Un concepto importante en evolución de virus cumple 30 años

En breve se cumplirán 30 años de la publicación de lo que los anglosajones denominan un artículo seminal, un descubrimiento que abrió una línea de conocimiento impresionante. El artículo en cuestión, un Cell del año 1978, está enlazado aquí, y el resumen es:

Nucleotide sequence heterogeneity of an RNA phage population
Esteban Domingo*, Donna Sabo†, Tadatsugu Taniguchi and Charles Weissmann
Institut für Molekularbiologie I Universität Zürich Hönggerberg 8093, Zürich, Switzerland
Received 19 December 1977. Available online 26 April 2004.
Abstract
The nucleotide sequence of 32P-RNA from Qβ phage clones was sampled by two-dimensional polyacrylamide gel electrophoresis of the RNAase T1-resistant oligonucleotides (T1 fingerprinting). About 15% of the clones derived from a multiply passaged Qβ population showed fingerprint patterns which deviated from that of the RNA from the total population. All deviations examined could be attributed to one and, less frequently, to two or more nucleotide transitions. Since the fingerprinting technique allows the analysis of only about 10% of the RNA sequence, we estimate that each viable phage genome in a multiply passaged population differs in one to two positions from the “average” sequence of the parental population. Several deviant clones were tested by growth competition against a “wild-type” population; after 10–20 generations, the resulting phage showed the “wild-type” T1 fingerprint pattern. We propose that a Qβ phage population is in a dynamic equilibrium, with viable mutants arising at a high rate (Batschelet, Domingo and Weissmann, 1976; Domingo, Flavell and Weissmann, 1976) on the one hand, and being strongly selected against on the other. The genome of Qβ phage cannot be described as a defined unique structure, but rather as a weighted average of a large number of different individual sequences.


La importancia de este artículo radica en la aplicación práctica de un concepto totalmente teórico y especulativo, cuasiespecie, desarrollado por Manfred Eigen para intentar explicar como serían las poblaciones de elementos replicantes prebióticas.

Me gusta particularmemnte este párrafo de la discusión:
"It is of interest to note that if members of an equilibrium population deviate, on the average, in two positions from the “wild-type” sequence, then only 14% of the population consists of “wild-type” phage. For three and five deviations per strand, this value drops to 5% and 2%, respectively. One thus arrives at the concept of a phage genome which is statistically defined but individually indeterminate insofar as most of the individuals differ in a few positions from the average sequence. On the basis of theoretical considerations, M. Eigen (personal communication) has predicted this situation and coined the term “quasi-species” to describe such a population. Heterogeneous populations of this kind should be capable of rapid adaptation to a changing environment, not only because of the high mutation rate, but also because of the presence of a large proportion of variants. If each particle of an RNA phage population of 10” members contains an average of two nucleotide substitutions, then the number of particles with one, two, three and four nucleotide transitions will be 2.7 xE10, 2.7 x E10, 1.8 x E10 and 0.9 x E10, respectively, as given by a Poisson distribution. Since the number of different RNAs with one, two, three and four transitions are 4.5 x E3, 1 x E7, 1.5 X E10 and 1.7 x E13, it is clear that all possible single, double and triple transition mutants, as well as about 0.05% of the quadruple mutants, preexist in the population."

Y lo mejor de todo. Tenemos la suerte de tener muy cerca al primer firmante, hoy profesor de investigación del CSIC. La página web de su grupo, aquí.