Human Immunology through the Lens of Evolutionary Genetics

Quintana-Murci, Lluı́s

doi:10.1016/j.cell.2019.02.033

Cited by 121 publications

(110 citation statements)

References 184 publications

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“…Further, RNA-Seq data has been shown useful in clinical practice for pediatric cancers 55 , and this practice could be extended to other diseases. We hypothesize, in concurrence with 17,56 , that processes of disease-and stress-related genes are overrepresented among the DE genes of African American and European American populations in part because the ancestral selection pressure due to disease and stresses (such as temperature and toxins) was very strong, with very different complements of pathogens and stresses in the regions where these populations lived. To survive, humans living in Europe and those living in Western Africa would have had to evolve the ability to resist the diverse prevalent local pathogens and stresses.…”

Section: Discussionmentioning

confidence: 53%

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Singh¹,

Hernandez²,

Aronow³

et al. 2020

Preprint

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The COVID-19 pandemic has affected African American populations disproportionately with respect to prevalence, morbidity, and mortality. Because gene expression profiles represent combined genetic, socioenvironmental, and physiological effects, and could provide therapeutic biomarkers and environmental mitigation strategies, we undertook a large-scale assessment of differential gene expression between African Americans and European Americans. To do this, we mined RNA-Seq datasets from normal and diseased (tumor) conditions whose metadata could be used to evaluate differential patterns. We observed widespread differential expression of genes implicated in COVID-19 and integral to epithelial boundary function, inflammation, infection, and reactive oxygen stress. Notably, expression of the little-studied F8A2 gene is up to 40-fold greater in African Americans. F8A2, like F8A1, encodes HAP40 protein, which mediates early endosome movement. African American gene expression signatures reveal increased number or activity of esophageal glandular cells and lung ACE2-positive basal keratinocytes. These findings have potential to establish prognostic signatures, refine approaches to minimizing risk of severe infection, and improve precision treatment of COVID-19.

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Section: Discussionmentioning

confidence: 53%

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Singh¹,

Hernandez²,

Aronow³

et al. 2020

Preprint

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“…Indeed, our data suggest that Denisovan introgression in New Guinea may be impacting gene expression levels in the Korowai. More broadly, immune challenges have exerted some of the strongest selective forces on humans throughout our species’ history 11 ; transmissible diseases endemic in Indonesia range from malaria (both P. falciparum and P. vivax ) 8 to infections by multiple helminth species and other understudied tropical diseases 2 . Tuberculosis remains a major health concern in the region, with the World Health Organisation reporting nearly half a million new cases in 2017 55 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago

Natri

Bobowik

Kusuma

et al. 2019

Preprint

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34Indonesia is the world's fourth most populous country, host to striking levels of human diversity, regional 35 patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. 36 However, it has been largely excluded from the human genomics sequencing boom of the last decade. 37 To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide 38 CpG methylation and gene expression measurements in over 100 individuals from three locations that 39 capture the major genomic and geographical axes of diversity across the Indonesian archipelago. 40Investigating between-and within-island differences, we find up to 10% of tested genes are differentially 41 expressed between the islands of Mentawai (Sumatra) and New Guinea. Variation in gene expression is 42 closely associated with DNA methylation, with expression levels of 9.7% of genes strongly correlating 43 with nearby CpG methylation, and many of these genes being differentially expressed between islands. 44Genes identified in our differential expression and methylation analyses are enriched in pathways 45 involved in immunity, highlighting Indonesia tropical role as a source of infectious disease diversity and 46 the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-47 island variation in DNA methylation and gene expression, likely driven by very local environmental 48 differences across sampling sites. Together, these results strongly suggest complex relationships between 49 DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the 50 environment. This has implications for the application of genomic medicine, both in critically 51 understudied Indonesia and globally, and will allow a better understanding of the interacting roles of 52 genomic and environmental factors shaping molecular and complex phenotypes. 53 54 55 56 57 58 59 60 61 Modern human genomics does not equitably represent the full breadth of humanity. While genome 62 sequences for people of European descent now number a million or more, most of the world is deeply 63 understudied 1 . This is particularly true of Indonesia 2 , a country geographically as large as continental 64 Europe and the world's fourth largest by population. Genomic diversity in Indonesia is strikingly 65 different to other well-characterized East Asian populations, such as Han Chinese and Japanese, but this 66 diversity is not captured in large global datasets like the 1000 Genomes Project 3 or the Simons Genome 67 Diversity Project 4 . The first Indonesian genome sequences were only reported in 2016 5 with the first 68 representative survey of diversity across the archipelago only appearing in 2019 6 . This extreme lack of 69 representation extends to molecular phenotypes. To our knowledge, only one genome-wide gene 70 expression study has been published 7 from the region, focused exclusively on host-pathogen interactions 71 with P. falciparum. There are...

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“…While understanding these signaling pathways is challenging because of the inherent difficulties of studying intracellular pathogens, the specialized nature of the P. falciparum life cycle presents a unique opportunity to explore this issue. A number of reports that suggest coevolution between microbes and hosts can be found in literature (Chapman and Hill, 2012;Mozzi et al, 2018;Quintana-Murci, 2019). The importance of polymicrobial interactions in this occurrence has also been presented (Rioux et al, 2007).…”

Section: Testing For the Role Of Evsmentioning

confidence: 99%

Extracellular Vesicles Could Carry an Evolutionary Footprint in Interkingdom Communication

Corrêa

Caballero

León

et al. 2020

Front. Cell. Infect. Microbiol.

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Extracellular vesicles (EVs) are minute particles secreted by the cells of living organisms. Although the functional role of EVs is not yet clear, recent work has highlighted their role in intercellular communication. Here, we expand on this view by suggesting that EVs can also mediate communication among interacting organisms such as hosts, pathogens and vectors. This inter-kingdom communication via EVs is likely to have important evolutionary consequences ranging from adaptation of parasites to specialized niches in the host, to host resistance and evolution and maintenance of parasite virulence and transmissibility. A potential system to explore these consequences is the interaction among the human host, the mosquito vector and Plasmodium parasite involved in the malaria disease. Indeed, recent studies have found that EVs derived from Plasmodium infected red blood cells in humans are likely mediating the parasite's transition from the asexual to sexual stage, which might facilitate transmission to the mosquito vector. However, more work is needed to establish the adaptive consequences of this EV signaling among different taxa. We suggest that an integrative molecular approach, including a comparative phylogenetic analysis of the molecules (e.g., proteins and nucleic acids) derived from the EVs of interacting organisms (and their closely-related species) in the malaria system will prove useful for understanding interkingdom communication. Such analyses will also shed light on the evolution and persistence of host, parasite and vector interactions, with implications for the control of vector borne infectious diseases.

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Human Immunology through the Lens of Evolutionary Genetics

Cited by 121 publications

References 184 publications

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

African Americans and European Americans exhibit distinct gene expression patterns across tissues and tumors that are associated with immunologic and infectious functions and environmental exposures

Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago

Extracellular Vesicles Could Carry an Evolutionary Footprint in Interkingdom Communication

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