, the risk variants at this locus are carried by >60% of individuals with South Asian ancestry (SAS), compared to 15% of European ancestry (EUR) groups, partially explaining the ongoing higher death rate in this population in the UK14,15.
Identifying the causal gene(s) and mechanism(s) behind GWAS hits poses several challenges. First, a causative variant is usually in linkage disequilibrium (LD) with many other variants and these can take different forms (SNPs, insertions, deletions and structural polymorphisms). Second, the genetic signals are completely cell type-agnostic, which makes it challenging to identify appropriate experimental models for further investigation. Third, there are multiple mechanisms by which variants can have an effect. Alteration of the protein-coding sequence or RNA splicing, both of which are relatively straightforward to disentangle, account for fewer than 20% of associations in polygenic disease16. The remaining variants and their target gene(s) can be very difficult to decode. Many are thought to lie within cis-regulatory elements17, such as enhancers, which are short DNA sequences that often control tissue- and developmental stage-specific gene expression. Deciphering the variants that affect enhancers is challenging because many enhancers are only active in specific cell types or at specific times; enhancers are often distant in the linear DNA sequence (often 104–106 base pairs (bp)) from the genes they control and the effects of sequence changes are not straightforward to predict.
We developed a comprehensive platform for decoding the effects of sequence variation identified by GWAS16 (Extended Data Fig. 1a). This combines computational and wet lab approaches to delineate the identity of causative variants, the cell types involved and effector genes. Initially, GWAS-identified haplotypes were screened for potential protein-coding sequence variants. Variants altering splice sites were then assessed using a combination of machine learning18 and RNA sequencing (RNA-seq) analysis. Conventional genomic approaches were then combined with machine learning19 to define whether variants were found within, and affected, cis-regulatory sequences from a panel of disease-relevant cell types; this allows for the identification of the key cell type(s) and the determination of the likely causative variant. Subsequently, chromosome conformation capture (3C) analysis20,21,22 was used to identify the gene promoters, which physically contacted the candidate enhancer sequence in the relevant cell type(s); these data were integrated with gene-expression analyses. Finally, genome editing was used to validate the regulatory effects of prioritized variants.
In this study, we applied this approach to identify rs17713054 as a probable causative variant and LZTFL1 as a candidate effector gene in pulmonary epithelial cells as contributing to the strong COVID-19 association at the 3p21.31 locus, with EMT identified as a relevant infection response pathway.
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Post by Admin on Jul 13, 2022 19:02:51 GMT
Life on the blood-thinning agent warfarin involves the careful calculation of each dose. Too little, and it could be ineffective. Too much, and there is the risk of uncontrollable bleeding. According to a recent study, those of us who share specific genes with one of our closest hominin cousins, the Neanderthal, could find this balancing act a little more challenging. The researchers' discovery that variants in enzymes responsible for breaking down pharmaceuticals such as warfarin, ibuprofen, and cholesterol-lowering statins have such ancient origins could help explain why we don't all react to the same medications in the same way. "This is one case where the admixture with Neanderthals has a direct impact in the clinic. Otherwise therapeutic doses can be toxic for carriers of the Neanderthal gene variant," says the study's lead researcher, evolutionary geneticist Hugo Zeberg with Sweden's Karolinska Institute. Advances in genetic sequencing have revealed the extent to which our direct ancestors – the ones who wandered into every corner of the globe over tens of thousands of years – paused to raise families with previous groups of migrants along the way. The legacy of genes passed down from this intermingling is yet to be fully appreciated, though year by year, researchers uncover hints in how genes that evolved in long-lost populations could contribute to differences in our own biology. In many cases, these variations might be fairly trivial. But when it comes to the way an ancestral form of enzyme or protein channel affects our health, it could be important to know as much as we can about its evolution. CYP2C9 is a gene that encodes the cytochrome P450, a superfamily of enzymes in the liver tasked with breaking down a wide range of medicines we commonly use to treat anything from inflammation to epilepsy. It also happens to come in a variety of subtly different shapes, each the result of one of 20 unique takes on CYP2C9's coding. Of course, some of these variations in structure do a better job at metabolising pharmaceuticals than others, meaning the version of CYP2C9 you inherit could determine how long your dose of medicine sticks around in your body. In fact, one type, called CYP2C9*2, is 70 percent less active than the more common CYP2C9*1 gene variant, meaning carriers of CYP2C9*2 might metabolise some pharmaceuticals more slowly. CYP2C9*2 seems to pop up rather frequently with other variants classed as CYP2C8*3, especially in individuals in the same families. This wouldn't be so odd, if not for the fact they happened to be separated by tens of thousands of bases of DNA. Knowing other examples of commonly-paired gene variants spread far apart on our chromosomes have their roots in Neanderthal genomes, Zeberg and his colleagues compared the sequences taken from 146 families to see just how much they varied from similar stretches of code in genetic databases representing other modern and ancestral populations. They found the stretch of DNA containing the two cytochrome gene variants that encode the P450 cytochrome was close enough to the Neanderthal's version that the two genes were almost certainly passed on in a mixing of our family lines tens of thousands of years ago. The researchers note this finding might not make a big difference in how we treat individuals with medications like warfarin or statins. Specialists already keep a close eye on how we process finicky drugs, using frequent blood tests to ensure dosages are kept within reasonable limits. Tracing the origins of variations in such important enzymes could give us a better appreciation of the environment in which they evolved, though, adding context that helps us understand the diversity of health we see today. This research was published in The Pharmacogenomics Journal.
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