Topological structure of the space of phenotypes: the case of rna neutral networks

Jacobo Aguirre, Javier M. Buldú, Michael Stich, Susanna C. Manrubia

Research output: Contribution to journalArticle

Abstract

The evolution and adaptation of molecular populations is constrained by the diversity accessible through mutational processes. RNA is a paradigmatic example of biopolymer where genotype (sequence) and phenotype (approximated by the secondary structure fold) are identified in a single molecule. The extreme redundancy of the genotype-phenotype map leads to large ensembles of RNA sequences that fold into the same secondary structure and can be connected through single-point mutations. These ensembles define neutral networks of phenotypes in sequence space. Here we analyze the topological properties of neutral networks formed by 12-nucleotides RNA sequences, obtained through the exhaustive folding of sequence space. A total of 4 12 sequences fragments into 645 subnetworks that correspond to 57 different secondary structures. The topological analysis reveals that each subnetwork is far from being random: it has a degree distribution with a well-defined average and a small dispersion, a high clustering coefficient, and an average shortest path between nodes close to its minimum possible value, i.e. the Hamming distance between sequences. RNA neutral networks are assortative due to the correlation in the composition of neighboring sequences, a feature that together with the symmetries inherent to the folding process explains the existence of communities. Several topological relationships can be analytically derived attending to structural restrictions and generic properties of the folding process. The average degree of these phenotypic networks grows logarithmically with their size, such that abundant phenotypes have the additional advantage of being more robust to mutations. This property prevents fragmentation of neutral networks and thus enhances the navigability of sequence space. In summary, RNA neutral networks show unique topological properties, unknown to other networks previously described.

Original languageEnglish
Article numbere26324
JournalPLoS ONE
Volume6
Issue number10
DOIs
Publication statusPublished - 18 Oct 2011

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RNA
Phenotype
phenotype
Genotype
nucleotide sequences
Biopolymers
Molecular Evolution
genotype
biopolymers
point mutation
Hamming distance
Point Mutation
Cluster Analysis
nucleotides
Redundancy
mutation
Nucleotides
Mutation
Molecules
Population

Bibliographical note

© 2011 Aguirre et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite this

Aguirre, Jacobo ; Buldú, Javier M. ; Stich, Michael ; Manrubia, Susanna C. / Topological structure of the space of phenotypes : the case of rna neutral networks. In: PLoS ONE. 2011 ; Vol. 6, No. 10.
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Topological structure of the space of phenotypes : the case of rna neutral networks. / Aguirre, Jacobo; Buldú, Javier M.; Stich, Michael; Manrubia, Susanna C.

In: PLoS ONE, Vol. 6, No. 10, e26324, 18.10.2011.

Research output: Contribution to journalArticle

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