Proteome-Wide Structural Computations Provide Insights into Empirical Amino Acid Substitution Matrices

The relative contribution of mutation and selection to the amino acid substitution rates observed in empirical matrices is unclear. Herein, we present a neutral continuous fitness-stability model, inspired by the Arrhenius law (qij=aije−|ΔΔGij| ). The model postulates that the rate of amino acid substitution (i→j ) is determined by the product of a pre-exponential factor, which is influenced by the genetic code structure, and an exponential term reflecting the relative fitness of the amino acid substitutions. To assess the validity of our model, we computed changes in stability of 14,094 proteins, for which 137,073,638 in silico mutants were analyzed. These site-specific data were summarized into a 20 square matrix, whose entries, |ΔΔGij| , were obtained after averaging through all the sites in all the proteins. We found a significant positive correlation between these energy values and the disease-causing potential of each substitution, suggesting that the exponential term accurately summarizes the fitness effect. A remarkable observation was that amino acids that were highly destabilizing when acting as the source, tended to have little effect when acting as the destination, and vice versa (source → destination). The Arrhenius model accurately reproduced the pattern of substitution rates collected in the empirical matrices, suggesting a relevant role for the genetic code structure and a tuning role for purifying selection exerted via protein stability.Partial funding for open access charge: Universidad de Málag

Algunas curiosidades sobre la vida y la muerte

I don’t remember how old I was when I became aware that I was suffering from a sexually transmitted disease that was fatal. Although this disease is asymptomatic in the early years, it gradually develops until it inevitably ends in deathNo recuerdo la edad que tendría cuando tomé conciencia de que padecía una enfermedad mortal de  transmisión sexual. Aunque durante los primeros años esta enfermedad cursa de forma asintomática, poco a poco va desarrollándose hasta acabar, inevitablemente, en la muerte.&nbsp

Daniel E. Koshland Jr. Una historia con pantalones tejanos, un pingüino y mucha ciencia

Escribía Cervantes que «en mucho más se ha de estimar un diente que un diamante». Enseñanzas de este tenor justificaban, a criterio del desaparecido diario El Sol, la decisión ministerial de imponer vía decreto la lectura del Quijote en las escuelas. Esto, acontecía en España en marzo de 1920. En estas mismas fechas, pero al otro lado del Atlántico, venía al mundo en la ciudad de Nueva York nuestro protagonista, Daniel E. Koshland Jr., en el seno de una familia judía

Democracia animal: una cuestión de vida o muerte

Imagine el lector por un momento algún frondoso rincón en un bosque. Para completar tan bucólico cuadro, añadamos ahora una plácida manada de ciervos rojos. ¿Dije plácida? Bueno, eso fue en el instante anterior, porque ahora de forma súbita, y sin que haya una causa aparente, todos los animales se ponen apresuradamente en marcha para abandonar nuestro imaginado escenario. ¿Qué es lo que ha ocurrido

La vida inmortal de Henrietta Lacks o la historia de las células HeLa

Encounters in Biology”, tribute has been paid to scientists of immense stature such as Charles Darwin or Alexander von Humboldt. These characters arouse our admiration, not only for their important contributions to collective knowledge, but also for the “genius” aspects of their lives. However, we cannot ignore that Science is nourished by various sources, with genius being the rarest. Hard and discreet work, well-understood competitiveness, healthy collaboration, social context, and even strokes of luck, are all factors that influence the advancement of scientific knowledge. Today, as I write this, is World Cancer Day. For all these reasons, I thought it appropriate to pay a modest tribute to a woman whose name destiny wanted to inscribe in the annals of the fight against cancer, and of Biology in general.Desde las páginas de Encuentros en la Biología se ha homenajeado a científicos de inmensa talla como Charles Darwin o Alexander von Humboldt. Estos personajes suscitan nuestra admiración, no sólo por sus importantes contribuciones al conocimiento colectivo, sino también por lo que de “genial” tuvieron sus vidas. Sin embargo, no podemos ignorar que la Ciencia se nutre de diversas fuentes, siendo el genio la más rara. El trabajo arduo y discreto, la competitividad bien entendida, la sana colaboración, el contexto social e incluso los golpes de suerte, son todos ellos factores que influyen en el avance del conocimiento científico. Hoy, cuando escribo esto, es el día mundial contra el cáncer. Por todo ello, me ha parecido oportuno rendir un modesto homenaje a una mujer cuyo nombre quiso el destino inscribir en los anales de la lucha contra el cáncer, y de la Biología en general

On the Relationships of Postcanine Tooth Size with Dietary Quality and Brain Volume in Primates: Implications for Hominin Evolution

Brain volume and cheek-tooth size have traditionally been considered as two traits that show opposite evolutionary trends during the evolution of Homo. As a result, differences in encephalization and molarization among hominins tend to be interpreted in paleobiological grounds, because both traits were presumably linked to the dietary quality of extinct species. Here we show that there is an essential difference between the genus Homo and the living primate species, because postcanine tooth size and brain volume are related to negative allometry in primates and show an inverse relationship in Homo. However, when size effects are removed, the negative relationship between encephalization and molarization holds only for platyrrhines and the genus Homo. In addition, there is no general trend for the relationship between postcanine tooth size and dietary quality among the living primates. If size and phylogeny effects are both removed, this relationship vanishes in many taxonomic groups. As a result, the suggestion that the presence of well-developed postcanine teeth in extinct hominins should be indicative of a poor-quality diet cannot be generalized to all extant and extinct primates.This research has been funded by the Spanish Ministry of Science and Innovation (Projects CGL2010-18124, CGL2011-30334, and HAR2008-04577) and supported by the Department of Economy, Innovation and Science, Junta de Andalucía, Spain (Project P11-HUM-7248 and Research Groups HUM-607 and RNM-146)