Tempo and mode of gene expression evolution in the brain across primates
- University of Massachusetts Amherst, United States
- MAEBIOS, United States
- Kent State University, United States
- The University of Texas MD Anderson Cancer Center, United States
- Icahn School of Medicine at Mount Sinai, United States
- George Washington University, United States
- Washington University in St. Louis, United States
Abstract
Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species (Barton, 2012; DeCasien & Higham, 2019; Powell, Isler, & Barton, 2017). Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date (e.g. Khaitovich et al., 2005; Khrameeva et al., 2020; Ma et al., 2022; Somel et al., 2009). To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-Seq data from four brain regions in an unprecedented eighteen species. Here we show a remarkable level of variation in gene expression among hominid species, including humans and chimpanzees, despite their relatively recent divergence time from other primates. We found that individual genes display a wide range of expression dynamics across evolutionary time reflective of the diverse selection pressures acting on genes within primate brain tissue. Using our samples that represents a 190-fold difference in primate brain size, we identified genes with variation in expression most correlated with brain size. Our study extensively broadens the phylogenetic context of what is known about the molecular evolution of the brain across primates and identifies novel candidate genes for study of genetic regulation of brain evolution.
Data availability
Sequencing data have been deposited in the Short Read Archive: BioProject PRJNA639850
-
RNA-Seq of human astrocytesNCBI Gene Expression Omnibus, GSE73721.
-
single cell RNA-seq from pyramidal cell (ENCLB928LID)NCBI Gene Expression Omnibus, GSE78331.
Article and author information
Author details
Courtney C Babbitt
Funding
National Science Foundation (BCS-1750377)
- Courtney C Babbitt
National Institutes of Health (T32 GM135096)
- Katherine Rickelton
James S. McDonnell Foundation (220020293)
- Chet C Sherwood
National Institutes of Health (NS-092988)
- Chet C Sherwood
National Science Foundation (SMA-1542848)
- Chet C Sherwood
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jenny Tung, Duke University, United States
Version history
- Preprint posted: April 21, 2021 (view preprint)
- Received: May 12, 2021
- Accepted: January 25, 2024
- Accepted Manuscript published: January 26, 2024 (version 1)
- Version of Record published: February 19, 2024 (version 2)
Copyright
© 2024, Rickelton et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 1,352
- views
-
- 239
- downloads
-
- 0
- 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)
Tempo and mode of gene expression evolution in the brain across primates
eLife 13:e70276.
https://doi.org/10.7554/eLife.70276
Further reading
-
- Chromosomes and Gene Expression
- Genetics and Genomics
ASARs are a family of very-long noncoding RNAs that control replication timing on individual human autosomes, and are essential for chromosome stability. The eight known ASAR lncRNAs remain closely associated with their parent chromosomes. Analysis of RNA-protein interaction data (from ENCODE) revealed numerous RBPs with significant interactions with multiple ASAR lncRNAs, with several hnRNPs as abundant interactors. An ~7 kb domain within the ASAR6-141 lncRNA shows a striking density of RBP interaction sites. Genetic deletion and ectopic integration assays indicate that this ~7 kb RNA binding protein domain contains functional sequences for controlling replication timing of entire chromosomes in cis. shRNA-mediated depletion of 10 different RNA binding proteins, including HNRNPA1, HNRNPC, HNRNPL, HNRNPM, HNRNPU, or HNRNPUL1, results in dissociation of ASAR lncRNAs from their chromosome territories, and disrupts the synchronous replication that occurs on all autosome pairs, recapitulating the effect of individual ASAR knockouts on a genome-wide scale. Our results further demonstrate the role that ASARs play during the temporal order of genome-wide replication, and we propose that ASARs function as essential RNA scaffolds for the assembly of hnRNP complexes that help maintain the structural integrity of each mammalian chromosome.
-
- Chromosomes and Gene Expression
Eukaryotic chromatin is organized into functional domains, that are characterized by distinct proteomic compositions and specific nuclear positions. In contrast to cellular organelles surrounded by lipid membranes, the composition of distinct chromatin domains is rather ill described and highly dynamic. To gain molecular insight into these domains and explore their composition, we developed an antibody-based proximity biotinylation method targeting the RNA and proteins constituents. The method that we termed antibody-mediated proximity labelling coupled to mass spectrometry (AMPL-MS) does not require the expression of fusion proteins and therefore constitutes a versatile and very sensitive method to characterize the composition of chromatin domains based on specific signature proteins or histone modifications. To demonstrate the utility of our approach we used AMPL-MS to characterize the molecular features of the chromocenter as well as the chromosome territory containing the hyperactive X chromosome in Drosophila. This analysis identified a number of known RNA-binding proteins in proximity of the hyperactive X and the centromere, supporting the accuracy of our method. In addition, it enabled us to characterize the role of RNA in the formation of these nuclear bodies. Furthermore, our method identified a new set of RNA molecules associated with the Drosophila centromere. Characterization of these novel molecules suggested the formation of R-loops in centromeres, which we validated using a novel probe for R-loops in Drosophila. Taken together, AMPL-MS improves the selectivity and specificity of proximity ligation allowing for novel discoveries of weak protein–RNA interactions in biologically diverse domains.
