Elife
 2018
DOI: 10.7554/elife.34420
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Mapping mutational effects along the evolutionary landscape of HIV envelope

Hugh K. Haddox
1
,
Adam S. Dingens
2
,
Sarah K. Hilton
3
et al.

Abstract: The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at >100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted… Show more

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Cited by 143 publications

(197 citation statements)
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“…Therefore, positive and negative shifts do not tend to be associated with the locations of sites in a protein. Our conclusions are consistent with experimental results in the HIV envelope protein where sites with shifted propensities were observed across the protein ( Haddox et al 2018 ).…”
Section: Resultssupporting
confidence: 92%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…Therefore, positive and negative shifts do not tend to be associated with the locations of sites in a protein. Our conclusions are consistent with experimental results in the HIV envelope protein where sites with shifted propensities were observed across the protein ( Haddox et al 2018 ).…”
Section: Resultssupporting
confidence: 92%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…Consistency across three biological replicates was assessed using Spearman correlation coefficients between each post-selection replicate and the merged pre-selection dataset. We observed moderate to high reproducibility between replicates (LAI ρ = 0.46–0.65, Supplementary Figure 1A), consistent with previous gene-wide DMS analyses (46, 62), suggesting that replicate selections were subject to similar selective pressures.…”
Section: Resultssupporting
confidence: 89%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
“…2). In summary, our results are in line with observations from other studies where the same mutation led to different phenotypes when introduced into homologous proteins (KONDRASHOV et al 2002;LUNZER et al 2010;NATARAJAN et al 2013;VIKTOROVSKAYA et al 2013;DOUD et al 2015;STARR AND THORNTON 2016;HADDOX et al 2018;PARK et al 2022), highlighting the divergent nature of epistasis networks in highly conserved proteins like msRNAPs. Even considering our above findings, our experiments here provide case studies for examples of complex interactions during evolutionary divergence.…”
Section: Discussionsupporting
confidence: 92%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
show abstract
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