Whole-brain comparison of rodent and human brains using spatial transcriptomics
- University of Toronto, Canada
- Mouse Imaging Centre, Canada
- Hospital for Sick Children, Canada
- National Institute of Mental Health, United States
- Radboud University Nijmegen, Netherlands
- University of Oxford, United Kingdom
Abstract
The ever-increasing use of mouse models in preclinical neuroscience research calls for an improvement in the methods used to translate findings between mouse and human brains. Previously we showed that the brains of primates can be compared in a direct quantitative manner using a common reference space built from white matter tractography data (Rogier B. Mars et al., 2018b). Here we extend the common space approach to evaluate the similarity of mouse and human brain regions using openly accessible brain-wide transcriptomic data sets. We show that mouse-human homologous genes capture broad patterns of neuroanatomical organization, but that the resolution of cross-species correspondences can be improved using a novel supervised machine learning approach. Using this method, we demonstrate that sensorimotor subdivisions of the neocortex exhibit greater similarity between species, compared with supramodal subdivisions, and that mouse isocortical regions separate into sensorimotor and supramodal clusters based on their similarity to human cortical regions. We also find that mouse and human striatal regions are strongly conserved, with the mouse caudoputamen exhibiting an equal degree of similarity to both the human caudate and putamen.
Data availability
The Allen Mouse Brain Atlas and Allen Human Brain Atlas data sets are openly accessible and can be downloaded from the Allen Institute's API (http://api.brain-map.org). All of the code and additional data needed to generate this analysis, including figures and manuscript, is accessible at https://github.com/abeaucha/MouseHumanTranscriptomicSimilarity/
Article and author information
Author details
Funding
Canadian Institutes of Health Research (Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships (GSD-165737))
- Antoine Beauchamp
Wellcome Trust (203139/Z/16/Z)
- Rogier B Mars
- Jason P Lerch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Alex Fornito, Monash University, Australia
Version history
- Preprint posted: March 18, 2022 (view preprint)
- Received: April 12, 2022
- Accepted: November 4, 2022
- Accepted Manuscript published: November 7, 2022 (version 1)
- Version of Record published: November 29, 2022 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 4,958
- views
-
- 521
- downloads
-
- 37
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Whole-brain comparison of rodent and human brains using spatial transcriptomics
eLife 11:e79418.
https://doi.org/10.7554/eLife.79418
Further reading
-
- Biochemistry and Chemical Biology
- Evolutionary Biology
The emergence of new protein functions is crucial for the evolution of organisms. This process has been extensively researched for soluble enzymes, but it is largely unexplored for membrane transporters, even though the ability to acquire new nutrients from a changing environment requires evolvability of transport functions. Here, we demonstrate the importance of environmental pressure in obtaining a new activity or altering a promiscuous activity in members of the amino acid-polyamine-organocation (APC)-type yeast amino acid transporters family. We identify APC members that have broader substrate spectra than previously described. Using in vivo experimental evolution, we evolve two of these transporter genes, AGP1 and PUT4, toward new substrate specificities. Single mutations on these transporters are found to be sufficient for expanding the substrate range of the proteins, while retaining the capacity to transport all original substrates. Nonetheless, each adaptive mutation comes with a distinct effect on the fitness for each of the original substrates, illustrating a trade-off between the ancestral and evolved functions. Collectively, our findings reveal how substrate-adaptive mutations in membrane transporters contribute to fitness and provide insights into how organisms can use transporter evolution to explore new ecological niches.
-
- Evolutionary Biology
- Genetics and Genomics
Copy number variation in large gene families is well characterized for plant resistance genes, but similar studies are rare in animals. The zebrafish (Danio rerio) has hundreds of NLR immune genes, making this species ideal for studying this phenomenon. By sequencing 93 zebrafish from multiple wild and laboratory populations, we identified a total of 1513 NLRs, many more than the previously known 400. Approximately half of those are present in all wild populations, but only 4% were found in 80% or more of the individual fish. Wild fish have up to two times as many NLRs per individual and up to four times as many NLRs per population than laboratory strains. In contrast to the massive variability of gene copies, nucleotide diversity in zebrafish NLR genes is very low: around half of the copies are monomorphic and the remaining ones have very few polymorphisms, likely a signature of purifying selection.
