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[QUOTE]Originally posted by DD'eDeN: [QB] In Science this week, researchers have reported they have reconstructed the entire genome of the [b]H. pylori that lived in Ötzi’s gut and the results give us an interesting picture into the peopling of Europe approximately 5,000 years ago.[/b] Most H. pylori lives harmlessly in our stomachs. Sometimes this bug can cause ulcers and stomach cancer. I have in the past shared research on how H. pylori has been used as proxy to understand human migrations. The deepest branches of the bacteria’s family tree are found in Africa and as humans expanded to other continents, they took distinctive strains with them. In studying Ötzi’s gut flora, the researchers have found out something very remarkable! [b] Compared to living Europeans, he has a nearly pure ancestral Asian strain of H. pylori.[/b] --- Crimea/Chimera/XyYamMera=sky/seas --- Genomic Signatures of Selective Pressures and Introgression from Archaic Hominins at Human Innate Immunity Genes Matthieu Deschamps cs 2016 Am.J.hum.Gen.98:521 doi http://dx.doi.org/10.1016/j.ajhg.2015.11.014 Human genes governing innate immunity provide a valuable tool for the study of the selective pressure imposed by micro-organisms on host genomes. A comprehensive genome-wide study of how selective constraints & adaptations have driven the evolution of innate immunity genes is missing. Using full-genome sequence variation from the 1000 Genomes Project, - we show that innate immunity genes have globally evolved under stronger purifying selection than the remainder of protein-coding genes: we identify a gene-set under the strongest selective constraints, mutations in which are likely to predispose individuals to life-threatening disease, as illustrated by STAT1 & TRAF3, - we evaluate the occurrence of local adaptation: we detect 57 high-scoring signals of positive selection at innate immunity genes, variation in which has been associated with susceptibility to common infectious or auto-immune diseases, - we show that most adaptations targeting coding variation have occurred in the last 613 ka (when populations shifted from hunting & gathering to farming), - we show that innate immunity genes present higher Hn introgression than the remainder of the coding genome: among the genes presenting the highest Hn ancestry, we find the TLR6-TLR1-TLR10 cluster, which also contains functional adaptive variation in Europeans. This study identifies highly constrained genes that fulfill essential, non-redundant functions in host survival, and reveals others that are more permissive to change‹containing variation acquired from archaic hominins or adaptive variants in specific populations‹improving our understanding of the relative biological importance of innate immunity pathways in natural conditions. _______ Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors Michael Dannemann cs 2016 Am.J.hum.Gen.98:2233 doi http://dx.doi.org/10.1016/j.ajhg.2015.11.015 ... Although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. Archaic humans (who lived in Europe & W-Asia for >200 ky) were probably well adapted to this environment & its local pathogens. It is conceivable that Hs entering Europe & W-Asia, who admixed with them, obtained a substantial immune advantage from the introgression of archaic alleles. Here we document a cluster of 3 Toll-like receptors (TLR6,-1,-10) in Hs that carries 3 distinct archaic haplotypes, indicating repeated introgression from archaic humans: - 2 of these haplotypes are most similar to the Hn genome, - the 3rd haplotype is most similar to the Hd genome. The Toll-like receptors are key components of innate immunity, and provide an important first line of immune defense against bacteria, fungi & parasites. The unusually high allele frequencies & unexpected levels of population differentiation indicate that there has been local positive selection on multiple haplotypes at this locus. We show - the introgressed alleles have clear functional effects in Hs, - archaic-like alleles underlie differences in the expression of the TLR-genes, and are associated with reduced microbial resistance & increased allergic disease in large cohorts. This provides strong evidence for recurrent adaptive introgression at the TLR6-1-10 locus, resulting in differences in disease phenotypes in Hs. _________ Kambiz Kamran 8.1.16 Anthropology.net blog: [b]2 new papers (Am.J.hum.Gen.) document how we should thank Hn & Hd for our allergies & boosted immune systems. [/b] Both studies highlight the functional importance of 3 inherited of Toll-like receptor genes: TLR1, TLR6, TLR10. <https://en.wikipedia.org/wiki/Toll-like_receptor> These Toll-like receptors respond to antigens from bacteria, fungi & parasites, and elicit an inflammatory response, ultimately activating the adaptive immune system. 1) compared 1500 genes known to play a role in the innate immune system from the 1000 Genomes Project, and contrasted it with the genomes of ancient humans. They looked for patterns in variation & change, looking at the timing of change. Most adaptations in protein-coding genes occurred in the last 6 to 13 ka, as human populations shifted from hunting & gathering to farming. Some underwent very little change, indicating constraints. Others have undergone quick selective sweeps likely as a process of selection. The biggest surprise was that the TLR1-6-10 cluster is among the genes presenting the highest Hn ancestry in both Europeans & Asians. 2) also screened Hs genomes for evidence of extended regions with high similarity to the Hn & Hd genomes. They then examined the prevalence of those regions in people from around the world, which led to the same 3 TLR gene, and these introgressed variants offered a selective advantage. The archaic-like variants are thought to increase activity to pathogens ... which in turn may have given greater protection against infection, but also increased the susceptibility of Hs to allergies. Certainly possible as Hn were living in Eurasia for 200 ky before Hs, and had already well exposed & adapted to the local Eurasian pathogens. And by interbreeding with Hn, Hs gained these advantageous adaptations. [/QB][/QUOTE]
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