Topological structure of the space of phenotypes: the case of RNA neutral networks.

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 e...

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Autores principales:	Jacobo Aguirre, Javier M Buldú, Michael Stich, Susanna C Manrubia
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18880c933f0b4cdc89da74a7ae854fe7
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spelling	oai:doaj.org-article:18880c933f0b4cdc89da74a7ae854fe72021-11-18T07:36:17ZTopological structure of the space of phenotypes: the case of RNA neutral networks.1932-620310.1371/journal.pone.0026324https://doaj.org/article/18880c933f0b4cdc89da74a7ae854fe72011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028856/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Jacobo AguirreJavier M BuldúMichael StichSusanna C ManrubiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26324 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacobo Aguirre Javier M Buldú Michael Stich Susanna C Manrubia Topological structure of the space of phenotypes: the case of RNA neutral networks.
description	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.
format	article
author	Jacobo Aguirre Javier M Buldú Michael Stich Susanna C Manrubia
author_facet	Jacobo Aguirre Javier M Buldú Michael Stich Susanna C Manrubia
author_sort	Jacobo Aguirre
title	Topological structure of the space of phenotypes: the case of RNA neutral networks.
title_short	Topological structure of the space of phenotypes: the case of RNA neutral networks.
title_full	Topological structure of the space of phenotypes: the case of RNA neutral networks.
title_fullStr	Topological structure of the space of phenotypes: the case of RNA neutral networks.
title_full_unstemmed	Topological structure of the space of phenotypes: the case of RNA neutral networks.
title_sort	topological structure of the space of phenotypes: the case of rna neutral networks.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/18880c933f0b4cdc89da74a7ae854fe7
work_keys_str_mv	AT jacoboaguirre topologicalstructureofthespaceofphenotypesthecaseofrnaneutralnetworks AT javiermbuldu topologicalstructureofthespaceofphenotypesthecaseofrnaneutralnetworks AT michaelstich topologicalstructureofthespaceofphenotypesthecaseofrnaneutralnetworks AT susannacmanrubia topologicalstructureofthespaceofphenotypesthecaseofrnaneutralnetworks
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Topological structure of the space of phenotypes: the case of RNA neutral networks.

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