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Research output: Contribution to Journal/Magazine › Journal article
Research output: Contribution to Journal/Magazine › Journal article
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TY - JOUR
T1 - Identification of important amino acid replacements in the 2013-2016 Ebola virus outbreak
AU - Olabode, Abayomi
AU - Gatherer, Derek
AU - Jiang, Xiaowei
AU - Matthews, David
AU - Hiscox, Julian
AU - Gunther, Stephan
AU - Carroll, Miles
AU - Lovell, Simon
AU - Robertson, David
PY - 2016/9/14
Y1 - 2016/9/14
N2 - The phylogenetic relationships of Zaire ebolavirus have been intensively analysed over the course of the 2013-2016 outbreak. However, there has been limited consideration of the functional impact of this variation. Here we describe an analysis of the available sequence data in the context of protein structure and phylogenetic history. Amino acid replacements are rare and predicted to have minor effects on protein stability. Synonymous mutations greatly outnumber nonsynonymous mutations, and most of the latter fall into unstructured intrinsically disordered regions, indicating that purifying selection is the dominant mode of selective pressure. However, one replacement, occurring early in the outbreak in Gueckedou in Guinea on 31st March 2014 (alanine to valine at position 82 in the GP protein), is close to the site where the virus binds to the host receptor NPC1 and is located in the phylogenetic tree at the origin of the major B lineage of the outbreak. The functional and evolutionary evidence indicates this A82V change likely has consequences for EBOV's host specificity and hence adaptation to humans.
AB - The phylogenetic relationships of Zaire ebolavirus have been intensively analysed over the course of the 2013-2016 outbreak. However, there has been limited consideration of the functional impact of this variation. Here we describe an analysis of the available sequence data in the context of protein structure and phylogenetic history. Amino acid replacements are rare and predicted to have minor effects on protein stability. Synonymous mutations greatly outnumber nonsynonymous mutations, and most of the latter fall into unstructured intrinsically disordered regions, indicating that purifying selection is the dominant mode of selective pressure. However, one replacement, occurring early in the outbreak in Gueckedou in Guinea on 31st March 2014 (alanine to valine at position 82 in the GP protein), is close to the site where the virus binds to the host receptor NPC1 and is located in the phylogenetic tree at the origin of the major B lineage of the outbreak. The functional and evolutionary evidence indicates this A82V change likely has consequences for EBOV's host specificity and hence adaptation to humans.
KW - Ebola
KW - Ebola virus disease
KW - EVD
KW - molecular evolution
KW - epidemiology
KW - bats
KW - Zaire ebolavirus
KW - protein
U2 - 10.1101/075168
DO - 10.1101/075168
M3 - Journal article
JO - Biorxiv
JF - Biorxiv
ER -