E. van Nimwegen Influenza escapes immunity along neutral networks. Science, 2006, 314(5807), 1884-1886.

ABSTRACT

In the late 1960s, Kimura made the then-revolutionary proposal that many amino acid substitutions are neutral in terms of evolutionary selection. There is now little doubt that essentially any genotype can undergo a substantial number of amino acid substitutions without substantially changing its fitness. This implies that there are large collections of selectively neutral genotypes that are connected through point mutations. Indeed, such “neutral networks” are observed in genotype-to-phenotype mappings of biomolecules. On page 1898 of this issue, Koelle et al. provide compelling evidence that neutral networks play a key role in the evolution of human influenza A (H3N2).

Computer simulations and analytical studies have shown that intertwined neutral networks have profound consequences for evolutionary adaptation. Evolving populations typically exhibit “epochs” of phenotypic stasis, punctuated by sudden changes in phenotype. However, phenotypic stasis is not accompanied by genotypic stasis. During each phenotypic epoch, the population is dominated by genotypes belonging to one neutral network, and neutral mutations cause the population to drift continuously through this neutral network (see the figure). Mutations to neighboring neutral networks (those networks that can be reached by a point mutation from one of the genotypes in the current neutral network) occur as well and enable the population to explore other phenotypes until, eventually, a mutant on a neutral network with higher fitness is generated. The offspring of this beneficial mutant will then spread through the population, causing a sudden shift in phenotype. Until the study by Koelle et al., this “epochal evolution” scenario (see the figure) had been observed mostly in silico and from in vitro evolution experiments.

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