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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crelifesciences:10.7554/elife.38906 2024-05-19T07:49:29+00:00 Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains Jebb, David Hiller, Michael Max-Planck-Gesellschaft Deutsche Forschungsgemeinschaft 2018 http://dx.doi.org/10.7554/elife.38906 https://cdn.elifesciences.org/articles/38906/elife-38906-v1.pdf https://cdn.elifesciences.org/articles/38906/elife-38906-v1.xml https://elifesciences.org/articles/38906 en eng eLife Sciences Publications, Ltd http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ eLife volume 7 ISSN 2050-084X journal-article 2018 crelifesciences https://doi.org/10.7554/elife.38906 2024-05-01T07:20:31Z 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 eLife eLife 7 |
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eLife |
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crelifesciences |
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English |
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. |
author2 |
Max-Planck-Gesellschaft Deutsche Forschungsgemeinschaft |
format |
Article in Journal/Newspaper |
author |
Jebb, David Hiller, Michael |
spellingShingle |
Jebb, David Hiller, Michael Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
author_facet |
Jebb, David Hiller, Michael |
author_sort |
Jebb, David |
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 |
publisher |
eLife Sciences Publications, Ltd |
publishDate |
2018 |
url |
http://dx.doi.org/10.7554/elife.38906 https://cdn.elifesciences.org/articles/38906/elife-38906-v1.pdf https://cdn.elifesciences.org/articles/38906/elife-38906-v1.xml https://elifesciences.org/articles/38906 |
genre |
toothed whales |
genre_facet |
toothed whales |
op_source |
eLife volume 7 ISSN 2050-084X |
op_rights |
http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.7554/elife.38906 |
container_title |
eLife |
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7 |
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1799467978421436416 |