scholarly journals A selective sweep in the Spike gene has driven SARS-CoV-2 human adaptation

Cell ◽  
2021 ◽  
Author(s):  
Lin Kang ◽  
Guijuan He ◽  
Amanda K. Sharp ◽  
Xiaofeng Wang ◽  
Anne M. Brown ◽  
...  
Author(s):  
Lin Kang ◽  
Guijuan He ◽  
Amanda K. Sharp ◽  
Xiaofeng Wang ◽  
Anne M. Brown ◽  
...  

SummaryWhile SARS-CoV-2 likely has animal origins1, the viral genetic changes necessary to adapt this animal-derived ancestral virus to humans are largely unknown, mostly due to low levels of sequence polymorphism and the notorious difficulties in experimental manipulations of coronavirus genomes. We scanned more than 182,000 SARS-CoV-2 genomes for selective sweep signatures and found that a distinct footprint of positive selection is located around a non-synonymous change (A1114G; T372A) within the Receptor-Binding Domain of the Spike protein, which likely played a critical role in overcoming species barriers and accomplishing interspecies transmission from animals to humans. Structural analysis indicated that the substitution of threonine with an alanine in SARS-CoV-2 concomitantly removes a predicted glycosylation site at N370, resulting in more favorable binding predictions to human ACE2, the cellular receptor. Using a novel bacteria-free cloning system for manipulating RNA virus genomes, we experimentally validated that this SARS-CoV-2-unique substitution significantly increases replication in human cells relative to its putative ancestral variant. Notably, this mutation’s impact on virus replication in human cells was much greater than that of the Spike D614G mutant, which has been widely reported to have been selected for during human-to-human transmission2,3.


Author(s):  
Lawrence A. Palinkas ◽  
E. Eric Gunderson ◽  
Ralph G. Burr

2020 ◽  
Author(s):  
Nabil Bouizegarene ◽  
maxwell ramstead ◽  
Axel Constant ◽  
Karl Friston ◽  
Laurence Kirmayer

The ubiquity and importance of narratives in human adaptation has been recognized by many scholars. Research has identified several functions of narratives that are conducive to individuals’ well-being and adaptation as well as to coordinated social practices and enculturation. In this paper, we characterize the social and cognitive functions of narratives in terms of the framework of active inference. Active inference depicts the fundamental tendency of living organisms to adapt by creating, updating, and maintaining inferences about their environment. We review the literature on the functions of narratives in identity, event segmentation, episodic memory, future projection, storytelling practices, and enculturation. We then re-cast these functions of narratives in terms of active inference, outlining a parsimonious model that can guide future developments in narrative theory, research, and clinical applications.


2021 ◽  
Vol 21 (3) ◽  
Author(s):  
Adelle Thomas ◽  
Emily Theokritoff ◽  
Alexandra Lesnikowski ◽  
Diana Reckien ◽  
Kripa Jagannathan ◽  
...  

AbstractConstraints and limits to adaptation are critical to understanding the extent to which human and natural systems can successfully adapt to climate change. We conduct a systematic review of 1,682 academic studies on human adaptation responses to identify patterns in constraints and limits to adaptation for different regions, sectors, hazards, adaptation response types, and actors. Using definitions of constraints and limits provided by the Intergovernmental Panel on Climate Change (IPCC), we find that most literature identifies constraints to adaptation but that there is limited literature focused on limits to adaptation. Central and South America and Small Islands generally report greater constraints and both hard and soft limits to adaptation. Technological, infrastructural, and ecosystem-based adaptation suggest more evidence of constraints and hard limits than other types of responses. Individuals and households face economic and socio-cultural constraints which also inhibit behavioral adaptation responses and may lead to limits. Finance, governance, institutional, and policy constraints are most prevalent globally. These findings provide early signposts for boundaries of human adaptation and are of high relevance for guiding proactive adaptation financing and governance from local to global scales.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mary Elizabeth Mathyer ◽  
Erin A. Brettmann ◽  
Alina D. Schmidt ◽  
Zane A. Goodwin ◽  
Inez Y. Oh ◽  
...  

AbstractThe genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.


Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 136
Author(s):  
Bandar Alosaimi ◽  
Asif Naeem ◽  
Majed F. Alghoribi ◽  
Lilian Okdah ◽  
Maaweya E. Hamed ◽  
...  

In December 2019, the emergence of SARS-CoV-2 virus in China led to a pandemic. Since both Influenza Like Illness (ILI) and COVID-19 case definitions overlap, we re-investigated the ILI cases using PCR for the presence of SARS-CoV-2 in 739 nasopharyngeal swabs collected from November 2019 to March 2020. SARS-CoV-2 RNA was found in 37 samples (5%) collected mostly during February 2020. It was followed by confirmation of evolutionary and spatial relationships using next generation sequencing (NGS). We observed that the overall incidence of ILI cases during 2019–2020 influenza season was considerably higher than previous years and was gradually replaced with SARS-CoV-2, which indicated a silent transmission among ambulatory patients. Sequencing of representative isolates confirmed independent introductions and silent transmission earlier than previously thought. Evolutionary and spatial analyses revealed clustering in the GH clade, characterized by three amino acid substitutions in spike gene (D614G), RdRp (P323L) and NS3 (Q57H). P323L causes conformational change near nsp8 binding site that might affect virus replication and transcription. In conclusion, assessment of the community transmission among patients with mild COVID-19 illness, particularly those without epidemiological link for acquiring the virus, is of utmost importance to guide policy makers to optimize public health interventions. The detection of SARS-CoV-2 in ILI cases shows the importance of ILI surveillance systems and warrants its further strengthening to mitigate the ongoing transmission of SARS-CoV-2. The effect of NS3 substitutions on oligomerization or membrane channel function (intra- and extracellular) needs functional validation.


Genetics ◽  
2002 ◽  
Vol 162 (1) ◽  
pp. 395-411 ◽  
Author(s):  
Toby Johnson ◽  
Nick H Barton

Abstract We calculate the fixation probability of a beneficial allele that arises as the result of a unique mutation in an asexual population that is subject to recurrent deleterious mutation at rate U. Our analysis is an extension of previous works, which make a biologically restrictive assumption that selection against deleterious alleles is stronger than that on the beneficial allele of interest. We show that when selection against deleterious alleles is weak, beneficial alleles that confer a selective advantage that is small relative to U have greatly reduced probabilities of fixation. We discuss the consequences of this effect for the distribution of effects of alleles fixed during adaptation. We show that a selective sweep will increase the fixation probabilities of other beneficial mutations arising during some short interval afterward. We use the calculated fixation probabilities to estimate the expected rate of fitness improvement in an asexual population when beneficial alleles arise continually at some low rate proportional to U. We estimate the rate of mutation that is optimal in the sense that it maximizes this rate of fitness improvement. Again, this analysis relaxes the assumption made previously that selection against deleterious alleles is stronger than on beneficial alleles.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 871
Author(s):  
Swan Tan ◽  
Muhammad Farhan Sjaugi ◽  
Siew Chinn Fong ◽  
Li Chuin Chong ◽  
Hadia Syahirah Abd Raman ◽  
...  

Avian influenza virus A (H7N9), after circulating in avian hosts for decades, was identified as a human pathogen in 2013. Herein, amino acid substitutions possibly essential for human adaptation were identified by comparing the 4706 aligned overlapping nonamer position sequences (1–9, 2–10, etc.) of the reported 2014 and 2017 avian and human H7N9 datasets. The initial set of virus sequences (as of year 2014) exhibited a total of 109 avian-to-human (A2H) signature amino acid substitutions. Each represented the most prevalent substitution at a given avian virus nonamer position that was selectively adapted as the corresponding index (most prevalent sequence) of the human viruses. The majority of these avian substitutions were long-standing in the evolution of H7N9, and only 17 were first detected in 2013 as possibly essential for the initial human adaptation. Strikingly, continued evolution of the avian H7N9 virus has resulted in avian and human protein sequences that are almost identical. This rapid and continued adaptation of the avian H7N9 virus to the human host, with near identity of the avian and human viruses, is associated with increased human infection and a predicted greater risk of human-to-human transmission.


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