Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains
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, comp...
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ftpubman:oai:pure.mpg.de:item_3008671 2023-08-20T04:10:09+02:00 Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains Jebb, D. Hiller, M. 2018-10-16 http://hdl.handle.net/21.11116/0000-0002-7BC9-2 unknown info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.38906 http://hdl.handle.net/21.11116/0000-0002-7BC9-2 eLife Living matter info:eu-repo/semantics/article 2018 ftpubman https://doi.org/10.7554/eLife.38906 2023-08-01T23:44:50Z 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. Article in Journal/Newspaper toothed whales Max Planck Society: MPG.PuRe eLife 7 |
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Living matter Jebb, D. Hiller, M. Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
topic_facet |
Living matter |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Jebb, D. Hiller, M. |
author_facet |
Jebb, D. Hiller, M. |
author_sort |
Jebb, D. |
title |
Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
title_short |
Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
title_full |
Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
title_fullStr |
Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
title_full_unstemmed |
Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
title_sort |
recurrent loss of hmgcs2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
publishDate |
2018 |
url |
http://hdl.handle.net/21.11116/0000-0002-7BC9-2 |
genre |
toothed whales |
genre_facet |
toothed whales |
op_source |
eLife |
op_relation |
info:eu-repo/semantics/altIdentifier/doi/10.7554/eLife.38906 http://hdl.handle.net/21.11116/0000-0002-7BC9-2 |
op_doi |
https://doi.org/10.7554/eLife.38906 |
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eLife |
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7 |
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1774724158976950272 |