Archaic Hominin Introgression in Africa Contributes to Functional Salivary MUC7 Genetic Variation

Xu, Duo; Pavlidis, Pavlos; Taşkent, Recep Özgür; Alachiotis, Nikolaos; Flanagan, Colin; DeGiorgio, Michael; Blekhman, Ran; Rühl, Stefan; Gökçümen, Ömer

doi:10.1093/molbev/msx206

Cited by 61 publications

(54 citation statements)

References 75 publications

(82 reference statements)

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“…The predominant mucins in human saliva are the high-molecular-weight mucin MUC5B and the lower molecular-weight mucin MUC7 [54]. MUC5B is a gel-forming mucin [56, 57] and much larger than the soluble and evolutionary younger mucin MUC7 [58, 59]. Recently, the presence of MUC19, another largemolecular-weight mucin in human saliva has been described [60].…”

Section: Host-derived Innate and Immune-related Compounds In Human Samentioning

confidence: 99%

“…An example for that effect may be the observed variations in the number of densly O-glycosylated PTS repeat domains in salivary agglutinins [103] and mucins [104, 105] which are known to interact with microbes through glycan-mediated binding (sections 3.1 and 3.2 ). For example, variations in subexonic PTS copy number repeats in salivary mucin MUC7 underwent rapid evolution in the primate lineage and among other mammalian species [59], and similar mechanisms involving possible pathogenic pressure may explain the observable variations in MUC7 among geographically distinct human populations [58]. …”

Section: Evolution and Coevolution Of Host Glycans And Microbes In The mentioning

confidence: 99%

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Glycan recognition at the saliva – oral microbiome interface

Cross

Rühl

2018

Cellular Immunology

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The mouth is a first critical interface where most potentially harmful substances or pathogens contact the host environment. Adaptive and innate immune defense mechanisms are established there to inactivate or eliminate pathogenic microbes that traverse the oral environment on the way to their target organs and tissues. Protein and glycoprotein components of saliva play a particularly important role in modulating the oral microbiota and helping with the clearance of pathogens. It has long been acknowledged that glycobiological and glycoimmunological aspects play a pivotal role in oral host-microbe, microbe-host, and microbe-microbe interactions in the mouth. In this review, we aim to delineate how glycan-mediated host defense mechanisms in the oral cavity support human health. We will describe the role of glycans attached to large molecular size salivary glycoproteins which act as a first line of primordial host defense in the human mouth. We will further discuss how glycan recognition contributes to both colonization and clearance of oral microbes.

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Section: Host-derived Innate and Immune-related Compounds In Human Samentioning

confidence: 99%

Section: Evolution and Coevolution Of Host Glycans And Microbes In The mentioning

confidence: 99%

Glycan recognition at the saliva – oral microbiome interface

Cross

Rühl

2018

Cellular Immunology

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“…The increasing availability of ancient and present-day human genomes from Africa will also make it easier to study admixture patterns between modern African populations [71] , or between present-day and archaic human groups in Africa [72][73][74] (Figure 1). As the bulk of human evolution happened in this continent, it will not be surprising to find cases of introgression -and adaptive introgression -between different African human groups, once ancient DNA from Africa becomes more readily available.…”

Section: Other Admixture Events In Human Evolutionmentioning

confidence: 99%

“…For example, there is some evidence to suggest that the lactase persistence allele located in a regulatory region of the LCT gene -one of the best-known examples of positive selection in humans [68,69] -was perhaps introduced into Western Eurasia via eastward migrations by steppe hereder populations [65,70] . However, the evidence for this hypothesis is still scant, and more ancient sequences will be needed to determine with certainty exactly how this occurred, if it occurred at all [68] .The increasing availability of ancient and present-day human genomes from Africa will also make it easier to study admixture patterns between modern African populations [71] , or between present-day and archaic human groups in Africa [72][73][74] (Figure 1). As the bulk of human evolution happened in this continent, it will not be surprising to find cases of introgression -and adaptive introgression -between different African human groups, once ancient DNA from Africa becomes more readily available.…”

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confidence: 99%

Something old, something borrowed: Admixture and adaptation in human evolution

Dannemann

Racimo

2018

Preprint

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Almost a decade ago, the sequencing of ancient DNA from archaic humans -Neanderthals and Denisovans -revealed that modern and archaic humans interbred at least twice during the Pleistocene. The field of human paleogenomics has now turned its attention towards understanding the nature of this genetic legacy in the gene pool of present-day humans. What exactly did modern humans obtain from interbreeding with Neanderthals and Denisovans? Were introgressed genetic material beneficial, neutral or maladaptive? Can differences in phenotypes among present-day human populations be explained by archaic human introgression? These questions are of prime importance for our understanding of recent human evolution, but will require careful computational modeling and extensive functional assays before they can be answered in full. Here, we review the recent literature characterizing introgressed DNA and the likely biological consequences for their modern human carriers. We focus particularly on archaic human haplotypes that were beneficial to modern humans as they expanded across the globe, and on ways to understand how populations harboring these haplotypes evolved over time. Genome-wide patterns of archaic admixtureIn 2010, the first sequenced Neanderthal genome provided evidence for gene flow from Neanderthals into the ancestors of present-day non-Africans, around 50,000-60,000 years ago [1][2][3] . Since then, archaic human genomes have yielded ever more insightful discoveries. A few years later, a high coverage genome sequence from a Neanderthal found in the Altai mountains allowed researchers to pin down the proportion of Neanderthal ancestry in non-Africans to be ~2% [4] . In 2017, a second high coverage genome sequence from a Neanderthal in Croatia showed that this individual was more closely related to the introgressing Neanderthal population than the Altai Neanderthal, allowing researchers to detect even slightly higher levels of Neanderthal DNA [5] . In 2018, low-coverage genomes of five additional Neanderthals living between 39,000 and 47,000 years ago allowed a first glimpse at population structure in Neanderthals and showed indications of population turnover in late Neanderthal history [6] . But admixture between different human groups has not been limited to modern humans and Neanderthals. The genome sequence of a previously unknown group, the Denisovans (a sister group to Neanderthals), also contributed to the genomes of present-day people in Oceania, and, to a lower extent, to mainland East and South Asians [7][8][9][10][11][12] . Further admixture episodes have also been suggested, including gene flow from an unsampled "super-archaic" human group into Denisovans [4] , from eastern Neanderthals into Denisovans [4] and from modern humans into Neanderthals [13] (Figure 1). While the signals of shared ancestry between modern and archaic human groups are quite evident, the exact processes by which introgression occurred remain unclear. For example, higher levels of Neanderthal ancestry have been observed in...

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“…Furthermore, there is growing evidence that archaic introgression occurred also within Africa (Labuda et al, 2000;Hammer et al, 2011;Lachance et al, 2012;Hsieh et al, 2016;Xu et al, 2017;Zanolli et al, 2017), raising the exciting possibility that other unknown archaic groups may have contributed to human genetic diversity. Therefore, recent work suggests that apparently distinct species can exchange the genetic material along their evolutionary history (Mallet et al, 2016).…”

Section: Widespread Interbreeding Between Homininsmentioning

confidence: 99%

Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

Dolgova

Lao

2018

Preprint

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The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered.It is currently known that AMH introgressed with archaic hominins once they left the African continent. Current out of African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.Keywords: archaic introgression, fitness, natural selection, Neanderthal, Denisova, anatomically modern humans. Peer-reviewed version available at Genes 2018, 9, 358; doi:10.3390/genes9070358 2 Widespread interbreeding between homininsThe demographic history of anatomically modern humans (AMH) is complex, and involves a large number of migrations, genetic admixtures and introgressions, population extinctions and genetic adaptations, which overlap both in time and in space (see Figure 1). Due to this complexity, the evolutionary history of humankind is still far from being fully understood (Nielsen et al., 2017). During the last 30 years, the most accepted demographic scenario for explaining recent evolution of AMH has been the Out of Africa model (OOA). According to this model, AMH evolved in Africa around 100-200 thousands years ago (kya) in East Africa and migrated to the rest of the world. Classical "pure" OOA assumes that admixture with other archaic populations such as Neanderthals or Denisovans, present at the time of the rise of AMH, either did not occur or was negligible (Lalueza-Fox & Gilbert, 2011). Figure 1. Family tree of the four groups of early humans living in Eurasia 50,000 years ago and the inferred gene flow between the groups due to interbreeding (based on Prüfer et al., 2014;Mondal et al., 2016;Hsieh et al., 2016; Medina-Gomez et al., 2017). The direction and estimated magnitude of inferred gene flow events are shown. Branch lengths and timing of gene flows are not scaled. The dashed line indicates that it is uncertain whether Denisovan gene flow into modern humans in mainland Asia occurred directly or via Oceania. Light violet color indicates introgression events from unknown archaic populations (Ghost).However, genomic studies of ancient DNA have revealed that AMH interbred with other hominid lineages, such as Neanderthals and Denisovans, present in Eurasia up to ∼30,000-50,000 years ago Quach & Quintana-Murci, 2017;Vattathil & Akey, 2015 New studies based on current genetic diversity are suggesting that the events of archaic introgression in AMH did occur out of Africa with other hidden "ghost" archaic populations (Mondal et al., 2016). Furthermore, there i...

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Archaic Hominin Introgression in Africa Contributes to Functional Salivary MUC7 Genetic Variation

Cited by 61 publications

References 75 publications

Glycan recognition at the saliva – oral microbiome interface

Glycan recognition at the saliva – oral microbiome interface

Something old, something borrowed: Admixture and adaptation in human evolution

Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

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