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...
Published in: | eLife |
---|---|
Main Authors: | , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2018
|
Subjects: | |
Online Access: | https://doi.org/10.7554/eLife.38906 https://doaj.org/article/da60ee271fa04ee0abfc54b20e664b61 |
id |
ftdoajarticles:oai:doaj.org/article:da60ee271fa04ee0abfc54b20e664b61 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:da60ee271fa04ee0abfc54b20e664b61 2023-05-15T18:33:30+02:00 Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains David Jebb Michael Hiller 2018-10-01T00:00:00Z https://doi.org/10.7554/eLife.38906 https://doaj.org/article/da60ee271fa04ee0abfc54b20e664b61 EN eng eLife Sciences Publications Ltd https://elifesciences.org/articles/38906 https://doaj.org/toc/2050-084X doi:10.7554/eLife.38906 2050-084X e38906 https://doaj.org/article/da60ee271fa04ee0abfc54b20e664b61 eLife, Vol 7 (2018) mammals cetaceans fruit bats elephants Medicine R Science Q Biology (General) QH301-705.5 article 2018 ftdoajarticles https://doi.org/10.7554/eLife.38906 2022-12-30T20:56:29Z 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 Directory of Open Access Journals: DOAJ Articles eLife 7 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
mammals cetaceans fruit bats elephants Medicine R Science Q Biology (General) QH301-705.5 |
spellingShingle |
mammals cetaceans fruit bats elephants Medicine R Science Q Biology (General) QH301-705.5 David Jebb Michael Hiller Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains |
topic_facet |
mammals cetaceans fruit bats elephants Medicine R Science Q Biology (General) QH301-705.5 |
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 |
David Jebb Michael Hiller |
author_facet |
David Jebb Michael Hiller |
author_sort |
David Jebb |
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 |
https://doi.org/10.7554/eLife.38906 https://doaj.org/article/da60ee271fa04ee0abfc54b20e664b61 |
genre |
toothed whales |
genre_facet |
toothed whales |
op_source |
eLife, Vol 7 (2018) |
op_relation |
https://elifesciences.org/articles/38906 https://doaj.org/toc/2050-084X doi:10.7554/eLife.38906 2050-084X e38906 https://doaj.org/article/da60ee271fa04ee0abfc54b20e664b61 |
op_doi |
https://doi.org/10.7554/eLife.38906 |
container_title |
eLife |
container_volume |
7 |
_version_ |
1766218122059055104 |