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The architecture of an empirical genotype-phenotype map

The architecture of an empirical genotype-phenotype map
The architecture of an empirical genotype-phenotype map

Recent advances in high-throughput technologies are bringing the study of empirical genotype-phenotype (GP) maps to the fore. Here, we use data from protein-binding microarrays to study an empirical GP map of transcription factor (TF) -binding preferences. In this map, each genotype is a DNA sequence. The phenotype of this DNA sequence is its ability to bind one or more TFs. We study this GP map using genotype networks, in which nodes represent genotypes with the same phenotype, and edges connect nodes if their genotypes differ by a single small mutation. We describe the structure and arrangement of genotype networks within the space of all possible binding sites for 525 TFs from three eukaryotic species encompassing three kingdoms of life (animal, plant, and fungi). We thus provide a high-resolution depiction of the architecture of an empirical GP map. Among a number of findings, we show that these genotype networks are "small-world" and assortative, and that they ubiquitously overlap and interface with one another. We also use polymorphism data from Arabidopsis thaliana to show how genotype network structure influences the evolution of TF-binding sites in vivo. We discuss our findings in the context of regulatory evolution.

Evolvability, Molecular evolution, Mutations, Transcription factors
0014-3820
Aguilar-Rodríguez, José
120e28d4-bb3a-4a22-9e74-a13750b802e9
Peel, Leto
502a7ee9-369e-4b4e-8a75-d1e8d97896e1
Stella, Massimo
37822c93-2522-4bc0-b840-ca32c75efbd7
Wagner, Andreas
e80cb93f-a8d7-44f9-b013-2c5621430124
Payne, Joshua L.
4d990a3c-504b-4a15-936a-9fddcd105467
Aguilar-Rodríguez, José
120e28d4-bb3a-4a22-9e74-a13750b802e9
Peel, Leto
502a7ee9-369e-4b4e-8a75-d1e8d97896e1
Stella, Massimo
37822c93-2522-4bc0-b840-ca32c75efbd7
Wagner, Andreas
e80cb93f-a8d7-44f9-b013-2c5621430124
Payne, Joshua L.
4d990a3c-504b-4a15-936a-9fddcd105467

Aguilar-Rodríguez, José, Peel, Leto, Stella, Massimo, Wagner, Andreas and Payne, Joshua L. (2018) The architecture of an empirical genotype-phenotype map. Evolution. (doi:10.1111/evo.13487).

Record type: Article

Abstract

Recent advances in high-throughput technologies are bringing the study of empirical genotype-phenotype (GP) maps to the fore. Here, we use data from protein-binding microarrays to study an empirical GP map of transcription factor (TF) -binding preferences. In this map, each genotype is a DNA sequence. The phenotype of this DNA sequence is its ability to bind one or more TFs. We study this GP map using genotype networks, in which nodes represent genotypes with the same phenotype, and edges connect nodes if their genotypes differ by a single small mutation. We describe the structure and arrangement of genotype networks within the space of all possible binding sites for 525 TFs from three eukaryotic species encompassing three kingdoms of life (animal, plant, and fungi). We thus provide a high-resolution depiction of the architecture of an empirical GP map. Among a number of findings, we show that these genotype networks are "small-world" and assortative, and that they ubiquitously overlap and interface with one another. We also use polymorphism data from Arabidopsis thaliana to show how genotype network structure influences the evolution of TF-binding sites in vivo. We discuss our findings in the context of regulatory evolution.

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Accepted/In Press date: 3 April 2018
e-pub ahead of print date: 20 April 2018
Keywords: Evolvability, Molecular evolution, Mutations, Transcription factors

Identifiers

Local EPrints ID: 421461
URI: http://eprints.soton.ac.uk/id/eprint/421461
ISSN: 0014-3820
PURE UUID: d7c77903-0b70-4152-ac8a-cdebf1e867ee

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Date deposited: 13 Jun 2018 16:30
Last modified: 16 Dec 2019 18:09

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