The Evolutionary Interplay of Somatic and Germline Mutation Rates DOI
Annabel C. Beichman, Luke Zhu, Kelley Harris

et al.

Annual Review of Biomedical Data Science, Journal Year: 2024, Volume and Issue: 7(1), P. 83 - 105

Published: April 26, 2024

Novel sequencing technologies are making it increasingly possible to measure the mutation rates of somatic cell lineages. Accurate germline rate measurement have also been available for a decade, assess how this fundamental evolutionary parameter varies across tree life. Here, we review some classical theories about and evolution that were formulated using principles population genetics biology aging cancer. We find measurements, while still limited in phylogenetic diversity, seem consistent with theory selection preserve soma is proportional life span. However, make conflicting predictions regarding which species should most accurate DNA repair. Resolving conflict will require carefully measuring scale time division achieving better understanding pleiotropy among types.

Language: Английский

Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2 DOI Creative Commons

Ai Nguyen,

Huaying Zhao,

Dulguun Myagmarsuren

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 6, 2024

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage uniquely large genomic database SARS-CoV-2, we examine impact mutations across spectrum viable amino acid sequences on biophysical phenotypes highly expressed multifunctional nucleocapsid protein. We find variation in physicochemical parameters its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur related coronaviruses. In experiments with several N-protein species carrying associated major variants, point IDRs can have nonlocal modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, liquid-liquid phase separation. Omicron variant, distant different compensatory effects shifting delicate balance interactions controlling assembly properties, include creation new protein-protein interaction interface N-terminal IDR through defining P13L mutation. A picture emerges where genetic accompanied by significant characteristics species, particular IDRs.

Language: Английский

Citations

7
A specific phosphorylation-dependent conformational switch of SARS-CoV-2 nucleoprotein inhibits RNA binding DOI Creative Commons
Maiia Botova, Aldo R. Camacho‐Zarco, Jacqueline Tognetti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 23, 2024

Abstract The nucleoprotein (N) of SARS-CoV-2 encapsidates the viral genome and is essential for function. central disordered domain comprises a serine-arginine-rich (SR) that hyperphosphorylated in infected cells. This modification thought to regulate function N, although mechanistic details remain unknown. We use time-resolved NMR follow local long-range structural changes occurring during hyperphosphorylation by kinases SRPK1/GSK-3/CK1, thereby identifying conformational switch abolishes interaction with RNA. When 8 approximately uniformly-distributed sites are phosphorylated, SR competitively binds same interface as single-stranded RNA, resulting RNA binding inhibition. Phosphorylation PKA does not prevent binding, indicating pattern from physiologically-relevant specific Long-range contacts between RNA-binding, linker dimerization domains also abrogated, phenomena possibly related packaging unpackaging. study provides insight into recruitment host

Language: Английский

Citations

6
The effects of amino acid substitution of spike protein and genomic recombination on the evolution of SARS-CoV-2 DOI Creative Commons

Letian Fang,

Jie Xu,

Yue Zhao

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 25, 2023

Over three years’ pandemic of 2019 novel coronavirus disease (COVID-19), multiple variants and subvariants have emerged successively, outcompeted earlier become predominant. The sequential emergence reflects the evolutionary process mutation-selection-adaption severe acute respiratory syndrome 2 (SARS-CoV-2). Amino acid substitution/insertion/deletion in spike protein causes altered viral antigenicity, transmissibility, pathogenicity SARS-CoV-2. Early pandemic, D614G mutation conferred virus with advantages over previous increased it also laid a conservative background for subsequent substantial mutations. role genomic recombination evolution SARS-CoV-2 raised increasing concern occurrence recombinants such as Deltacron, XBB.1.5, XBB.1.9.1, XBB.1.16 late phase pandemic. Co-circulation different co-infection immunocompromised patients accelerate recombinants. Surveillance variations, particularly recombination, is essential to identify ongoing changes genome antigenic epitopes thus leads development new vaccine strategies interventions.

Language: Английский

Citations

14
Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2 DOI Creative Commons

Ai Nguyen,

Huaying Zhao,

Dulguun Myagmarsuren

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: June 28, 2024

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage uniquely large genomic database SARS-CoV-2, we examine impact mutations across spectrum viable amino acid sequences on biophysical phenotypes highly expressed multifunctional nucleocapsid protein. We find variation in physicochemical parameters its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur related coronaviruses. In experiments with several N-protein species carrying associated major variants, point IDRs can have nonlocal modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, liquid-liquid phase separation. Omicron variant, distant different compensatory effects shifting delicate balance interactions controlling assembly properties, include creation new protein-protein interaction interface N-terminal IDR through defining P13L mutation. A picture emerges where genetic accompanied by significant characteristics species, particular IDRs.

Language: Английский

Citations

5
A specific phosphorylation-dependent conformational switch in SARS-CoV-2 nucleocapsid protein inhibits RNA binding DOI Creative Commons
Maiia Botova, Aldo R. Camacho‐Zarco, Jacqueline Tognetti

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(31)

Published: Aug. 2, 2024

The nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 encapsidates the viral genome and is essential for function. central disordered domain comprises a serine-arginine-rich (SR) region that hyperphosphorylated in infected cells. This modification regulates function, although mechanistic details remain unknown. We use nuclear magnetic resonance to follow structural changes occurring during hyperphosphorylation by serine arginine kinase 1, glycogen synthase 3, casein abolishes interaction with RNA. When eight approximately uniformly distributed sites have been phosphorylated, SR binds same interface as single-stranded RNA, resulting complete inhibition RNA binding. Phosphorylation A does not prevent binding, indicating pattern from physiologically relevant kinases specific inhibition. Long-range contacts between linker, dimerization domains are abrogated, phenomena possibly related packaging unpackaging. study provides insight into recruitment host regulate

Language: Английский

Citations

5
Role of N343 glycosylation on the SARS-CoV-2 S RBD structure and co-receptor binding across variants of concern DOI Creative Commons
Callum M. Ives, Linh Nguyen, Carl A. Fogarty

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: March 27, 2024

Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both evasion and fitness. Successful variations in glycan shield are difficult to achieve though, as glycosylation is also critical folding structural stability. Within this framework, identification sites that structurally dispensable can provide insight into evolutionary mechanisms inform immune surveillance. In work, we show through over 45 μs cumulative sampling from conventional enhanced molecular dynamics (MD) simulations, how structure immunodominant S receptor binding domain (RBD) regulated by N -glycosylation at N343 glycan’s role changes WHu-1, alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), omicron (BA.1 BA.2.86) variants. More specifically, find amphipathic nature -glycan instrumental preserve integrity RBD hydrophobic core loss triggers specific consistent conformational change. We change allosterically regulates conformation motif (RBM) alpha, RBDs, but not variants, due mutations reinforce architecture. support these findings, monosialylated ganglioside co-receptors highly dependent on RBD, affinity significantly across VoCs. Ultimately, functional work reinforces our understanding function allows us identify constraints within which site become hotspot shield.

Language: Английский

Citations

4
Emergence of SARS-CoV-2 Omicron Variant JN.1 in Tamil Nadu, India - Clinical Characteristics and Novel Mutations DOI Creative Commons

Sivaprakasam T. Selvavinayagam,

Sathish Sankar, Yean K. Yong

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 22, 2024

Abstract In December 2023, we observed a notable shift in the COVID-19 landscape, when JN.1 emerged as predominant SARS-CoV-2 variant with 95% incidence. We characterized clinical profile, and genetic changes JN.1, an emerging of interest. Whole genome sequencing was performed on positive samples, followed by sequence analysis. Mutations within spike protein sequences were analyzed compared previous lineages sublineages SARS-CoV-2, to identify potential impact these unique mutations structure possible functionality. Several dynamic identified herein. Our data provides key insights into emergence newer variants our region highlights need for robust sustained genomic surveillance SARS-CoV-2.

Language: Английский

Citations

4
C→U transition biases in SARS-CoV-2: still rampant 4 years from the start of the COVID-19 pandemic DOI Creative Commons
Peter Simmonds

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

ABSTRACT The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has been characterized by rapid adaptive changes that confer immune escape enhanced human-to-human transmissibility. Sequence change is additionally marked an excess number C→U transitions suggested as being due to host-mediated genome editing. To investigate how these influence evolutionary trajectory SARS-CoV-2, 2,000 high-quality, coding complete sequences SARS-CoV-2 variants collected pre-September 2020 from each subsequently appearing alpha, delta, BA.1, BA.2, BA.5, XBB, EG, HK, JN.1 lineages were downloaded NCBI Virus April 2024. most common substitution during diversification over 4-year observation period. A net loss C bases accumulation U’s occurred at a constant rate approximately 0.2%–0.25%/decade. quarter all sites with (26.5%; range 20.0%–37.2%) around five times more than observed for other (5.3%–6.8%). In contrast random distribution across genome, substitutions statistically preferred lineage. However, only polymorphic showed evidence 5′U context previously associated APOBEC 3A There was similarly weak preference unpaired suggesting much less stringent targeting RNA mediated A3 deaminases DNA Future functional studies are required determine editing preferences, impacts on replication fitness vivo viruses, impact host tropism. IMPORTANCE Severe shown remarkable capacity adapt evade human responses increase its also increasingly scarred effects multiple mutations cellular defense mechanism akin restriction factors retroviruses. Through analysis large data sets isolate throughout period beyond, we show have driven base compositional time amounting Most absence upstream-base or protein, 3A. analyses provide series testable hypotheses can be experimentally investigated future.

Language: Английский

Citations

4
Adaptive evolution of SARS-CoV-2 during a persistent infection for 521 days in an immunocompromised patient DOI Creative Commons
Hanno Schmidt, Luca Aroha Schick, Jürgen Podlech

et al.

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 17, 2025

Immunocompromised patients struggle to adequately clear viral infections, offering the virus opportunity adapt immune system in host. Here we present a case study of patient undergoing allogeneic hematopoietic stem cell transplantation with 521-day follow-up SARS-CoV-2 infection BF.7.21 variant. Virus samples from five time points were submitted whole genome sequencing. Between first detection and its clearance, patient's population acquired 34 amino acid substitutions 8 deletions coding regions. With 11 receptor binding domain virus' spike protein, 15 times more abundant than expected for random distribution this highly functional region. Amongst them S:K417T, S:N440S, S:K444R, S:V445A, S:G446N, S:L452Q, S:N460K, S:E484V at positions that are notorious their resistance-mediating effects. The substitution patterns found indicate ongoing adaptive evolution.

Language: Английский

Citations

0
An expanding universe of mutational signatures and its rapid evolution in single-stranded RNA viruses DOI Creative Commons
Yue Yang, Xinyi Zhang, Tingting Chen

et al.

Molecular Biology and Evolution, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array endogenous and exogenous factors associated with changes. However, the overall landscape germline mutations across tree life evolutionary driving forces are rather unclear. In this study, we analyzed single-stranded RNA (ssRNA) viruses which known to jump between different hosts divergent environments. We found that spectra ssRNA differ significantly mainly their genetic divergence. Surprisingly, host environments contribute much less spectrum, challenging prevailing view cellular environment is major determinant spectrum viruses. To dissect shaping viral spectra, selected two important scenarios, namely inter-host evolution strains as well intra-host evolution. both change through space time, strongly correlating levels natural selection. Combining all viruses, identified suite signatures varying degrees similarity humans, indicating universal life. Taken together, unraveled an unprecedented dynamic pinpointing fast species.

Language: Английский

Citations

0