| 1. |
Yukiko Ogino, Satoshi Ansai, Hirotaka Sakamoto, Eiji Watanabe, Kiyoshi Naruse and Taisen Iguchi, Molecular basis of androgen dependent sex characteristics development and evolution with teleost fishes as model species, 第42回日本分子生物学会年会 , 2019.12, Teleost fishes offer a clue to understanding the evolution of secondary sex characteristics, because they acquired two different subtypes of the AR gene, ARa and ARb, in the teleost-specific whole genome duplication, which might have led to their diversified masculine sex characteristics for appendage development and also sexual behavior. To address the significance of the AR gene duplication, we analyzed the morphological and behavioral phenotypes of medaka mutants for ARa and ARb genes. ARb have predominant function for external masculine phenotypes, and AR might contribute to the development of traits for male-male competition. Both ARs showed the functional redundancy in the courtship behavior, whereas double mutant male of ARa and ARb is infertile due to the loss of courtship behavior, indicating that AR gene duplication can ensure each AR to acquire the attractive function for reproduction, while stabilizing the capability of reproduction by functional redundancy. We also generated the knock-in medaka lines expressing each AR as a fusion protein with FLAG, which allows the production of mClover3 as a separated protein to visualize the spatio-temporal expression and intracellular localization of each AR in vivo. Consistent with the mutant phenotypes, ARb is predominantly expressed in the condensed mesenchyme enriched for expression of androgen effector genes in the anal fin, while ARa is highly expressed in the brain of superior male, indicating the relationship between the expression divergence of each AR and morphological diversification. Our findings would provide a historical explanation for the retention of the duplicated AR copies in the teleost genome.. |
| 2. |
Yukiko Ogino, Hirotaka Sakamoto, Eiji Watanabe, Satoshi Ansai, Kiyoshi Naruse and Taisen Iguchi, Functional analysis of two distinct paralogs of androgen receptor for the sex characteristics development in medaka, 52th Annual Meeting of the Japanese Society of Developmental Biologists, 2019.05. |
| 3. |
Yukiko Ogino, Hirotaka Sakamoto, Eiji Watanabe and Taisen Iguchi, Diversification of androgen receptor function underlies secondary sex characteristics development of teleost fishes. , 4th Strategic Meeting for Medaka Research,3rd Regional Fish Meeting, 2018.04, Gene duplication is a dominant driving force of evolution. Steroid hormone receptor gene family is thought to have arisen from gene duplication. However, the molecular events which produce new protein functions after the genome duplication have not been fully understood. Teleost fishes present a good model to investigate an accurate evolutionary history of protein function after whole genome duplication, because the teleost-specific whole genome duplication (TSGD) 350 million years ago resulted in a variety of duplicated genes that exist in modern fishes. We focused on the androgen receptor (AR) gene, since two different subtype genes, AR and AR, were generated in the TSGD. AR has retained the ancestral function, whereas the AR evolved as a hyperactive form of AR in the teleost lineage. Results of our combined functional and 3 dimensional analyses of medaka (Oryzias latipes) ARs identified the substitutions that led to changes in protein structure and function between medaka AR and AR. One substitution located within the helices 10/11 of ligand binding domain is sufficient for generating higher transactivation of AR. This amino acid change affects the stability of ligand binding by modifying the hydrogen bonds between ligand and AR.
To further address the functional differences between AR and AR in vivo, we isolated the nonsense mutants of AR and AR from the medaka tilling library. AR have predominant function for external masculine phenotypes, and AR might participate the development of traits for male-male competition. Our findings would provide an historical explanation for the retention of the duplicated AR copies in euteleost genome.. |
| 4. |
荻野 由紀子, 井口泰泉, Evolutionary diversification of androgen dependent sex characteristics development in teleost fishes., The 22nd International Congress of Zoology, 2016.11. |
| 5. |
荻野 由紀子, Functional and evolutionary analyses of androgen receptor gene in teleost fishes: Molecular basis of diversified sex characteristics development, 小型魚類研究会, 2016.08. |
