Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions
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No More Junk DNA: The majority of the human genome is transcribed at some level, but the function and evolutionary constraint among regions that do not regulate gene expression or code for genes are generally unknown. Examining data from the 1000 Genomes Project and ENCODE, Ward and Kellis (p. 1675 , published online 5 September) examined regions of the human genome that did not show conservation among mammals and found evidence for a human lineage-specific constraint spanning approximately 4% of the genome that is biochemically active but not directly associated with genes. Interestingly, these regions showed lower numbers of single-nucleotide polymorphisms, heterozygosity, and derived allele frequencies, suggesting that they are under constraint and may be functional.
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Previous studies have shown that while polygenic risk scores and eQTLs have limited cross-population portability, biochemically active functional regulatory elements tend to be under evolutionary constraint within the human lineage.
“Previous studies have shown that, while polygenic risk scores [65] and eQTLs [66] have limited cross-population portability, biochemically active functional regulatory elements tend to be under evolutionary constraint within the human lineage [67, 68].”
From Denisovan introgression has shaped the immune system of present-day Papuans (2022) · cites this paper as [67]
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Self-citation
- Authors
- Ward, L. D., & Kellis, M.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Kellis, Manolis
- Venue
- Science
- Published
- 2012-09-28
- Volume
- 337
- Issue
- 6102
- Pages
- 1675-1678
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4104271
- OpenAlex
- W2166898061
- Cited by
- 209
- References
- 42
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 11 · 2017: 10 · 2016: 18 · 2015: 27 · 2014: 32 · 2013: 37 · 2012: 5
- FWCI
- 19.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
- PMC
- Funders
- National Science Foundation (0644282, CAREER)
- National Institutes of Health
- National Human Genome Research Institute (RC1HG005334, R01HG004037)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- 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
- Keywords
- purifying selection, regulatory elements, human genome evolution, 1000 Genomes Project, human genetic variation
- MeSH terms
- Disease, Gene Expression Regulation, Humans, Regulatory Sequences, Nucleic Acid, Selection, Genetic, Transcription, Genetic, Genetic Variation, Genome, Human, Conserved Sequence, Polymorphism, Single Nucleotide
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