@misc{oai:ir.soken.ac.jp:00001039,
 author = {弓削, 主哉 and ユゲ, カズヤ and YUGE, Kazuya},
 month = {2016-02-17, 2016-02-17},
 note = {The brains of most vertebrates are known to exhibit hermonal, chemical and <br />anatomical differences between males and females. However, molecular studies of sexual dimorphism in the vertebrate brains have not been well conducted. Moreover, the evolutionary process of sexual dimorphism in the vertebrate brains is almost unknewn. Thus, it is of particular importance to identify the sexually dimorphic genes in the brains and to study the evolutionary process of those genes. In this thesis, I first studied the sexually dimorphic genes expressed in the mouse brain and investigated the evelutionary emergence time of those genes in order to reveal evolutienary process of sexually dimorphic genes. <br />       <br /> In Chapter l, I described the outline of the present study, making special emphasis on the importance of evolutionary studies for sexually dimorphic genes in the vertebrate brains. <br /><br />        In Chapier 2, with the aim of elucidating the evolutionary process of sexual <br />dimorphism in the brain at the molecular level, I conducted genomic comparisons of a set of genes expressed in a sexually different manner in the mouse brain with all genes derived from 26 eukaryotic species whose complete genome sequences are available. In practice, first, I collected seventeen protein-coding genes whese levels of mRNA expression in the brain differed between male and female mice according to the currently available microarray data. I then designated these genes operationally as "sex-related genes in the mouse brain". Next, I estimated the time when these sex-related genes in the mouse brain emerged in the evolutionary process of eukaryotes by examining the presence or absence of the orthologues in all the eukaryotic species studied here.  As a result, I found that ten sex-related genes in the mouse brain emerged after the divergence of urochordates and mammals whereas the other seven <br />sex-related genes in the mouse brain emerged before the divergence of urochordates and mammals. In particular,  five out of the ten sex-related genes in the mouse brain emerged just before the appearance of bony fish which were known to have phenotypic sexual dimorphism in  the brain. Interestingly, three of these five sex-related genes that emerged during this period were classified into a functional category of the "protein binding". Moreover, all of these three genes were expected to have the functions that are related to cell-cell commnunications in the brain according to the gene expression patterns and/or functional information of these genes. <br />These findings suggest that the orthologues of the sex-related genes in the mouse brain having emerged just before the divergence of bony fish might have essential roles such as forming protein-protein interactions in the evolution of the sexual dimorphism in the brain. <br /><br />     In Chapter 3, l focused upon brain region-specificities of sexually dimorphic genes in the mouse and their　evelutionary processes, Vertebrate brains generally exhibit anatomical, biochemical and hormonal differences between males and females, and it is easily speculated that the genes manifesting sex-related features in a brain is different among brain regions because distinct brain regions have developed their specific functions at different evolutionary periods. However, little is known whether there are any differences in sex-related features among different brain regions of vertebrates from the evelutionary point of view. To investigate the differences of sexually dimorphic genes among brain regions of the mouse, I conducted comparative analysis of gene expression patterns between male and female mice. Microarray analyses of l8,538 transcripts of mice revealed 41, 44, 11 and 339 sexually dimorphic genes expressed in a preoptic area (POA), a hypothalamus (HY), an olfactory bulb (OB) and a pituitary (PIT), respectively. Furthermore, I found that proportions of brain-region specific dimorphic genes to all of the dimorphic genes in each of brain regions were 87.8% in the , POA, 86.4%  in the HY, 81.8%  in the OB and 98.5% in the PIT, respectively, when genes showing sexually dimorphic expression specifically in a brain region were operatianally defined as '"brain region-specific dimorphic genes". Thus, it suggests that the gene expression with sexually dimorphic characters exhibits a regional specificity in the mouse brain. Next, to explain the reason that the differences of gene expression patterns in sexual dimorphic genes among brain regions of the mouse appeared in the evolutionary process, orthologues of the sexually dimorphic genes of each brain region were collected and compared with their evolutienary emergence time. Consequently,I found that the evolutionary emergence time orthologues of these sexual dimorphic genes for each of the brain regions has varied with brain regions of the mouse. In fact, for the POA and the PIT, the brain region-specific dimorphic genes that emerged during early vertebrates in the evolutionary process were the most abundant among different evolutionary periods. On the other hand, the HY-specific dimorphic genes that emerged just befofe the divergence of nematodes in the evolutionary process were the most abundant among different evolutionary periods. These results sggest that the differences of gene expression patterns of sexually dimorphic genes among different brain regions might have evolutionarily developed their brain region-specificities. <br /><br />             In Chapter 4, I concluded that the orthologues of the sex-related genes in the mouse brain which emerged just before the divergence of bony fish might have essential roles in the evolution of the sexual dimorphism in the brain by forming protein-protein interactions. <br /><br />        Furthermore, l showed that the sexually dimorphic genes among 4 brain regions differ in their evolutionary process and these differences might be important for the development of the brain region-specificities. Finally, I emphasized that the present approach for utilizing a large set of gene expression data and gene gain and loss information is useful to understand the evolution of sexually dimorphic genes in the brain.<br />, application/pdf, 総研大甲第1099号},
 title = {Evolutionary studies of sex-related genes in the mouse brain},
 year = {}
}