Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify mechanisms for seasonal energy balance.

Abstract

Synthesis of triiodothyronine (T₃) in the hypothalamus induces marked seasonal neuromorphology changes across taxa. How species-specific responses to T₃ signaling in the CNS drive annual changes in body weight and energy balance remains uncharacterized. These experiments sequenced and annotated the Siberian hamster (<i>Phodopus sungorus</i>) genome, a model organism for seasonal physiology research, to facilitate the dissection of T₃-dependent molecular mechanisms that govern predictable, robust, and long-term changes in body weight. Examination of the <i>Phodopus</i> genome, in combination with transcriptome sequencing of the hamster diencephalon under winter and summer conditions, and in vivo-targeted expression analyses confirmed that proopiomelanocortin (<i>pomc</i>) is a primary genomic target for the long-term T₃-dependent regulation of body weight. Further in silico analyses of <i>pomc</i> promoter sequences revealed that thyroid hormone receptor 1β-binding motif insertions have evolved in several genera of the Cricetidae family of rodents. Finally, experimental manipulation of food availability confirmed that hypothalamic <i>pomc</i> mRNA expression is dependent on longer-term photoperiod cues and is unresponsive to acute, short-term food availability. These observations suggest that species-specific responses to hypothalamic T₃, driven in part by the receptor-binding motif insertions in some cricetid genomes, contribute critically to the long-term regulation of energy balance and the underlying physiological and behavioral adaptations associated with the seasonal organization of behavior.