Stability-mediated epistasis constrains the evolution of an influenza protein.

John Maynard Smith compared protein evolution to the game where one word is converted into another a single letter at a time, with the constraint that all intermediates are words: WORD→WORE→GORE→GONE→GENE. In this analogy, epistasis constrains evolution, with some mutations tolerated only after the occurrence of others. To test whether epistasis similarly constrains actual protein evolution, we created all intermediates along a 39-mutation evolutionary trajectory of influenza nucleoprotein, and also introduced each mutation individually into the parent. Several mutations were deleterious to the parent despite becoming fixed during evolution without negative impact. These mutations were destabilizing, and were preceded or accompanied by stabilizing mutations that alleviated their adverse effects. The constrained mutations occurred at sites enriched in T-cell epitopes, suggesting they promote viral immune escape. Our results paint a coherent portrait of epistasis during nucleoprotein evolution, with stabilizing mutations permitting otherwise inaccessible destabilizing mutations which are sometimes of adaptive value. DOI:http://dx.doi.org/10.7554/eLife.00631.001

Neutral genetic drift can aid functional protein evolution

BACKGROUND: Many of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve when selection begins to favor other, "promiscuous" functions that are incidental to a protein's biological role. If mutations that are neutral with respect to a protein's primary biological function cause substantial changes in promiscuous functions, these mutations could enable future functional evolution. RESULTS: Here we investigate this possibility experimentally by examining how cytochrome P450 enzymes that have evolved neutrally with respect to activity on a single substrate have changed in their abilities to catalyze reactions on five other substrates. We find that the enzymes have sometimes changed as much as four-fold in the promiscuous activities. The changes in promiscuous activities tend to increase with the number of mutations, and can be largely rationalized in terms of the chemical structures of the substrates. The activities on chemically similar substrates tend to change in a coordinated fashion, potentially providing a route for systematically predicting the change in one function based on the measurement of several others. CONCLUSIONS: Our work suggests that initially neutral genetic drift can lead to substantial changes in protein functions that are not currently under selection, in effect poising the proteins to more readily undergo functional evolution should selection "ask new questions" in the future

Magnetic susceptibility of vanadium carbide

Magnetic susceptibility of vanadium carbide from 77 to 300 K measured by magnetomete

The impact of health on professionally active people's incomes in Poland. Microeconometric analysis

The outcome of the research confirms the occurrence of positive interaction between professionally active people's incomes and the self-assessed state of health. People declaring a bad state of health have incomes by 20% on average lower than people who enjoy good health (assuming that the remaining characteristics of the surveyed person are the same). In case of men, the impact of health state on incomes is slightly greater than in case of women.Wyniki badań potwierdzają istnienie pozytywnej zależności dochodów osób aktywnych zawodowo od stanu zdrowia mierzonego jego samooceną. Osoby deklarujące zły stan zdrowia osiągają dochody przeciętnie o 20% niższe niż osoby, które cieszą się dobrym stanem zdrowia (przy założeniu, że pozostałe charakterystyki badanej osoby są takie same). W przypadku mężczyzn zależność dochodów od stanu zdrowia jest nieznacznie silniejsza niż w przypadku kobiet

Acronyms, abbreviations and initialisms

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73192/1/j.1464-410x.2000.00717.x.pd

The Discovery of Vibrationally-Excited H_2 in the Molecular Cloud near GRB 080607

GRB 080607 has provided the first strong observational signatures of molecular absorption bands toward any galaxy hosting a gamma-ray burst. Despite the identification of dozens of features as belonging to various atomic and molecular (H_2 and CO) carriers, many more absorption features remained unidentified. Here we report on a search among these features for absorption from vibrationally-excited H_2, a species that was predicted to be produced by the UV flash of a GRB impinging on a molecular cloud. Following a detailed comparison between our spectroscopy and static, as well as dynamic, models of H_2* absorption, we conclude that a column density of 10^{17.5+-0.2} cm^{-2} of H_2* was produced along the line of sight toward GRB 080607. Depending on the assumed amount of dust extinction between the molecular cloud and the GRB, the model distance between the two is found to be in the range 230--940 pc. Such a range is consistent with a conservative lower limit of 100 pc estimated from the presence of Mg I in the same data. These distances show that substantial molecular material is found within hundreds of pc from GRB 080607, part of the distribution of clouds within the GRB host galaxy.Comment: Submitted to ApJL, 6 pages emulate