Stepwise Evolution of a Buried Inhibitor Peptide over 45 My

Achala S Jayasena, Mark F Fisher, Jose L Panero, David Secco, Kalia Bernath-Levin, Oliver Berkowitz, Nicolas L Taylor, Edward E Schilling, James Whelan, Josh Mylne

Research output: Contribution to journalArticle

8 Citations (Scopus)
138 Downloads (Pure)

Abstract

The de novo evolution of genes and the novel proteins they encode has stimulated much interest in the contribution such innovations make to the diversity of life. Most research on this de novo evolution focuses on transcripts, so studies on the biochemical steps that can enable completely new proteins to evolve and the time required to do so have been lacking. Sunflower Preproalbumin with SFTI-1 (PawS1) is an unusual albumin precursor because in addition to producing albumin it also yields a potent, bicyclic protease-inhibitor called SunFlower Trypsin Inhibitor-1 (SFTI-1). Here, we show how this inhibitor peptide evolved stepwise over tens of millions of years. To trace the origin of the inhibitor peptide SFTI-1, we assembled seed transcriptomes for 110 sunflower relatives whose evolution could be resolved by a chronogram, which allowed dates to be estimated for the various stages of molecular evolution. A genetic insertion event in an albumin precursor gene ∼45 Ma introduced two additional cleavage sites for protein maturation and conferred duality upon PawS1-Like genes such that they also encode a small buried macrocycle. Expansion of this region, including two Cys residues, enlarged the peptide ∼34 Ma and made the buried peptides bicyclic. Functional specialization into a protease inhibitor occurred ∼23 Ma. These findings document the evolution of a novel peptide inside a benign region of a pre-existing protein. We illustrate how a novel peptide can evolve without de novo gene evolution and, critically, without affecting the function of what becomes the protein host.

Original languageEnglish
Pages (from-to)1505-1516
Number of pages12
JournalMolecular Biology and Evolution
Volume34
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Fingerprint

peptide
inhibitor
Helianthus annuus
peptides
Peptides
trypsin inhibitors
albumins
protein
Albumins
Helianthus
proteinase inhibitors
Proteins
Protease Inhibitors
gene
proteins
genes
Genes
Molecular Evolution
Transcriptome
transcriptome

Cite this

Jayasena, Achala S ; Fisher, Mark F ; Panero, Jose L ; Secco, David ; Bernath-Levin, Kalia ; Berkowitz, Oliver ; Taylor, Nicolas L ; Schilling, Edward E ; Whelan, James ; Mylne, Josh. / Stepwise Evolution of a Buried Inhibitor Peptide over 45 My. In: Molecular Biology and Evolution. 2017 ; Vol. 34, No. 6. pp. 1505-1516.
@article{a5ed97f28ac343e59cbf5d2884651e6a,
title = "Stepwise Evolution of a Buried Inhibitor Peptide over 45 My",
abstract = "The de novo evolution of genes and the novel proteins they encode has stimulated much interest in the contribution such innovations make to the diversity of life. Most research on this de novo evolution focuses on transcripts, so studies on the biochemical steps that can enable completely new proteins to evolve and the time required to do so have been lacking. Sunflower Preproalbumin with SFTI-1 (PawS1) is an unusual albumin precursor because in addition to producing albumin it also yields a potent, bicyclic protease-inhibitor called SunFlower Trypsin Inhibitor-1 (SFTI-1). Here, we show how this inhibitor peptide evolved stepwise over tens of millions of years. To trace the origin of the inhibitor peptide SFTI-1, we assembled seed transcriptomes for 110 sunflower relatives whose evolution could be resolved by a chronogram, which allowed dates to be estimated for the various stages of molecular evolution. A genetic insertion event in an albumin precursor gene ∼45 Ma introduced two additional cleavage sites for protein maturation and conferred duality upon PawS1-Like genes such that they also encode a small buried macrocycle. Expansion of this region, including two Cys residues, enlarged the peptide ∼34 Ma and made the buried peptides bicyclic. Functional specialization into a protease inhibitor occurred ∼23 Ma. These findings document the evolution of a novel peptide inside a benign region of a pre-existing protein. We illustrate how a novel peptide can evolve without de novo gene evolution and, critically, without affecting the function of what becomes the protein host.",
keywords = "Journal Article",
author = "Jayasena, {Achala S} and Fisher, {Mark F} and Panero, {Jose L} and David Secco and Kalia Bernath-Levin and Oliver Berkowitz and Taylor, {Nicolas L} and Schilling, {Edward E} and James Whelan and Josh Mylne",
note = "{\circledC} The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2017",
month = "6",
day = "1",
doi = "10.1093/molbev/msx104",
language = "English",
volume = "34",
pages = "1505--1516",
journal = "Molecular Biology and Evolution",
issn = "0737-4038",
publisher = "Oxford University Press",
number = "6",

}

Stepwise Evolution of a Buried Inhibitor Peptide over 45 My. / Jayasena, Achala S; Fisher, Mark F; Panero, Jose L; Secco, David; Bernath-Levin, Kalia; Berkowitz, Oliver; Taylor, Nicolas L; Schilling, Edward E; Whelan, James; Mylne, Josh.

In: Molecular Biology and Evolution, Vol. 34, No. 6, 01.06.2017, p. 1505-1516.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Stepwise Evolution of a Buried Inhibitor Peptide over 45 My

AU - Jayasena, Achala S

AU - Fisher, Mark F

AU - Panero, Jose L

AU - Secco, David

AU - Bernath-Levin, Kalia

AU - Berkowitz, Oliver

AU - Taylor, Nicolas L

AU - Schilling, Edward E

AU - Whelan, James

AU - Mylne, Josh

N1 - © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - The de novo evolution of genes and the novel proteins they encode has stimulated much interest in the contribution such innovations make to the diversity of life. Most research on this de novo evolution focuses on transcripts, so studies on the biochemical steps that can enable completely new proteins to evolve and the time required to do so have been lacking. Sunflower Preproalbumin with SFTI-1 (PawS1) is an unusual albumin precursor because in addition to producing albumin it also yields a potent, bicyclic protease-inhibitor called SunFlower Trypsin Inhibitor-1 (SFTI-1). Here, we show how this inhibitor peptide evolved stepwise over tens of millions of years. To trace the origin of the inhibitor peptide SFTI-1, we assembled seed transcriptomes for 110 sunflower relatives whose evolution could be resolved by a chronogram, which allowed dates to be estimated for the various stages of molecular evolution. A genetic insertion event in an albumin precursor gene ∼45 Ma introduced two additional cleavage sites for protein maturation and conferred duality upon PawS1-Like genes such that they also encode a small buried macrocycle. Expansion of this region, including two Cys residues, enlarged the peptide ∼34 Ma and made the buried peptides bicyclic. Functional specialization into a protease inhibitor occurred ∼23 Ma. These findings document the evolution of a novel peptide inside a benign region of a pre-existing protein. We illustrate how a novel peptide can evolve without de novo gene evolution and, critically, without affecting the function of what becomes the protein host.

AB - The de novo evolution of genes and the novel proteins they encode has stimulated much interest in the contribution such innovations make to the diversity of life. Most research on this de novo evolution focuses on transcripts, so studies on the biochemical steps that can enable completely new proteins to evolve and the time required to do so have been lacking. Sunflower Preproalbumin with SFTI-1 (PawS1) is an unusual albumin precursor because in addition to producing albumin it also yields a potent, bicyclic protease-inhibitor called SunFlower Trypsin Inhibitor-1 (SFTI-1). Here, we show how this inhibitor peptide evolved stepwise over tens of millions of years. To trace the origin of the inhibitor peptide SFTI-1, we assembled seed transcriptomes for 110 sunflower relatives whose evolution could be resolved by a chronogram, which allowed dates to be estimated for the various stages of molecular evolution. A genetic insertion event in an albumin precursor gene ∼45 Ma introduced two additional cleavage sites for protein maturation and conferred duality upon PawS1-Like genes such that they also encode a small buried macrocycle. Expansion of this region, including two Cys residues, enlarged the peptide ∼34 Ma and made the buried peptides bicyclic. Functional specialization into a protease inhibitor occurred ∼23 Ma. These findings document the evolution of a novel peptide inside a benign region of a pre-existing protein. We illustrate how a novel peptide can evolve without de novo gene evolution and, critically, without affecting the function of what becomes the protein host.

KW - Journal Article

U2 - 10.1093/molbev/msx104

DO - 10.1093/molbev/msx104

M3 - Article

VL - 34

SP - 1505

EP - 1516

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 6

ER -