付記する学位プログラム名: 霊長類学・ワイルドライフサイエンス・リーディング大学院 / 京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20964号 / 理博第4416号 / 新制||理||1634(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)准教授 Michael Alan Huffman, 准教授 足立 幾磨, 教授 友永 雅己 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

Due to an extreme asymmetry in parental investment, raising the potential for sexual conflict, orangutans provide unique insights into the role of sexual conflict in male and female reproductive strategies. Sexual selection acts on reproductive strategies, selecting for strategies that increase an individual's reproductive success. Sexual conflict results when the reproductive strategies of one sex impose costs on the other. Three forms of sexual selection have been documented in orangutans—male-male competition, female choice, and sexual coercion. This dissertation asks (1) how males employ reproductive strategies to increase their likelihood of reproductive success in the face of multi-male mating by females and (2) how females employ reproductive strategies to enact female choice and increase infant survival in the face of male-male competition and sexual coercion. I investigate these two questions using genetic paternity, long-term association data, and a year of behavioral data from orangutans (Pongo pygmaeus wurmbii) in Gunung Palung National Park, West Kalimantan, Indonesia. Brown-modified Hinde Indices, initiation and termination of associations, and following data reveal that female participation is necessary to sustain longer male-female associations and females use facultative associations to employ mate choice. Genetic paternity determination found low reproductive skew, with flanged males siring more offspring than unflanged males. Investigation of female infanticide avoidance strategies showed that females with dependent offspring under age six associate with males less often than other categories of females do, and mothers decrease the distance with their offspring during associations with males. These results highlight the importance of both female choice and male-male competition in reproductive outcomes, and illustrate how facultative associations play a key role in the reproductive strategies of both male and female orangutans. Both sexes’ strategies are studied, demonstrating the dynamic co-evolution of strategies and counterstrategies. I also consider the implications of these findings for the evolution of male bimaturism. Examining orangutan mating and reproductive behaviors deepens our understanding of how sexual conflict and sexual selection have shaped their unusual mating system and broadens our understanding of sexual conflict in reproductive strategies in a species with an extreme disparity between maternal and paternal investment. / 2025-08-31T00:00:00Z

Adipositas ist eine polymorphe chronische Erkrankung mit epidemischer Prävalenz. Im katabolen Leptin-Melanocortin-Signalweg ist das Proopiomelanocortin Gen (POMC) ein zentrales Element, das bei Dysfunktion massive Adipositas bewirken kann. Auch eine kürzlich identifizierte intragenische Methylierungsvariante des POMC wurde mit Adipositas assoziiert und deutet somit auf eine mögliche epigenetische Modulation des Gewichtsphänotyps hin. Zur Aufklärung der Relevanz, Stabilität und Entwicklung dieser epigenetischen Modifikation wurden die Funktionalität, Ontogenese und Phylogenese der POMC DNA-Methylierung untersucht. In vitro Analysen zeigten DNA-Methylierungsabhängige Promoteraktivität beider CpG-Inseln (CGIs) des POMC. Diese hier erstmals beschriebene Transkriptionsaktivität der intragenischen CGI weist auf einen alternativen Promoter des POMC hin. Hinsichtlich der Ontogenese konnten in Mensch und Maus postnatal stabile DNA-Methylierungsmuster mit interindividueller Konservierung für beide CGIs des POMC identifiziert werden. Zusätzlich erwiesen sich Gewebeunabhängigkeit der DNA-Methylierungsmuster und ihre pränatale Ausbildung zwischen dem Blastocystenstadium und der frühen Organogenese in der Maus. Die POMC DNA-Methylierungsmuster upstream des Exon3 unterscheiden sich in Mensch und Maus. Der mögliche Einfluss von primatenspezifischen Alu-Elementen im Intron2 des POMC hierauf wurde in verschiedenen Primatenfamilien analysiert. Die Ergebnisse zeigen eine bedingte Assoziation der Alu-Elemente mit der DNA-Methylierung in der entsprechenden Region, lassen jedoch auch weitere Einflussfaktoren vermuten. Insgesamt zeigt diese Arbeit, dass die POMC DNA-Methylierung artspezifisch konserviert ist und in der frühen Embryogenese, vermutlich Alu-abhängig, ausgebildet wird. Dabei könnten stochastische Variationen der DNA-Methylierung die POMC-Aktivität beeinflussen und somit das Risiko für Adipositas erhöhen. / Obesity is a polymorphic chronic disease with epidemic prevalence. Within the catabolic leptin-melanocortin signaling pathway pre-proopiomelanocortin (POMC) is a pivotal element. Dysfunction of POMC, e.g. due to mutations, can cause severe obesity. Moreover, a recently identified intragenic methylation variant of POMC was found to be associated with obesity. Therefore, this indicates potential epigenetic modulation of the weight phenotype. To gain further insight into the relevance, stability, and origin of this epigenetic modification, the functionality, ontogenesis, and phylogenesis of the POMC DNA methylation patterns were analyzed. In vitro analyses revealed DNA methylation-dependent promoter activity of both CpG islands (CGIs) of POMC. Thereby, the intragenic CGI was identified as a potential alternative promoter of POMC, which has not been described before. Regarding the ontogenesis, postnatally stable POMC DNA methylation patterns with interindividual conservation were detected for both CGIs in humans and mice. In addition, it was observed that the POMC DNA methylation patterns are non-tissue-specific, stable upon long time administration of a high fat diet, and develop prenatally between the blastocystal stage and the early organogenesis. The POMC DNA methylation pattern upstream of exon3 differs in humans and mice. A possible influence of primate-specific Alu elements within the intron2 region of POMC was analyzed in various primate families. Results evince a partial association of the Alu elements with the DNA methylation pattern in this particular region, but also suggest an influence of additional factors. Overall, this work demonstrates that DNA methylation of the POMC locus is species-specific highly conserved, and that it is established during early embryogenesis, possibly Alu-triggered. In the course of this, stochastic variances of the POMC DNA methylation might influence the POMC activity and consequently alter the risk to develop obesity.

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