Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Neuron-specific coding sequences are the most highly conserved in the mammalian brain

View ORCID ProfileLinhe Xu, View ORCID ProfileSuzana Herculano-Houzel
doi: https://doi.org/10.1101/2021.08.20.457147
Linhe Xu
aDepartment of Psychological Sciences, Vanderbilt University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Linhe Xu
Suzana Herculano-Houzel
aDepartment of Psychological Sciences, Vanderbilt University
bDepartment of Biological Sciences, Vanderbilt University
cVanderbilt Brain Institute, Vanderbilt University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Suzana Herculano-Houzel
  • For correspondence: suzana.herculano@vanderbilt.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

Neurons have become highly diverse in cell size, morphology, phenotype and function in mammalian evolution, whereas glial cells are much less varied in size and types across species. This difference in diversity suggests that neuron-specific protein-coding gene sequences have admitted more variation in evolution, that is, are less evolutionarily conserved than those expressed in glial cells. We calculated values of dN/dS from Ensembl98 for coding sequences expressed specifically in neurons, astrocytes, oligodendrocytes, microglia and endothelial cells in the brain across 92 mammalian species with reference to either mouse or human. Surprisingly, we find that protein-coding sequences that are specifically expressed in neurons are far less variable than those specific to other cell types in the brain. We next analyzed phastCons values for the same genes and found that neuron-specific promoter sequences are at least as conserved as other cell type-specific promoter sequences. Moreover, neuron-specific coding sequences are as highly conserved across mammalian species as ATPase coding sequences, the benchmark of evolutionary conservation, followed by heart and skeletal muscle-specific sequences. Neuronal diversity in mammalian evolution thus arises despite high levels of negative selection on neuron-specific protein-coding sequences. We propose that such strong evolutionary conservation is imposed by excitability, which continually exposes cells to the risk of excitotoxic death, and speculate that variability of neuronal cell sizes arises as a consequence of variability in levels of activity, possibly constrained by energy supply to the developing brain.

Significance Statement The majority of cells in the mammalian body, including glial cells in the brain, maintain a constant size across species from mice to elephants. The exception is neurons, whose size varies over 100-fold both within each brain and across species, often becoming larger in larger brains. What evolutionary mechanism allows neurons to be so exceptionally diverse in size? We show that neuron-specific genes are some of the most highly conserved in mammalian evolution, which implicates alternate causes of diversity in neuronal cell size beyond heritable genetics. We propose a novel direction of research into how neuronal cell size diversity might be a self-organized response to variations in levels of activity, which are an exclusive property of excitable cells like neurons.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Competing Interest Statement: The authors declare that they have no competing interests.

  • https://github.com/VeritatemAmo/neuron-glia-dNdS

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted August 21, 2021.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Neuron-specific coding sequences are the most highly conserved in the mammalian brain
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Neuron-specific coding sequences are the most highly conserved in the mammalian brain
Linhe Xu, Suzana Herculano-Houzel
bioRxiv 2021.08.20.457147; doi: https://doi.org/10.1101/2021.08.20.457147
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Neuron-specific coding sequences are the most highly conserved in the mammalian brain
Linhe Xu, Suzana Herculano-Houzel
bioRxiv 2021.08.20.457147; doi: https://doi.org/10.1101/2021.08.20.457147

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3688)
  • Biochemistry (7783)
  • Bioengineering (5673)
  • Bioinformatics (21267)
  • Biophysics (10574)
  • Cancer Biology (8170)
  • Cell Biology (11929)
  • Clinical Trials (138)
  • Developmental Biology (6757)
  • Ecology (10394)
  • Epidemiology (2065)
  • Evolutionary Biology (13853)
  • Genetics (9702)
  • Genomics (13063)
  • Immunology (8136)
  • Microbiology (19976)
  • Molecular Biology (7841)
  • Neuroscience (43032)
  • Paleontology (318)
  • Pathology (1278)
  • Pharmacology and Toxicology (2258)
  • Physiology (3350)
  • Plant Biology (7221)
  • Scientific Communication and Education (1311)
  • Synthetic Biology (2000)
  • Systems Biology (5533)
  • Zoology (1127)