Inference of epistatic effects in a key mitochondrial protein

Erik D. Nelson, Nick V. Grishin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We use Potts model inference to predict pair epistatic effects in a key mitochondrial protein - cytochrome c oxidase subunit 2 - for ray-finned fishes. We examine the effect of phylogenetic correlations on our predictions using a simple exact fitness model, and we find that, although epistatic effects are underpredicted, they maintain a roughly linear relationship to their true (model) values. After accounting for this correction, epistatic effects in the protein are still relatively weak, leading to fitness valleys of depth 2Ns≃-5 in compensatory double mutants. Interestingly, positive epistasis is more pronounced than negative epistasis, and the strongest positive effects capture nearly all sites subject to positive selection in fishes, similar to virus proteins evolving under selection pressure in the context of drug therapy.

Original languageEnglish (US)
Article number062404
JournalPhysical Review E
Volume97
Issue number6
DOIs
StatePublished - Jun 11 2018

Fingerprint

inference
proteins
Protein
fitness
fishes
Epistasis
Fish
capture effect
Fitness
oxidase
cytochromes
viruses
chemotherapy
valleys
Potts Model
Phylogenetics
rays
Mutant
Virus
Therapy

ASJC Scopus subject areas

  • Statistical and Nonlinear Physics
  • Statistics and Probability
  • Condensed Matter Physics

Cite this

Inference of epistatic effects in a key mitochondrial protein. / Nelson, Erik D.; Grishin, Nick V.

In: Physical Review E, Vol. 97, No. 6, 062404, 11.06.2018.

Research output: Contribution to journalArticle

@article{a939eac2232344048879a62a1a879234,
title = "Inference of epistatic effects in a key mitochondrial protein",
abstract = "We use Potts model inference to predict pair epistatic effects in a key mitochondrial protein - cytochrome c oxidase subunit 2 - for ray-finned fishes. We examine the effect of phylogenetic correlations on our predictions using a simple exact fitness model, and we find that, although epistatic effects are underpredicted, they maintain a roughly linear relationship to their true (model) values. After accounting for this correction, epistatic effects in the protein are still relatively weak, leading to fitness valleys of depth 2Ns≃-5 in compensatory double mutants. Interestingly, positive epistasis is more pronounced than negative epistasis, and the strongest positive effects capture nearly all sites subject to positive selection in fishes, similar to virus proteins evolving under selection pressure in the context of drug therapy.",
author = "Nelson, {Erik D.} and Grishin, {Nick V.}",
year = "2018",
month = "6",
day = "11",
doi = "10.1103/PhysRevE.97.062404",
language = "English (US)",
volume = "97",
journal = "Physical review. E",
issn = "2470-0045",
publisher = "American Physical Society",
number = "6",

}

TY - JOUR

T1 - Inference of epistatic effects in a key mitochondrial protein

AU - Nelson, Erik D.

AU - Grishin, Nick V.

PY - 2018/6/11

Y1 - 2018/6/11

N2 - We use Potts model inference to predict pair epistatic effects in a key mitochondrial protein - cytochrome c oxidase subunit 2 - for ray-finned fishes. We examine the effect of phylogenetic correlations on our predictions using a simple exact fitness model, and we find that, although epistatic effects are underpredicted, they maintain a roughly linear relationship to their true (model) values. After accounting for this correction, epistatic effects in the protein are still relatively weak, leading to fitness valleys of depth 2Ns≃-5 in compensatory double mutants. Interestingly, positive epistasis is more pronounced than negative epistasis, and the strongest positive effects capture nearly all sites subject to positive selection in fishes, similar to virus proteins evolving under selection pressure in the context of drug therapy.

AB - We use Potts model inference to predict pair epistatic effects in a key mitochondrial protein - cytochrome c oxidase subunit 2 - for ray-finned fishes. We examine the effect of phylogenetic correlations on our predictions using a simple exact fitness model, and we find that, although epistatic effects are underpredicted, they maintain a roughly linear relationship to their true (model) values. After accounting for this correction, epistatic effects in the protein are still relatively weak, leading to fitness valleys of depth 2Ns≃-5 in compensatory double mutants. Interestingly, positive epistasis is more pronounced than negative epistasis, and the strongest positive effects capture nearly all sites subject to positive selection in fishes, similar to virus proteins evolving under selection pressure in the context of drug therapy.

UR - http://www.scopus.com/inward/record.url?scp=85048510829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048510829&partnerID=8YFLogxK

U2 - 10.1103/PhysRevE.97.062404

DO - 10.1103/PhysRevE.97.062404

M3 - Article

C2 - 30011480

AN - SCOPUS:85048510829

VL - 97

JO - Physical review. E

JF - Physical review. E

SN - 2470-0045

IS - 6

M1 - 062404

ER -