An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors

Miguel Angel Fuertes; Carlos Alonso

doi:doi:10.11648/j.eeb.20210603.11

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An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors

Miguel Angel Fuertes, Carlos Alonso

Published in Ecology and Evolutionary Biology (Volume 6, Issue 3)

Received: 24 April 2021 Accepted: 11 May 2021 Published: 13 July 2021

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Abstract

Capturing conserved patterns in genes and proteins is important for inferring phenotype prediction and evolutionary analysis. The study is focused on the conserved patterns of the G protein-coupled receptors, an important superfamily of receptors. Olfactory receptors represent more than 2% of our genome and constitute the largest family of G protein-coupled receptors, a key class of drug targets. As no crystallographic structures are available, mechanistic studies rely on the use of molecular dynamic modelling combined with site-directed mutagenesis data. In this paper, we hypothesized that human-mouse orthologs coding for G protein-coupled receptors maintain, at speciation events, shared compositional structures independent, to some extent, of their percent identity as reveals a method based in the categorization of nucleotide triplets by their gross composition. The data support the consistency of the hypothesis, showing in ortholog G protein-coupled receptors the presence of emergent shared compositional structures preserved at speciation events. An extreme bias in synonymous codon usage is observed in both the conserved and non-conserved regions of many of these receptors that could be potentially relevant in codon optimization studies. The analysis of their compositional structures would help to design new evolutionary based strategies for rational mutations that would aid to understand the characteristics of individual G protein-coupled receptors, their subfamilies and the role in many physiological and pathological processes, supplying new possible drug targets.

Published in	Ecology and Evolutionary Biology (Volume 6, Issue 3)
DOI	10.11648/j.eeb.20210603.11
Page(s)	53-77
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2021. Published by Science Publishing Group

Keywords

Evolution, Triplet Composon, Ortholog, G-protein Coupled Receptor, Odorant Receptor

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Miguel Angel Fuertes, Carlos Alonso. (2021). An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors. Ecology and Evolutionary Biology, 6(3), 53-77. https://doi.org/10.11648/j.eeb.20210603.11

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Miguel Angel Fuertes; Carlos Alonso. An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors. Ecol. Evol. Biol. 2021, 6(3), 53-77. doi: 10.11648/j.eeb.20210603.11

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Miguel Angel Fuertes, Carlos Alonso. An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors. Ecol Evol Biol. 2021;6(3):53-77. doi: 10.11648/j.eeb.20210603.11

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@article{10.11648/j.eeb.20210603.11,
  author = {Miguel Angel Fuertes and Carlos Alonso},
  title = {An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors},
  journal = {Ecology and Evolutionary Biology},
  volume = {6},
  number = {3},
  pages = {53-77},
  doi = {10.11648/j.eeb.20210603.11},
  url = {https://doi.org/10.11648/j.eeb.20210603.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.eeb.20210603.11},
  abstract = {Capturing conserved patterns in genes and proteins is important for inferring phenotype prediction and evolutionary analysis. The study is focused on the conserved patterns of the G protein-coupled receptors, an important superfamily of receptors. Olfactory receptors represent more than 2% of our genome and constitute the largest family of G protein-coupled receptors, a key class of drug targets. As no crystallographic structures are available, mechanistic studies rely on the use of molecular dynamic modelling combined with site-directed mutagenesis data. In this paper, we hypothesized that human-mouse orthologs coding for G protein-coupled receptors maintain, at speciation events, shared compositional structures independent, to some extent, of their percent identity as reveals a method based in the categorization of nucleotide triplets by their gross composition. The data support the consistency of the hypothesis, showing in ortholog G protein-coupled receptors the presence of emergent shared compositional structures preserved at speciation events. An extreme bias in synonymous codon usage is observed in both the conserved and non-conserved regions of many of these receptors that could be potentially relevant in codon optimization studies. The analysis of their compositional structures would help to design new evolutionary based strategies for rational mutations that would aid to understand the characteristics of individual G protein-coupled receptors, their subfamilies and the role in many physiological and pathological processes, supplying new possible drug targets.},
 year = {2021}
}

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TY  - JOUR
T1  - An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors
AU  - Miguel Angel Fuertes
AU  - Carlos Alonso
Y1  - 2021/07/13
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DO  - 10.11648/j.eeb.20210603.11
T2  - Ecology and Evolutionary Biology
JF  - Ecology and Evolutionary Biology
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AB  - Capturing conserved patterns in genes and proteins is important for inferring phenotype prediction and evolutionary analysis. The study is focused on the conserved patterns of the G protein-coupled receptors, an important superfamily of receptors. Olfactory receptors represent more than 2% of our genome and constitute the largest family of G protein-coupled receptors, a key class of drug targets. As no crystallographic structures are available, mechanistic studies rely on the use of molecular dynamic modelling combined with site-directed mutagenesis data. In this paper, we hypothesized that human-mouse orthologs coding for G protein-coupled receptors maintain, at speciation events, shared compositional structures independent, to some extent, of their percent identity as reveals a method based in the categorization of nucleotide triplets by their gross composition. The data support the consistency of the hypothesis, showing in ortholog G protein-coupled receptors the presence of emergent shared compositional structures preserved at speciation events. An extreme bias in synonymous codon usage is observed in both the conserved and non-conserved regions of many of these receptors that could be potentially relevant in codon optimization studies. The analysis of their compositional structures would help to design new evolutionary based strategies for rational mutations that would aid to understand the characteristics of individual G protein-coupled receptors, their subfamilies and the role in many physiological and pathological processes, supplying new possible drug targets.
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Author Information

Miguel Angel Fuertes

Department of Microbiology, Centre for Molecular Biology “Severo Ochoa”, Spanish National Research Council and Autonomous University, Madrid, Spain
Carlos Alonso

Department of Microbiology, Centre for Molecular Biology “Severo Ochoa”, Spanish National Research Council and Autonomous University, Madrid, Spain

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Miguel Angel Fuertes, Carlos Alonso. (2021). An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors. Ecology and Evolutionary Biology, 6(3), 53-77. https://doi.org/10.11648/j.eeb.20210603.11

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ACS Style

Miguel Angel Fuertes; Carlos Alonso. An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors. Ecol. Evol. Biol. 2021, 6(3), 53-77. doi: 10.11648/j.eeb.20210603.11

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AMA Style

Miguel Angel Fuertes, Carlos Alonso. An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors. Ecol Evol Biol. 2021;6(3):53-77. doi: 10.11648/j.eeb.20210603.11

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@article{10.11648/j.eeb.20210603.11,
  author = {Miguel Angel Fuertes and Carlos Alonso},
  title = {An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors},
  journal = {Ecology and Evolutionary Biology},
  volume = {6},
  number = {3},
  pages = {53-77},
  doi = {10.11648/j.eeb.20210603.11},
  url = {https://doi.org/10.11648/j.eeb.20210603.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.eeb.20210603.11},
  abstract = {Capturing conserved patterns in genes and proteins is important for inferring phenotype prediction and evolutionary analysis. The study is focused on the conserved patterns of the G protein-coupled receptors, an important superfamily of receptors. Olfactory receptors represent more than 2% of our genome and constitute the largest family of G protein-coupled receptors, a key class of drug targets. As no crystallographic structures are available, mechanistic studies rely on the use of molecular dynamic modelling combined with site-directed mutagenesis data. In this paper, we hypothesized that human-mouse orthologs coding for G protein-coupled receptors maintain, at speciation events, shared compositional structures independent, to some extent, of their percent identity as reveals a method based in the categorization of nucleotide triplets by their gross composition. The data support the consistency of the hypothesis, showing in ortholog G protein-coupled receptors the presence of emergent shared compositional structures preserved at speciation events. An extreme bias in synonymous codon usage is observed in both the conserved and non-conserved regions of many of these receptors that could be potentially relevant in codon optimization studies. The analysis of their compositional structures would help to design new evolutionary based strategies for rational mutations that would aid to understand the characteristics of individual G protein-coupled receptors, their subfamilies and the role in many physiological and pathological processes, supplying new possible drug targets.},
 year = {2021}
}

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TY  - JOUR
T1  - An Evolutionary Based Strategy for Predicting Rational Mutations in G Protein-Coupled Receptors
AU  - Miguel Angel Fuertes
AU  - Carlos Alonso
Y1  - 2021/07/13
PY  - 2021
N1  - https://doi.org/10.11648/j.eeb.20210603.11
DO  - 10.11648/j.eeb.20210603.11
T2  - Ecology and Evolutionary Biology
JF  - Ecology and Evolutionary Biology
JO  - Ecology and Evolutionary Biology
SP  - 53
EP  - 77
PB  - Science Publishing Group
SN  - 2575-3762
UR  - https://doi.org/10.11648/j.eeb.20210603.11
AB  - Capturing conserved patterns in genes and proteins is important for inferring phenotype prediction and evolutionary analysis. The study is focused on the conserved patterns of the G protein-coupled receptors, an important superfamily of receptors. Olfactory receptors represent more than 2% of our genome and constitute the largest family of G protein-coupled receptors, a key class of drug targets. As no crystallographic structures are available, mechanistic studies rely on the use of molecular dynamic modelling combined with site-directed mutagenesis data. In this paper, we hypothesized that human-mouse orthologs coding for G protein-coupled receptors maintain, at speciation events, shared compositional structures independent, to some extent, of their percent identity as reveals a method based in the categorization of nucleotide triplets by their gross composition. The data support the consistency of the hypothesis, showing in ortholog G protein-coupled receptors the presence of emergent shared compositional structures preserved at speciation events. An extreme bias in synonymous codon usage is observed in both the conserved and non-conserved regions of many of these receptors that could be potentially relevant in codon optimization studies. The analysis of their compositional structures would help to design new evolutionary based strategies for rational mutations that would aid to understand the characteristics of individual G protein-coupled receptors, their subfamilies and the role in many physiological and pathological processes, supplying new possible drug targets.
VL  - 6
IS  - 3
ER  -

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