Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression

Anthony V. Signore, Ying Zhong Yang, Quan Yu Yang, Ga Qin, Hideaki Moriyama, Ri Li Ge, Jay F. Storz, Claus Wilke

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the β-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked β-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the β-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.

Original languageEnglish (US)
Pages (from-to)2227-2237
Number of pages11
JournalMolecular biology and evolution
Volume36
Issue number10
DOIs
StatePublished - Oct 1 2019

Fingerprint

canid
Gene Conversion
gene conversion
Canidae
introgression
hemoglobin
mutation
Hemoglobins
wolves
Mutation
Globins
gene
protein engineering
Genes
Protein Engineering
Pseudogenes
protein
genes
pseudogenes
gene transfer

Keywords

  • Hemoglobin
  • High-altitude
  • Hypoxia
  • Introgression
  • Tibetan Wolf
  • Tibetan mastiff

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

Cite this

Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression. / Signore, Anthony V.; Yang, Ying Zhong; Yang, Quan Yu; Qin, Ga; Moriyama, Hideaki; Ge, Ri Li; Storz, Jay F.; Wilke, Claus.

In: Molecular biology and evolution, Vol. 36, No. 10, 01.10.2019, p. 2227-2237.

Research output: Contribution to journalArticle

Signore, Anthony V. ; Yang, Ying Zhong ; Yang, Quan Yu ; Qin, Ga ; Moriyama, Hideaki ; Ge, Ri Li ; Storz, Jay F. ; Wilke, Claus. / Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression. In: Molecular biology and evolution. 2019 ; Vol. 36, No. 10. pp. 2227-2237.
@article{698ff9715620462ab99d7c01ce557f8e,
title = "Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression",
abstract = "A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the β-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked β-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the β-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.",
keywords = "Hemoglobin, High-altitude, Hypoxia, Introgression, Tibetan Wolf, Tibetan mastiff",
author = "Signore, {Anthony V.} and Yang, {Ying Zhong} and Yang, {Quan Yu} and Ga Qin and Hideaki Moriyama and Ge, {Ri Li} and Storz, {Jay F.} and Claus Wilke",
year = "2019",
month = "10",
day = "1",
doi = "10.1093/molbev/msz097",
language = "English (US)",
volume = "36",
pages = "2227--2237",
journal = "Molecular Biology and Evolution",
issn = "0737-4038",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Adaptive Changes in Hemoglobin Function in High-Altitude Tibetan Canids Were Derived via Gene Conversion and Introgression

AU - Signore, Anthony V.

AU - Yang, Ying Zhong

AU - Yang, Quan Yu

AU - Qin, Ga

AU - Moriyama, Hideaki

AU - Ge, Ri Li

AU - Storz, Jay F.

AU - Wilke, Claus

PY - 2019/10/1

Y1 - 2019/10/1

N2 - A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the β-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked β-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the β-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.

AB - A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the β-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked β-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the β-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.

KW - Hemoglobin

KW - High-altitude

KW - Hypoxia

KW - Introgression

KW - Tibetan Wolf

KW - Tibetan mastiff

UR - http://www.scopus.com/inward/record.url?scp=85072627551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072627551&partnerID=8YFLogxK

U2 - 10.1093/molbev/msz097

DO - 10.1093/molbev/msz097

M3 - Article

C2 - 31362306

AN - SCOPUS:85072627551

VL - 36

SP - 2227

EP - 2237

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 10

ER -