Records |
Author |
Peris, J.B.; Davis, P.; Cuevas, J.M.; Nebot, M.; Sanjuan, R. |
Title |
Distribution of Fitness Effects Caused by Single-Nucleotide Substitutions in Bacteriophage f1 |
Type |
Journal Article |
Year |
2010 |
Publication |
Genetics |
Abbreviated Journal |
Genetics |
Volume |
185 |
Issue |
2 |
Pages |
603-U308 |
Keywords |
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Abstract |
Empirical knowledge of the fitness effects of mutations is important for understanding many evolutionary processes, yet this knowledge is often hampered by several sources of measurement error and bias. Most of these problems can be solved using site-directed mutagenesis to engineer single mutations, an approach particularly suited for viruses due to their small genomes. Here, we used this technique to measure the fitness effect of 100 single-nucleotide substitutions in the bacteriophage f1, a filamentous single-strand DNA virus. We found that approximately one-fifth of all mutations are lethal. Viable ones reduced fitness by 11% on average and were accurately described by a log-normal distribution. More than 90% of synonymous substitutions were selectively neutral, while those affecting intergenic regions reduced fitness by 14% on average. Mutations leading to amino acid substitutions had an overall mean deleterious effect of 37%, which increased to 45% for those changing the amino acid polarity. Interestingly, mutations affecting early steps of the infection cycle tended to be more deleterious than those affecting late steps. Finally, we observed at least two beneficial mutations. Our results confirm that high mutational sensitivity is a general property of viruses with small genomes, including RNA and single-strand DNA viruses infecting animals, plants, and bacteria. |
Address |
[Peris, Joan B.; Davis, Paulina; Cuevas, Jose M.; Sanjuan, Rafael] Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolut, Valencia 46980, Spain, Email: rafael.sanjuan@uv.es |
Corporate Author |
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Thesis |
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Publisher |
Genetics Soc Am |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume ![sorted by Series Volume (numeric) field, ascending order (up)](img/sort_asc.gif) |
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Series Issue |
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Edition |
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ISSN |
0016-6731 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
ISI:000281905200017 |
Approved |
no |
Is ISI |
yes |
International Collaboration |
no |
Call Number |
IFIC @ elepoucu @ |
Serial |
383 |
Permanent link to this record |
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Author |
Sanjuan, R.; Nebot, M.; Chirico, N.; Mansky, L.M.; Belshaw, R. |
Title |
Viral Mutation Rates |
Type |
Journal Article |
Year |
2010 |
Publication |
Journal of Virology |
Abbreviated Journal |
J. Virol. |
Volume |
84 |
Issue |
19 |
Pages |
9733-9748 |
Keywords |
|
Abstract |
Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10(-8) to 10(-6) s/n/c for DNA viruses and from 10(-6) to 10(-4) s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at www.uv.es/rsanjuan/virmut. |
Address |
[Sanjuan, Rafael] Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolutiva, Dept Genet, Valencia 46980, Spain, Email: rafael.sanjuan@uv.es |
Corporate Author |
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Thesis |
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Publisher |
Amer Soc Microbiology |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Abbreviated Series Title |
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Series Volume ![sorted by Series Volume (numeric) field, ascending order (up)](img/sort_asc.gif) |
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Series Issue |
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Edition |
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ISSN |
0022-538x |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
ISI:000282641800008 |
Approved |
no |
Is ISI |
yes |
International Collaboration |
yes |
Call Number |
IFIC @ elepoucu @ |
Serial |
371 |
Permanent link to this record |
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Author |
Botella, F.J.; Branco, G.C.; Nebot, M.; Rebelo, M.N. |
Title |
Two-Higgs leptonic minimal flavour violation |
Type |
Journal Article |
Year |
2011 |
Publication |
Journal of High Energy Physics |
Abbreviated Journal |
J. High Energy Phys. |
Volume |
10 |
Issue |
10 |
Pages |
037 - 21pp |
Keywords |
Higgs Physics; Beyond Standard Model; Neutrino Physics |
Abstract |
We construct extensions of the Standard Model with two Higgs doublets, where there are flavour changing neutral currents both in the quark and leptonic sectors, with their strength fixed by the fermion mixing matrices V(CKM) and V(PMNS). These models are an extension to the leptonic sector of the class of models previously considered by Branco, Grimus and Lavoura, for the quark sector. We consider both the cases of Dirac and Majorana neutrinos and identify the minimal discrete symmetry required in order to implement the models in a natural way. |
Address |
[Botella, F. J.; Nebot, M.] Univ Valencia, Dept Fis Teor, CSIC, E-46100 Burjassot, Spain, Email: fbotella@uv.es |
Corporate Author |
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Thesis |
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Publisher |
Springer |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Abbreviated Series Title |
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Series Volume ![sorted by Series Volume (numeric) field, ascending order (up)](img/sort_asc.gif) |
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Series Issue |
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Edition |
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ISSN |
1126-6708 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
WOS:000296917100037 |
Approved |
no |
Is ISI |
yes |
International Collaboration |
yes |
Call Number |
IFIC @ pastor @ |
Serial |
830 |
Permanent link to this record |
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Author |
Botella, F.J.; Branco, G.C.; Nebot, M. |
Title |
The hunt for New Physics in the Flavour Sector with up vector-like quarks |
Type |
Journal Article |
Year |
2012 |
Publication |
Journal of High Energy Physics |
Abbreviated Journal |
J. High Energy Phys. |
Volume |
12 |
Issue |
12 |
Pages |
040 - 34pp |
Keywords |
Beyond Standard Model; Rare Decays; CP violation |
Abstract |
We analyse the possible presence of New Physics (NP) in the Flavour Sector and evaluate its potential for solving the tension between the experimental values of A(J/Psi KS) and Br(B+ -> tau(+)v(tau)) with respect to the Standard Model (SM) expectations. Updated model independent analyses, where NP contributions are allowed in B-d(0) – (B) over bar (0)(d) and B-s(0) – (B) over bar (0)(s) transitions, suggest the need of New Physics in the bd sector. A detailed analysis of recent Flavour data is then presented in the framework of a simple extension of the SM, where a Q = 2/3 vector-like isosinglet quark is added to the spectrum of the SM. Special emphasis is given to the implications of this model for correlations among various measurable quantities. We include constraints from all the relevant quark flavour sectors and give precise predictions for selected rare processes. We find important deviations from the SM in observables in the bd sector like the semileptonic asymmetry A(SL)(d), B-d(0) -> mu(+)mu(-) and A(SL)(s) – A(SL)(d). Other potential places where NP can show up include A(J/Psi Phi), gamma, K-L(0) -> pi(0)v (v) over bar, t -> Zq and D-0 -> mu(+)mu(-) among others. The experimental data favours in this model the existence of an up vector-like quark with a mass below 600(1000) GeV at 1(2) sigma. |
Address |
[Botella, F. J.; Nebot, M.] Univ Valencia, Dept Fis Teor, CSIC, E-46100 Burjassot, Spain, Email: fbotella@uv.es; |
Corporate Author |
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Thesis |
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Publisher |
Springer |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume ![sorted by Series Volume (numeric) field, ascending order (up)](img/sort_asc.gif) |
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Series Issue |
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Edition |
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ISSN |
1126-6708 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
WOS:000313123800040 |
Approved |
no |
Is ISI |
yes |
International Collaboration |
yes |
Call Number |
IFIC @ pastor @ |
Serial |
1344 |
Permanent link to this record |
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Author |
Sanjuan, R.; Nebot, M.; Peris, J.B.; Alcami, J. |
Title |
Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1 |
Type |
Journal Article |
Year |
2013 |
Publication |
Plos Biology |
Abbreviated Journal |
PLoS. Biol. |
Volume |
11 |
Issue |
4 |
Pages |
e1001523 - 10pp |
Keywords |
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Abstract |
The immune system should constitute a strong selective pressure promoting viral genetic diversity and evolution. However, HIV shows lower sequence variability at T-cell epitopes than elsewhere in the genome, in contrast with other human RNA viruses. Here, we propose that epitope conservation is a consequence of the particular interactions established between HIV and the immune system. On one hand, epitope recognition triggers an anti-HIV response mediated by cytotoxic T-lymphocytes (CTLs), but on the other hand, activation of CD4(+) helper T lymphocytes (T-H cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient level can promote either T-cell epitope conservation or escape. We predict greater conservation for epitopes contributing significantly to total immune activation levels (immunodominance), and when T-H cell infection is concomitant to epitope recognition (transinfection). We suggest that HIV-driven immune activation in the lymph nodes during the chronic stage of the disease may offer a favorable scenario for epitope conservation. Our results also support the view that some pathogens draw benefits from the immune response and suggest that vaccination strategies based on conserved T-H epitopes may be counterproductive. |
Address |
Univ Valencia, Inst Cavanilles Biodiversitat & Biol Evolut, Valencia, Spain, Email: rafael.sanjuan@uv.es |
Corporate Author |
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Thesis |
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Publisher |
Public Library Science |
Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume ![sorted by Series Volume (numeric) field, ascending order (up)](img/sort_asc.gif) |
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Series Issue |
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Edition |
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ISSN |
1545-7885 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
WOS:000318687800003 |
Approved |
no |
Is ISI |
yes |
International Collaboration |
no |
Call Number |
IFIC @ pastor @ |
Serial |
1446 |
Permanent link to this record |