Miguel Nebot

Viral Mutation Rates

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 to10−6 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 .

Distribution of Fitness Effects Caused by Single-nucleotide Substitutions in Bacteriophage f1

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.

New Physics and Evidence for a Complex CKM

We carefully analyse the present experimental evidence for a com- plex CKM matrix, even allowing for New Physics contributions to ǫK, a J/�KS , �MBd , �MBs , and theI = 1/2 piece of B → ρρ and B → ρπ. We emphasize the crucial role played by the angle γ in both providing irrefutable evidence for a complex CKM matrix and placing constraints on the size of NP contributions. It is shown that even if one allows for New Physics a real CKM matrix is excluded at a 99.92% C.L., and the probability for the phase γ to be in the interval (−170 ◦ ; −10 ◦ ) ∪ (10 ◦ ;170 ◦ ) is 99.7%.

The Zee–Babu model revisited in the light of new data

We update previous analyses of the Zee–Babu model in the light of new data, e.g., the mixing angle θ13, the rare decay μ → eγ and the LHC results. We also analyze the possibility of accommodating the deviations in Γ( H → γγ) hinted by the LHC experiments, and the stability of the scalar potential. We find that neutrino oscillation data and low energy constraints are still compatible with masses of the extra charged scalars accessible to LHC. Moreover, if any of them is discovered, the model can be falsified by combining the information on the singly and doubly charged scalar decay modes with neutrino data. Conversely, if the neutrino spectrum is found to be inverted and the CP phase δ is quite different from π , the masses of the charged scalars will be well outside the LHC reach.

A Network Model for the Correlation between Epistasis and Genomic Complexity

The study of genetic interactions (epistasis) is central to the understanding of genome organization and evolution. A general correlation between epistasis and genomic complexity has been recently shown, such that in simpler genomes epistasis is antagonistic on average (mutational effects tend to cancel each other out), whereas a transition towards synergistic epistasis occurs in more complex genomes (mutational effects strengthen each other). Here, we use a simple network model to identify basic features explaining this correlation. We show that, in small networks with multifunctional nodes, lack of redundancy, and absence of alternative pathways, epistasis is antagonistic on average. In contrast, lack of multi-functionality, high connectivity, and redundancy favor synergistic epistasis. Moreover, we confirm the previous finding that epistasis is a covariate of mutational robustness: in less robust networks it tends to be antagonistic whereas in more robust networks it tends to be synergistic. We argue that network features associated with antagonistic epistasis are typically found in simple genomes, such as those of viruses and bacteria, whereas the features associated with synergistic epistasis are more extensively exploited by higher eukaryotes.

The hunt for New Physics in the Flavour Sector with up vector-like quarks

A bstractWe 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

Two-Higgs leptonic minimal flavour violation

{A_{{J/\varPsi {K_S}}}}

Invariant approach to flavour-dependent CP-violating phases in the MSSM

and

Unitarity triangles and the search for New Physics

\mathrm{Br}\left( {{B^{+}}\to {\tau^{+}}{\nu_{\tau }}} \right)

CP violation and limits on New Physics including recent Bs measurements

with respect to the Standard Model (SM) expectations. Updated model independent analyses, where NP contributions are allowed in