Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

The functional and evolutionary impacts of human-specific deletions in conserved elements

James R. Xue, Ava Mackay-Smith, Kousuke Mouri, Meilín Fernández García, Michael X. Dong, Jared F. Akers, Mark Noble, Xue Li, Kerstin Lindblad‐Toh, Elinor K. Karlsson, James P. Noonan, Terence D. Capellini, Kristen Brennand, Ryan Tewhey, Pardis C. Sabeti, Steven K. Reilly, Gregory Andrews, Joel Armstrong, Matteo Bianchi, Bruce W. Birren, Kevin R. Bredemeyer, Ana M. Breit, Matthew J. Christmas, Hiram Clawson, Joana Damas, Federica Di Palma, Mark Diekhans, Michael X. Dong, Eduardo Eizirik, Kaili Fan, Cornelia Fanter, Nicole M. Foley, Karin Forsberg‐Nilsson, Carlos J. Garcia, John Gatesy, Steven Gazal, Diane P. Genereux, Linda Goodman, Jenna Grimshaw, Michaela K. Halsey, Andrew J. Harris, Glenn Hickey, Michael Hiller, Allyson G. Hindle, Robert Hubley, Graham M. Hughes, Jeremy Johnson, David Juan, Irene M. Kaplow, Elinor K. Karlsson, Kathleen C. Keough, Bogdan Kirilenko, Klaus‐Peter Koepfli, Jennifer M. Korstian, Amanda Kowalczyk, Sergey V. Kozyrev, Alyssa J. Lawler, Colleen Lawless, Thomas Lehmann, Danielle L. Levesque, Harris A. Lewin, Xue Li, Abigail Lind, Kerstin Lindblad‐Toh, Ava Mackay-Smith, Voichita D. Marinescu, Tomàs Marquès‐Bonet, Victor C. Mason, Jennifer R. S. Meadows, Wynn K. Meyer, Jill E. Moore, Lucas R. Moreira, Diana D. Moreno-Santillán, Kathleen M. Morrill, Gerard Muntané, William J. Murphy, Arcadi Navarro, Martin Nweeia, Sylvia Ortmann, Austin Osmanski, Benedict Paten, Nicole S. Paulat, Andreas Pfenning, BaDoi N. Phan, Katherine S. Pollard, Henry Pratt, David A. Ray, Steven K. Reilly, Jeb Rosen, Irina Ruf, Louise Ryan, Oliver A. Ryder, Pardis C. Sabeti, Daniel E. Schäffer, Aitor Serres, Beth Shapiro, Arian F. A. Smit, Mark S. Springer, Chaitanya Srinivasan, Cynthia Steiner

Science · 2023

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Summary

This study identifies and characterises 10,032 human-specific conserved deletions (hCONDELs) that may contribute to uniquely human phenotypic traits. Using massively parallel reporter assays across six cell types, the authors demonstrate that approximately 800 of these deletions confer significant regulatory activity differences, with notably half enhancing rather than disrupting function. The work provides functional and evolutionary insights into brain development genes, suggesting these deletions may have shaped human-specific neurodevelopmental pathways.

Regional applicability

This is fundamental genomic research with no direct application to farming systems, soil health, agricultural policy, or food production in the United Kingdom or elsewhere. The findings relate to human evolutionary biology and are not applicable to agricultural or nutritional practice.

Key measures

Number of human-specific conserved deletions identified (10,032); average deletion length (2.56 base pairs); number of hCONDELs with significant regulatory activity differences (800); regulatory activity direction (enhancement vs. disruption); gene expression changes in myelination and synaptic function genes

Outcomes reported

The study identified and functionally characterised 10,032 human-specific conserved deletions (hCONDELs) using massively parallel reporter assays and demonstrated that 800 of these deletions have significant regulatory activity differences, with half enhancing rather than disrupting function. Several hCONDELs were shown to have putative effects on brain development genes including HDAC5, CPEB4, and PPP2CA.

Theme
General food systems / other
Subject
Out of scope / non-food
Study type
Research
Study design
Comparative genomic analysis with functional validation
Source type
Peer-reviewed study
Status
Published
System type
Other
DOI
10.1126/science.abn2253
Catalogue ID
SNmq64d90a-3ltg9n

Topic tags

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