scholarly journals Molecular Analysis of SARS-CoV-2 Genetic Lineages in Jordan: Tracking the Introduction and Spread of COVID-19 UK Variant of Concern at a Country Level

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 302
Author(s):  
Malik Sallam ◽  
Azmi Mahafzah
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Rapid Evolution ◽  
Molecular Signature ◽  
Special Focus ◽  
Genetic Lineage ◽  
Synonymous Mutation ◽  
Spike Gene ◽  
Genetic Lineages ◽  
The Uk

The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is manifested by the emergence of an ever-growing pool of genetic lineages. The aim of this study was to analyze the genetic variability of SARS-CoV-2 in Jordan, with a special focus on the UK variant of concern. A total of 579 SARS-CoV-2 sequences collected in Jordan were subjected to maximum likelihood and Bayesian phylogenetic analysis. Genetic lineage assignment was undertaken using the Pango system. Amino acid substitutions were investigated using the Protein Variation Effect Analyzer (PROVEAN) tool. A total of 19 different SARS-CoV-2 genetic lineages were detected, with the most frequent being the first Jordan lineage (B.1.1.312), first detected in August 2020 (n = 424, 73.2%). This was followed by the second Jordan lineage (B.1.36.10), first detected in September 2020 (n = 62, 10.7%), and the UK variant of concern (B.1.1.7; n = 36, 6.2%). In the spike gene region, the molecular signature for B.1.1.312 was the non-synonymous mutation A24432T resulting in a deleterious amino acid substitution (Q957L), while the molecular signature for B.1.36.10 was the synonymous mutation C22444T. Bayesian analysis revealed that the UK variant of concern (B.1.1.7) was introduced into Jordan in late November 2020 (mean estimate); four weeks earlier than its official reporting in the country. In Jordan, an exponential increase in COVID-19 cases due to B.1.1.7 lineage coincided with the new year 2021. The highest proportion of phylogenetic clustering was detected for the B.1.1.7 lineage. The amino acid substitution D614G in the spike glycoprotein was exclusively present in the country from July 2020 onwards. Two Jordanian lineages dominated infections in the country, with continuous introduction/emergence of new lineages. In Jordan, the rapid spread of the UK variant of concern should be monitored closely. The spread of SARS-CoV-2 mutants appeared to be related to the founder effect; nevertheless, the biological impact of certain mutations should be further investigated.

scholarly journals Targeted Recombination within the Spike Gene of Murine Coronavirus Mouse Hepatitis Virus-A59: Q159 Is a Determinant of Hepatotropism

1998 ◽  
Vol 72 (12) ◽  
pp. 9628-9636 ◽  
Author(s):  
Isabelle Leparc-Goffart ◽  
Susan T. Hingley ◽  
Ming Ming Chua ◽  
Joanna Phillips ◽  
Ehud Lavi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Spike Gene ◽  
Recombinant Viruses ◽  
Directed Mutation ◽  
Murine Coronavirus

ABSTRACT Previous studies of a group of mutants of the murine coronavirus mouse hepatitis virus (MHV)-A59, isolated from persistently infected glial cells, have shown a strong correlation between a Q159L amino acid substitution in the S1 subunit of the spike gene and a loss in the ability to induce hepatitis and demyelination. To determine if Q159L alone is sufficient to cause these altered pathogenic properties, targeted RNA recombination was used to introduce a Q159L amino acid substitution into the spike gene of MHV-A59. Recombination was carried out between the genome of a temperature-sensitive mutant of MHV-A59 (Alb4) and RNA transcribed from a plasmid (pFV1) containing the spike gene as well as downstream regions, through the 3′ end, of the MHV-A59 genome. We have selected and characterized two recombinant viruses containing Q159L. These recombinant viruses (159R36 and 159R40) replicate in the brains of C57BL/6 mice and induce encephalitis to a similar extent as wild-type MHV-A59. However, they exhibit a markedly reduced ability to replicate in the liver or produce hepatitis compared to wild-type MHV-A59. These viruses also exhibit reduced virulence and reduced demyelination. A recombinant virus containing the wild-type MHV-A59 spike gene, wtR10, behaved essentially like wild-type MHV-A59. This is the first report of the isolation of recombinant viruses containing a site-directed mutation, encoding an amino acid substitution, within the spike gene of any coronavirus. This technology will allow us to begin to map the molecular determinants of pathogenesis within the spike glycoprotein.

scholarly journals Rapid evolution of enhanced Zika virus virulence during direct vertebrate transmission chains

2020 ◽  
Author(s):  
Kasen K. Riemersma ◽  
Anna S. Jaeger ◽  
Chelsea M. Crooks ◽  
Katarina M. Braun ◽  
James Weger-Lucarelli ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Zika Virus ◽  
Rapid Evolution ◽  
Purifying Selection ◽  
Mammalian Host ◽  
Direct Transmission ◽  
Genetic Analyses ◽  
Vertebrate Hosts ◽  
The Impact

AbstractZika virus (ZIKV) has the unusual capacity to circumvent natural alternating mosquito-human transmission and be directly transmitted human-to-human via sexual and vertical routes. The impact of direct transmission on ZIKV evolution and adaptation to vertebrate hosts is unknown. Here we show that molecularly barcoded ZIKV rapidly adapted to a mammalian host during direct transmission chains in mice, coincident with the emergence of an amino acid substitution previously shown to enhance virulence. In contrast, little to no adaptation of ZIKV to mice was observed following chains of direct transmission in mosquitoes or alternating host transmission. Detailed genetic analyses revealed that ZIKV evolution in mice was generally more convergent and subjected to more relaxed purifying selection than in mosquitoes or alternate passages. These findings suggest that prevention of direct human transmission chains may be paramount to resist gains in ZIKV virulence.

Hubsm: A Novel Amino Acid Substitution Matrix for Comparing Hub Proteins

2017 ◽  
Vol 7 (8) ◽  
pp. 212
Author(s):  
Renganayaki G. ◽  
Achuthsankar S. Nair
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Low Complexity ◽  
Database Search ◽  
Substitution Matrix ◽  
Compositional Bias ◽  
Sequence Alignments ◽  
Amino Acid Substitution Matrix ◽  
Alignment Algorithms ◽  
Hub Proteins

Sequence alignment algorithms and  database search methods use BLOSUM and PAM substitution matrices constructed from general proteins. These de facto matrices are not optimal to align sequences accurately, for the proteins with markedly different compositional bias in the amino acid.   In this work, a new amino acid substitution matrix is calculated for the disorder and low complexity rich region of Hub proteins, based on residue characteristics. Insights into the amino acid background frequencies and the substitution scores obtained from the Hubsm unveils the  residue substitution patterns which differs from commonly used scoring matrices .When comparing the Hub protein sequences for detecting homologs,  the use of this Hubsm matrix yields better results than PAM and BLOSUM matrices. Usage of Hubsm matrix can be optimal in database search and for the construction of more accurate sequence alignments of Hub proteins.

scholarly journals A large compressibility change of protein induced by a single amino acid substitution

1996 ◽  
Vol 5 (3) ◽  
pp. 542-545 ◽  
Author(s):  
Kunihiko Gekko ◽  
Youjiro Tamura ◽  
Eiji Ohmae ◽  
Hideyuki Hayashi ◽  
Hiroyuki Kagamiyama ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid

Identification of a Functional Domain Within the Essential Core of Histone H3 That Is Required for Telomeric and HM Silencing in Saccharomyces cerevisiae

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 447-452 ◽  
Author(s):  
Jeffrey S Thompson ◽  
Marilyn L Snow ◽  
Summer Giles ◽  
Leslie E McPherson ◽  
Michael Grunstein
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Histone H3 ◽  
Single Amino Acid ◽  
Functional Domain ◽  
Partial Loss ◽  
Histone Fold ◽  
Gal1 Promoter ◽  
Substitution Mutations

Abstract Fourteen novel single-amino-acid substitution mutations in histone H3 that disrupt telomeric silencing in Saccharomyces cerevisiae were identified, 10 of which are clustered within the α1 helix and L1 loop of the essential histone fold. Several of these mutations cause derepression of silent mating locus HML, and an additional subset cause partial loss of basal repression at the GAL1 promoter. Our results identify a new domain within the essential core of histone H3 that is required for heterochromatin-mediated silencing.

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