TY - JOUR
T1 - Neofunctionalization of androgen receptor by Gain-of-Function mutations in teleost fish lineage
AU - Ogino, Yukiko
AU - Kuraku, Shigehiro
AU - Ishibashi, Hiroshi
AU - Miyakawa, Hitoshi
AU - Sumiya, Eri
AU - Miyagawa, Shinichi
AU - Matsubara, Hajime
AU - Yamada, Gen
AU - Baker, Michael E.
AU - Iguchi, Taisen
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Steroid hormone receptor family provides an example of evolution of diverse transcription factors through wholegenome duplication (WGD). However, little is known about how their functions have been evolved after the duplication. Teleosts present a good model to investigate an accurate evolutionary history of protein function after WGD, because a teleost-specific WGD (TSGD) resulted in a variety of duplicated genes in modern fishes. This study focused on the evolution of androgen receptor (AR) gene, as two distinct paralogs, ARa and ARb, have evolved in teleost lineage after TSGD. ARa showed a unique intracellular localization with a higher transactivation response than that of ARb. Using site-directed mutagenesis and computational prediction of protein-ligand interactions, we identified two key substitutions generating a new functionality of euteleost ARa. The substitution in the hinge region contributes to the unique intracellular localization of ARa. The substitution on helices 10/11 in the ligand-binding domain possibly modulates hydrogen bonds that stabilize the receptor-ligand complex leading to the higher transactivation response of ARa. These substitutions were conserved in Acanthomorpha (spiny-rayed fish) ARas, but not in an earlier branching lineage among teleosts, Japanese eel. Insertion of these substitutions into ARs from Japanese eel recapitulates the evolutionary novelty of euteleost ARa. These findings together indicate that the substitutions generating a new functionality of teleost ARa were fixed in teleost genome after the divergence of the Elopomorpha lineage. Our findings provide a molecular explanation for an adaptation process leading to generation of the hyperactive AR subtype after TSGD.
AB - Steroid hormone receptor family provides an example of evolution of diverse transcription factors through wholegenome duplication (WGD). However, little is known about how their functions have been evolved after the duplication. Teleosts present a good model to investigate an accurate evolutionary history of protein function after WGD, because a teleost-specific WGD (TSGD) resulted in a variety of duplicated genes in modern fishes. This study focused on the evolution of androgen receptor (AR) gene, as two distinct paralogs, ARa and ARb, have evolved in teleost lineage after TSGD. ARa showed a unique intracellular localization with a higher transactivation response than that of ARb. Using site-directed mutagenesis and computational prediction of protein-ligand interactions, we identified two key substitutions generating a new functionality of euteleost ARa. The substitution in the hinge region contributes to the unique intracellular localization of ARa. The substitution on helices 10/11 in the ligand-binding domain possibly modulates hydrogen bonds that stabilize the receptor-ligand complex leading to the higher transactivation response of ARa. These substitutions were conserved in Acanthomorpha (spiny-rayed fish) ARas, but not in an earlier branching lineage among teleosts, Japanese eel. Insertion of these substitutions into ARs from Japanese eel recapitulates the evolutionary novelty of euteleost ARa. These findings together indicate that the substitutions generating a new functionality of teleost ARa were fixed in teleost genome after the divergence of the Elopomorpha lineage. Our findings provide a molecular explanation for an adaptation process leading to generation of the hyperactive AR subtype after TSGD.
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U2 - 10.1093/molbev/msv218
DO - 10.1093/molbev/msv218
M3 - Article
C2 - 27413825
AN - SCOPUS:84964754673
VL - 33
SP - 228
EP - 244
JO - Molecular Biology and Evolution
JF - Molecular Biology and Evolution
SN - 0737-4038
IS - 1
ER -