The cis-regulatory effects of modern human-specific variants
The Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-04-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/63713 |
| _version_ | 1811202864913055744 |
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| author | Carly V Weiss Lana Harshman Fumitaka Inoue Hunter B Fraser Dmitri A Petrov Nadav Ahituv David Gokhman |
| author_facet | Carly V Weiss Lana Harshman Fumitaka Inoue Hunter B Fraser Dmitri A Petrov Nadav Ahituv David Gokhman |
| author_sort | Carly V Weiss |
| collection | DOAJ |
| description | The Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in ancient samples. Here, we used a massively parallel reporter assay in embryonic stem cells, neural progenitor cells, and bone osteoblasts to investigate the regulatory effects of the 14,042 single-nucleotide modern human-specific variants. Overall, 1791 (13%) of sequences containing these variants showed active regulatory activity, and 407 (23%) of these drove differential expression between human groups. Differentially active sequences were associated with divergent transcription factor binding motifs, and with genes enriched for vocal tract and brain anatomy and function. This work provides insight into the regulatory function of variants that emerged along the modern human lineage and the recent evolution of human gene expression. |
| first_indexed | 2024-04-12T02:46:11Z |
| format | Article |
| id | doaj.art-520e8dbcbf6e4facbbf3b746d9fe8d9f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:46:11Z |
| publishDate | 2021-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-520e8dbcbf6e4facbbf3b746d9fe8d9f2022-12-22T03:51:10ZengeLife Sciences Publications LtdeLife2050-084X2021-04-011010.7554/eLife.63713The cis-regulatory effects of modern human-specific variantsCarly V Weiss0Lana Harshman1Fumitaka Inoue2https://orcid.org/0000-0003-0657-434XHunter B Fraser3https://orcid.org/0000-0001-8400-8541Dmitri A Petrov4https://orcid.org/0000-0002-3664-9130Nadav Ahituv5https://orcid.org/0000-0002-7434-8144David Gokhman6https://orcid.org/0000-0002-3536-9006Department of Biology, Stanford University, Stanford, Stanford, United StatesDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, San Francisco, United States; Institute for Human Genetics, University of California San Francisco, San Francisco, San Francisco, United StatesDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, San Francisco, United States; Institute for Human Genetics, University of California San Francisco, San Francisco, San Francisco, United StatesDepartment of Biology, Stanford University, Stanford, Stanford, United StatesDepartment of Biology, Stanford University, Stanford, Stanford, United StatesDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, San Francisco, United States; Institute for Human Genetics, University of California San Francisco, San Francisco, San Francisco, United StatesDepartment of Biology, Stanford University, Stanford, Stanford, United StatesThe Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in ancient samples. Here, we used a massively parallel reporter assay in embryonic stem cells, neural progenitor cells, and bone osteoblasts to investigate the regulatory effects of the 14,042 single-nucleotide modern human-specific variants. Overall, 1791 (13%) of sequences containing these variants showed active regulatory activity, and 407 (23%) of these drove differential expression between human groups. Differentially active sequences were associated with divergent transcription factor binding motifs, and with genes enriched for vocal tract and brain anatomy and function. This work provides insight into the regulatory function of variants that emerged along the modern human lineage and the recent evolution of human gene expression.https://elifesciences.org/articles/63713expressionNeanderthalDenisovanapeMPRASNP |
| spellingShingle | Carly V Weiss Lana Harshman Fumitaka Inoue Hunter B Fraser Dmitri A Petrov Nadav Ahituv David Gokhman The cis-regulatory effects of modern human-specific variants eLife expression Neanderthal Denisovan ape MPRA SNP |
| title | The cis-regulatory effects of modern human-specific variants |
| title_full | The cis-regulatory effects of modern human-specific variants |
| title_fullStr | The cis-regulatory effects of modern human-specific variants |
| title_full_unstemmed | The cis-regulatory effects of modern human-specific variants |
| title_short | The cis-regulatory effects of modern human-specific variants |
| title_sort | cis regulatory effects of modern human specific variants |
| topic | expression Neanderthal Denisovan ape MPRA SNP |
| url | https://elifesciences.org/articles/63713 |
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