Analysis of human accelerated DNA regions using archaic hominin genomes
Open accessAbstract
Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The T→A transversion in HAR202 differs from the general trend for HARs, which tend to be identical to their archaic ortholog sequences in 92% of the human/chimp substitutions analyzed.
“This particular T → A transversion differs from the general trend observed for HARs which tend to be identical to their archaic ortholog sequences in 92% of the human/chimp substitutions analyzed (Burbano et al. 2012).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Burbano et al. 2012
92% of the H. sapiens-specific substitutions in HARs are also present in archaic humans.
“It has been reported that 92% of the H. sapiens-specific substitutions in HARs are also present in archaic humans (Burbano et al. 2012).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Burbano et al. 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
A draft sequence of the Neandertal genome
Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., et al. (2010) · Science · doi:10.1126/science.1188021 · Cited by 4,318 · see citing works
Self-citationGenetic history of an archaic hominin group from Denisova Cave in Siberia
Reich, D., Green, R. E., Kircher, M., Krause, J., Patterson, N., Durand, E. Y., Viola, B., Briggs, A. W., Stenzel, U., Johnson, P. L. F., et al. (2010) · Nature · doi:10.1038/nature09710 · Cited by 1,991 · see citing works
Self-citationIn vivo enhancer analysis of human conserved non-coding sequences
Pennacchio, L. A., Ahituv, N., Moses, A. M., Prabhakar, S., Nobrega, M. A., Shoukry, M., Minovitsky, S., Dubchak, I., Holt, A., Lewis, K. D., et al. (2006) · Nature · doi:10.1038/nature05295 · Cited by 1,165 · see citing works
An RNA gene expressed during cortical development evolved rapidly in humans
Pollard, K. S., Salama, S. R., Lambert, N., Lambot, M.-A., Coppens, S., Pedersen, J. S., Katzman, S., King, B., Onodera, C., Siepel, A., et al. (2006) · Nature · doi:10.1038/nature05113 · Cited by 1,005 · see citing works
Self-citationPatterns of damage in genomic DNA sequences from a neandertal
Briggs, A. W., Stenzel, U., Johnson, P. L. F., Green, R. E., Kelso, J., Prüfer, K., Meyer, M., Krause, J., Ronan, M. T., Lachmann, M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0704665104 · Cited by 981 · see citing works
Self-citationGenomic mapping by fingerprinting random clones: A mathematical analysis
Lander, E. S., & Waterman, M. S. (1988) · Genomics · doi:10.1016/0888-7543(88)90007-9 · Cited by 942 · see citing works
Biased gene conversion and the evolution of mammalian genomic landscapes
Duret, L., & Galtier, N. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082908-150001 · Cited by 737 · see citing works
Hofreiter, M. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.23.4793 · Cited by 684 · see citing works
Genome-wide in situ exon capture for selective resequencing
Hodges, E. C., Xuan, Z., Balija, V. S., Kramer, M., Molla, M. N., Smith, S. W., Middle, C. M., Rodesch, M. J., Albert, T. J., Hannon, G. J., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.42 · Cited by 677 · see citing works
High-resolution mapping of meiotic crossovers and non-crossovers in yeast
Mancera, E., Bourgon, R., Brozzi, A., Huber, W. K., & Steinmetz, L. M. (2008) · Nature · doi:10.1038/nature07135 · Cited by 615 · see citing works
A Complete Neandertal Mitochondrial Genome Sequence Determined by High-Throughput Sequencing
Green, R. E., Malaspinas, A., Krause, J., Briggs, A. W., Johnson, P. L. F., Uhler, C., Meyer, M., Good, J. M., Maričić, T., Stenzel, U., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.021 · Cited by 601 · see citing works
Self-citationAncient DNA extraction from bones and teeth
Rohland, N., & Hofreiter, M. (2007) · Nature Protocols · doi:10.1038/nprot.2007.247 · Cited by 584 · see citing works
Forces shaping the fastest evolving regions in the human genome
Pollard, K. S., Salama, S. R., King, B., Kern, A. D., Dreszer, T., Katzman, S., Siepel, A., Pedersen, J. S., Bejerano, G., Baertsch, R., et al. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020168 · Cited by 511 · see citing works
Self-citationTargeted Retrieval and Analysis of Five Neandertal mtDNA Genomes
Briggs, A. W., Good, J. M., Green, R. E., Krause, J., Maričić, T., Stenzel, U., Lalueza‐Fox, C., Rudan, P., Brajković, D., Kućan, Ž., et al. (2009) · Science · doi:10.1126/science.1174462 · Cited by 501 · see citing works
Self-citationRemoval of deaminated cytosines and detection of in vivo methylation in ancient DNA
Briggs, A. W., Stenzel, U., Meyer, M., Krause, J., Kircher, M., & Pääbo, S. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp1163 · Cited by 491 · see citing works
Self-citationAccelerated Evolution of Conserved Noncoding Sequences in Humans
Prabhakar, S., Noonan, J. P., Pääbo, S., & Rubin, E. M. (2006) · Science · doi:10.1126/science.1130738 · Cited by 481 · see citing works
Comparison of Fine-Scale Recombination Rates in Humans and Chimpanzees
Winckler, W., Myers, S. R., Richter, D. J., Onofrio, R. C., McDonald, G. J., Bontrop, R. E., McVean, G., Gabriel, S., Reich, D., Donnelly, P., et al. (2005) · Science · doi:10.1126/science.1105322 · Cited by 357 · see citing works
Human-Specific Gain of Function in a Developmental Enhancer
Prabhakar, S., Visel, A., Akiyama, J. A., Shoukry, M. I., Lewis, K. D., Holt, A., Plajzer-Frick, I., Morrison, H., FitzPatrick, D. R., Afzal, V., et al. (2008) · Science · doi:10.1126/science.1159974 · Cited by 352 · see citing works
The Impact of Recombination on Nucleotide Substitutions in the Human Genome
Duret, L., & Arndt, P. F. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000071 · Cited by 347 · see citing works
Fine-scale recombination patterns differ between chimpanzees and humans
Ptak, S. E., Hinds, D. A., Koehler, K., Nickel, B., Patil, N., Ballinger, D. G., Przeworski, M., Frazer, K. A., & Pääbo, S. (2005) · Nature Genetics · doi:10.1038/ng1529 · Cited by 279 · see citing works
Self-citationTargeted Investigation of the Neandertal Genome by Array-Based Sequence Capture
Burbano, H. A., Hodges, E. C., Green, R. E., Briggs, A. W., Krause, J., Meyer, M., Good, J. M., Maričić, T., Johnson, P. L. F., Xuan, Z., et al. (2010) · Science · doi:10.1126/science.1188046 · Cited by 276 · see citing works
Self-citationAdaptation or biased gene conversion? Extending the null hypothesis of molecular evolution
Galtier, N., & Duret, L. (2007) · Trends in Genetics · doi:10.1016/j.tig.2007.03.011 · Cited by 260 · see citing works
Paleobiology and comparative morphology of a late Neandertal sample from El Sidrón, Asturias, Spain
Rosas, A., Martínez-Maza, C., Bastir, M., García-Tabernero, A., Lalueza-Fox, C., Huguet, R., Ortiz, J. E., Julià, R., Soler, V., de Torres, T., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609662104 · Cited by 223 · see citing works
Self-citationMammalian recombination hot spots: properties, control and evolution
Paigen, K., & Petkov, P. M. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2712 · Cited by 219 · see citing works
Fast-evolving noncoding sequences in the human genome
Bird, C., Stranger, B. E., Liu, M., Thomas, D. J., Ingle, C., Beazley, C., Miller, W., Hurles, M. E., & Dermitzakis, E. T. (2007) · Genome biology · doi:10.1186/gb-2007-8-6-r118 · Cited by 191 · see citing works
Hodges, E. C., Rooks, M. G., Xuan, Z., Bhattacharjee, A., Gordon, D. B., Brizuela, L., McCombie, W. R., & Hannon, G. J. (2009) · Nature Protocols · doi:10.1038/nprot.2009.68 · Cited by 177 · see citing works
Stiller, M., Knapp, M., Stenzel, U., Hofreiter, M., & Meyer, M. (2009) · Genome Research · doi:10.1101/gr.095760.109 · Cited by 122 · see citing works
A genome-wide screen for noncoding elements important in primate evolution
Bush, E., & Lahn, B. T. (2008) · BMC Evolutionary Biology · doi:10.1186/1471-2148-8-17 · Cited by 106 · see citing works
Torres, T., Ortíz, J. E., Grün, R., Eggins, S. M., Valladas, H., Mercier, N., Tisnérat‐Laborde, N., Julià, R., Soler, V., MARTÍNEZ, E., et al. (2009) · Archaeometry · doi:10.1111/j.1475-4754.2009.00491.x · Cited by 86 · see citing works
Self-citationDittmer, S., Kovács, Z., Yuan, S. H., et al. (2010) · Journal of Cell Science · doi:10.1242/jcs.068759 · Cited by 84 · see citing works
Excavation protocol of bone remains for Neandertal DNA analysis in El Sidrón Cave (Asturias, Spain)
Fortea, J., Vives, M. D. L. R., García‐Tabernero, A., Gigli, E., Rosas, A., & Lalueza‐Fox, C. (2008) · Journal of Human Evolution · doi:10.1016/j.jhevol.2008.03.005 · Cited by 53 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
DNA analysis of an early modern human from Tianyuan Cave, China
Fu, Q., Meyer, M., Gao, X., Stenzel, U., Burbano, H. A., Kelso, J., & Pääbo, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221359110 · Cited by 608 · see citing works
Self-citationEvolution of the Human Nervous System Function, Structure, and Development
Sousa, A. M. M., Meyer, K. A., Santpere, G., Gulden, F. O., & Sestan, N. (2017) · Cell · doi:10.1016/j.cell.2017.06.036 · Cited by 517 · see citing works
Many human accelerated regions are developmental enhancers
Capra, J. A., Erwin, G. D., McKinsey, G., Rubenstein, J. L. R., & Pollard, K. S. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0025 · Cited by 235 · see citing works
Self-citationCaporale, A. L., Cinalli, A. R., Rubinstein, M., & Franchini, L. F. (2024) · Molecular Biology and Evolution · doi:10.1093/molbev/msae186 · Cited by 7 · see citing works
“This particular T → A transversion differs from the general trend observed for HARs which tend to be identical to their archaic ortholog sequences in 92% of the human/chimp substitutions analyzed (Burbano et al. 2012).”
Background
- Authors
- Burbano, H. A., Green, R. E., Maricic, T., Lalueza-Fox, C., de la Rasilla, M., Rosas, A., Kelso, J., Pollard, K. S., Lachmann, M., & Pääbo, S.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- University of California, Santa Cruz (US)
- Consejo Superior de Investigaciones Científicas (ES)
- Gladstone Institutes (US)
- Corresponding author
- Burbano, Hernán A.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-03-07
- Volume
- 7
- Issue
- 3
- Pages
- e32877
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3296746
- OpenAlex
- W2131234958
- Cited by
- 46
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 1 · 2013: 5 · 2012: 2
- FWCI
- 19.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (publishedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
- Funders
- Gladstone Institutes
- Searle Scholars Program
- Max-Planck-Gesellschaft
- Universidad de Oviedo
- National Institute of General Medical Sciences (R01GM082901, GM082901)
- Topics
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- human accelerated regions, archaic humans, Neanderthals, adaptive evolution, biased gene conversion, allele fixation
- MeSH terms
- Adaptation, Biological, Animals, DNA, Humans, Male, Mutation, Hominidae, Genome, Human, Cluster Analysis, Genome, Evolution, Molecular, Neanderthals
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
