Accelerated Evolution of Conserved Noncoding Sequences in Humans
Abstract
Changes in gene regulation likely influenced the profound phenotypic divergence of humans from other mammals, but the extent of adaptive substitution in human regulatory sequences remains unknown. We identified 992 conserved noncoding sequences (CNSs) with a significant excess of human-specific substitutions. These accelerated elements were disproportionately found near genes involved in neuronal cell adhesion. To assess the uniqueness of human noncoding evolution, we examined CNSs accelerated in chimpanzee and mouse. Although we observed a similar enrichment near neuronal adhesion genes in chimpanzee, the accelerated CNSs themselves exhibited almost no overlap with those in human, suggesting independent evolution toward different neuronal phenotypes in each species. CNSs accelerated in mouse showed no bias toward neuronal cell adhesion. Our results indicate that widespread cis-regulatory changes in human evolution may have contributed to uniquely human features of brain development and function.
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Genes near haCNSs are particularly likely to show differential expression between regions of developing human neocortex, suggesting transcriptional regulation by haCNSs may be important in human-specific neurodevelopment.
“Genes near CNSs with significantly accelerated rates of substitution in the human lineage (haCNSs)15 are particularly likely to show differential expression between regions of developing human neocortex3,5, suggesting transcriptional regulation by haCNSs may be important in human-specific neurodevelopment.”
From Transcriptional landscape of the prenatal human brain (2014) · cites this paper as [15]
Profiling of mid-gestational human brain identified many genes differentially expressed between major regions, including genes associated with human-accelerated conserved noncoding sequences.
“Profiling of mid-gestational human brain3,5 identified many genes differentially expressed between major regions, including genes associated with human-accelerated conserved noncoding sequences (haCNSs)15.”
From Transcriptional landscape of the prenatal human brain (2014) · cites this paper as [15]
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- Authors
- Prabhakar, S., Noonan, J. P., Pääbo, S., & Rubin, E. M.
- Affiliations
- United States Department of Energy (US)
- U.S. Department of Energy (DOE) Joint Genome Institute, Walnut Creek, CA 94598, USA.
- Corresponding author
- Prabhakar, Shyam
- Noonan, James P.
- Rubin, Edward M.
- Venue
- Science
- Published
- 2006-11-03
- Volume
- 314
- Issue
- 5800
- Pages
- 786-786
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2060256600
- Cited by
- 481
- References
- 2
- Citations by year
- 2026: 21 · 2025: 19 · 2024: 26 · 2023: 30 · 2022: 20 · 2021: 18 · 2020: 26 · 2019: 12 · 2018: 18 · 2017: 26 · 2016: 15 · 2015: 33 · 2014: 21 · 2013: 31 · 2012: 23
- FWCI
- 34.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-066681, U01HL066681)
- National Institute of General Medical Sciences (F32GM074367, 1-F32-GM074367)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- conserved non-coding elements, cis-regulatory elements, human evolution, adaptive substitutions, gene expression regulation, chimpanzees, mice, brain development, phenotypic divergence
- MeSH terms
- Animals, Base Sequence, Brain, Cell Adhesion, Pan troglodytes, Cognition, Humans, Neurons, Regulatory Sequences, Nucleic Acid, Cell Adhesion Molecules, Genome, Human, Conserved Sequence, Evolution, Molecular, DNA, Intergenic, Mice
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