Gene Loss

Publication Details

Identifier: JB_ZQQIXM

Curator: Raul Valente

Title:

Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains.

Abstract:

Apart from glucose, fatty acid-derived ketone bodies provide metabolic energy for the brain during fasting and neonatal development. We investigated the evolution of HMGCS2, the key enzyme required for ketone body biosynthesis (ketogenesis). Unexpectedly, we found that three mammalian lineages, comprising cetaceans (dolphins and whales), elephants and mastodons, and Old World fruit bats have lost this gene. Remarkably, many of these species have exceptionally large brains and signs of intelligent behavior. While fruit bats are sensitive to starvation, cetaceans and elephants can still withstand periods of fasting. This suggests that alternative strategies to fuel large brains during fasting evolved repeatedly and reveals flexibility in mammalian energy metabolism. Furthermore, we show that HMGCS2 loss preceded brain size expansion in toothed whales and elephants. Thus, while ketogenesis was likely important for brain size expansion in modern humans, ketogenesis is not a universal precondition for the evolution of large mammalian brains.

Last update:

09-10-2024

Associated Glosses (23 results)

GlossID	Species	Symbol	Gene Loss Mechanism	Loss Type	Lineage Specific	Citation
GL_48AXH7	Pteropus vampyrus	BDH1	LOF (frameshift, premature stop, ss)	Full	Pteropodidae	10.7554/eLife.38906
GL_5PFKJS	Physeter catodon	BDH1	LOF (frameshift, premature stop, ss)	Full	Cetacea	10.7554/eLife.38906
GL_8LPBLZ	Pteropus alecto	BDH1	LOF (frameshift, premature stop, ss)	Full	Pteropodidae	10.7554/eLife.38906
GL_9NBNYR	Pteropus vampyrus	HMGCS2	Exon(s) deletion	Full	Pteropodidae	10.7554/eLife.38906
GL_EAHMDR	Elephas maximus	HMGCS2	Exon(s) deletion	Full	Proboscidea	10.7554/eLife.38906
GL_GURUHT	Tursiops truncatus	BDH1	LOF (frameshift, premature stop, ss)	Full	Cetacea	10.7554/eLife.38906
GL_HBSV6K	Rousettus aegyptiacus	HMGCS2	Gene deletion	Full	Pteropodidae	10.7554/eLife.38906
GL_JC1NDT	Orcinus orca	BDH1	LOF (frameshift, premature stop, ss)	Full	Cetacea	10.7554/eLife.38906
GL_JRE36C	Loxodonta africana	HMGCS2	Exon(s) deletion	Full	Proboscidea	10.7554/eLife.38906
GL_JZGB6F	Loxodonta africana	REG4	Gene deletion	Full	Proboscidea	10.7554/eLife.38906