Using the Neandertal genome to study the evolution of small insertions and deletions in modern humans
Open accessAbstract
BACKGROUND: Small insertions and deletions occur in humans at a lower rate compared to nucleotide changes, but evolve under more constraint than nucleotide changes. While the evolution of insertions and deletions have been investigated using ape outgroups, the now available genome of a Neandertal can shed light on the evolution of indels in more recent times. RESULTS: We used the Neandertal genome together with several primate outgroup genomes to differentiate between human insertion/deletion changes that likely occurred before the split from Neandertals and those that likely arose later. Changes that pre-date the split from Neandertals show a smaller proportion of deletions than those that occurred later. The presence of a Neandertal-shared allele in Europeans or Asians but the absence in Africans was used to detect putatively introgressed indels in Europeans and Asians. A larger proportion of these variants reside in intergenic regions compared to other modern human variants, and some variants are linked to SNPs that have been associated with traits in modern humans. CONCLUSIONS: Our results are in agreement with earlier results that suggested that deletions evolve under more constraint than insertions. When considering Neandertal introgressed variants, we find some evidence that negative selection affected these variants more than other variants segregating in modern humans. Among introgressed variants we also identify indels that may influence the phenotype of their carriers. In particular an introgressed deletion associated with a decrease in the time to menarche may constitute an example of a former Neandertal-specific trait contributing to modern human phenotypic diversity.
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?
An introgressed indel from Neanderthals causes an earlier onset of menarche in present-day humans, supporting at least the existence of alleles for earlier maturation in the Neanderthal population.
“an introgressed indel from Neanderthals causes an earlier onset of menarche in present-day humans30, supporting at least the existence of alleles for earlier maturation in the Neanderthal population.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [30]
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
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247 · see citing works
A general framework for estimating the relative pathogenicity of human genetic variants
Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014) · Nature Genetics · doi:10.1038/ng.2892 · Cited by 6,183 · see citing works
Adaptive protein evolution at the Adh locus in Drosophila
McDonald, J. H., & Kreitman, M. (1991) · Nature · doi:10.1038/351652a0 · Cited by 3,320 · see citing works
Initial sequence of the chimpanzee genome and comparison with the human genome
The Chimpanzee Sequencing and Analysis Consortium (2005) · Nature · doi:10.1038/nature04072 · Cited by 2,459 · see citing works
The complete genome sequence of a Neanderthal from the Altai Mountains
Prüfer, K., Racimo, F., Patterson, N., Jay, F., Sankararaman, S., Sawyer, S., Heinze, A., Renaud, G., Sudmant, P. H., de Filippo, C., et al. (2014) · Nature · doi:10.1038/nature12886 · Cited by 2,254 · see citing works
Self-citationDeriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor
McLaren, W. M., Yates, B., Ríos, D., Chen, Y., Flicek, P., & Cunningham, F. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq330 · Cited by 1,586 · see citing works
The Simons Genome Diversity Project: 300 genomes from 142 diverse populations
Mallick, S., Li, H., Lipson, M., Mathieson, I., Gymrek, M., Racimo, F., Zhao, M., Chennagiri, N., Nordenfelt, S., Tandon, A., et al. (2016) · Nature · doi:10.1038/nature18964 · Cited by 1,584 · see citing works
Aligning Multiple Genomic Sequences With the Threaded Blockset Aligner
Blanchette, M., Kent, W. J., Riemer, C., Elnitski, L., Smit, A. F. A., Roskin, K. M., Baertsch, R., Rosenbloom, K., Clawson, H., Green, E. D., et al. (2004) · Genome Research · doi:10.1101/gr.1933104 · Cited by 1,452 · see citing works
Evolutionary and biomedical insights from the rhesus macaque genome.
Gibbs, R. A., Rogers, J., Katze, M. G., Bumgarner, R., Weinstock, G. M., Mardis, E. R., Remington, K. A., Strausberg, R. L., Venter, J. C., Wilson, R. K., et al. (2007) · Science · doi:10.1126/science.1139247 · Cited by 1,403 · see citing works
Ancient human genomes suggest three ancestral populations for present-day Europeans
Lazaridis, I., Patterson, N., Mittnik, A., Renaud, G., Mallick, S., Kirsanow, K., Sudmant, P. H., Schraiber, J. G., Castellano, S., Lipson, M., et al. (2014) · Nature · doi:10.1038/nature13673 · Cited by 1,357 · see citing works
Self-citationAltitude adaptation in Tibetans caused by introgression of Denisovan-like DNA
Huerta-Sánchez, E., Jin, X., Asan, Bianba, Z., Peter, B. M., Vinckenbosch, N., Liang, Y., Yi, X., He, M., Somel, M., et al. (2014) · Nature · doi:10.1038/nature13408 · Cited by 1,208 · see citing works
Cunningham, F., Amode, M. R., Barrell, D., Beal, K., Billis, K., Brent, S., Carvalho-Silva, D., Clapham, P., Coates, G., Fitzgerald, S., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gku1010 · Cited by 1,115 · see citing works
The genomic landscape of Neanderthal ancestry in present-day humans
Sankararaman, S., Mallick, S., Dannemann, M., Prüfer, K., Kelso, J., Pääbo, S., Patterson, N., & Reich, D. (2014) · Nature · doi:10.1038/nature12961 · Cited by 1,107 · see citing works
Self-citationSeven new loci associated with age-related macular degeneration
The AMD Gene Consortium (2013) · Nature Genetics · doi:10.1038/ng.2578 · Cited by 788 · see citing works
Insights into hominid evolution from the gorilla genome sequence
Scally, A., Dutheil, J. Y., Hillier, L. W., Jordan, G. E., Goodhead, I., Herrero, J., Hobolth, A., Lappalainen, T., Mailund, T., Marquès‐Bonet, T., et al. (2012) · Nature · doi:10.1038/nature10842 · Cited by 760 · see citing works
Positive and Negative Selection on the Human Genome
Fay, J. C., Wyckoff, G. J., & Wu, C. (2001) · Genetics · doi:10.1093/genetics/158.3.1227 · Cited by 646 · see citing works
Cho, Y. S., Chen, C.-H., Hu, C., Ong, R. T., Ong, R. T. H., Sim, X., Takeuchi, F., Wu, Y., Go, M. J., Yamauchi, T., et al. (2011) · Nature Genetics · doi:10.1038/ng.1019 · Cited by 607 · see citing works
Comparative and demographic analysis of orang-utan genomes
Locke, D. P., Hillier, L. W., Warren, W. C., Worley, K. C., Nazareth, L. V., Muzny, D. M., Yang, S., Wang, Z., Chinwalla, A., Minx, P., et al. (2011) · Nature · doi:10.1038/nature09687 · Cited by 598 · see citing works
Beaty, T. H., Murray, J. C., Marazita, M. L., Munger, R. G., Ruczinski, I., Hetmanski, J. B., Liang, K., Wu, T., Murray, T., Fallin, M. D., et al. (2010) · Nature Genetics · doi:10.1038/ng.580 · Cited by 583 · see citing works
The bonobo genome compared with the chimpanzee and human genomes
Prüfer, K., Munch, K., Hellmann, I., Akagi, K., Miller, J. R., Walenz, B., Koren, S., Sutton, G., Kodira, C., Winer, R., et al. (2012) · Nature · doi:10.1038/nature11128 · Cited by 579 · see citing works
Self-citationResurrecting Surviving Neandertal Lineages from Modern Human Genomes
Vernot, B., & Akey, J. M. (2014) · Science · doi:10.1126/science.1245938 · Cited by 562 · see citing works
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
The GIANT Consortium, Elks, C. E., Perry, J. R. B., Sulem, P., Chasman, D. I., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., et al. (2010) · Nature Genetics · doi:10.1038/ng.714 · Cited by 504 · see citing works
Recent and ongoing selection in the human genome
Nielsen, R., Hellmann, I., Hubisz, M. J., Bustamante, C. D., & Clark, A. G. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2187 · Cited by 501 · see citing works
The Date of Interbreeding between Neandertals and Modern Humans
Sankararaman, S., Patterson, N., Li, H., Pääbo, S., & Reich, D. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002947 · Cited by 460 · see citing works
The UCSC Genome Browser database: 2016 update
Speir, M. L., Zweig, A. S., Rosenbloom, K. R., Raney, B. J., Paten, B., Nejad, P., Lee, B. T., Learned, K., Karolchik, D., Hinrichs, A. S., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1275 · Cited by 451 · see citing works
The Genetic Cost of Neanderthal Introgression
Harris, K., & Nielsen, R. (2016) · Genetics · doi:10.1534/genetics.116.186890 · Cited by 419 · see citing works
Gibbon genome and the fast karyotype evolution of small apes
Carbone, L., Harris, R. A., Gnerre, S., Veeramah, K. R., Lorente-Galdós, B., Huddleston, J., Meyer, T. J., Herrero, J., Roos, C., Aken, B. L., et al. (2014) · Nature · doi:10.1038/nature13679 · Cited by 360 · see citing works
Small insertions and deletions (INDELs) in human genomes
Mullaney, J. M., Mills, R. E., Pittard, W. S., & Devine, S. E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq400 · Cited by 353 · see citing works
Dental evidence for ontogenetic differences between modern humans and Neanderthals
Smith, T. M., Tafforeau, P., Reid, D. J., Pouech, J., Lazzari, V., Zermeno, J. P., Guatelli-Steinberg, D., Olejniczak, A. J., Hoffman, A., Radovčić, J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010906107 · Cited by 331 · see citing works
The landscape of recombination in African Americans
Hinch, A. G., Tandon, A., Patterson, N. J., Song, Y., Rohland, N., Palmer, C. D., Chen, G. K., Wang, K., Buxbaum, S. G., Akylbekova, E. L., et al. (2011) · Nature · doi:10.1038/nature10336 · Cited by 311 · see citing works
The Strength of Selection against Neanderthal Introgression
Juric, I., Aeschbacher, S., & Coop, G. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1006340 · Cited by 309 · see citing works
Surprisingly rapid growth in Neanderthals
Ramirez Rozzi, F. V., & Bermudez de Castro, J. M. (2004) · Nature · doi:10.1038/nature02428 · Cited by 289 · see citing works
Natural genetic variation caused by small insertions and deletions in the human genomePreprint
Mills, R. E., Pittard, W. S., Mullaney, J. M., Farooq, U., Creasy, T. H., Mahurkar, A., Kemeza, D. M., Strassler, D. S., Ponting, C. P., Webber, C., et al. (2011) · Genome Research · doi:10.1101/gr.115907.110 · Cited by 264 · see citing works
The common marmoset genome provides insight into primate biology and evolution
Worley, K. C., Rogers, J., Muzny, D. M., Weinstock, G. M., Chandrabose, M. N., Cree, A., Dao, M., Dinh, H. H., Fowler, R. G., Gabisi, R. A., et al. (2014) · Nature Genetics · doi:10.1038/ng.3042 · Cited by 261 · see citing works
Deschamps, M., Laval, G., Fagny, M., Itan, Y., Abel, L., Casanova, J.-L., Patin, E., & Quintana-Murci, L. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.014 · Cited by 257 · see citing works
Montgomery, S. B., Goode, D. L., Kvikstad, E. M., Albers, C. A., Zhang, Z. D., Mu, X. J., Ananda, G., Howie, B., Karczewski, K. J., Smith, K. S., et al. (2013) · Genome Research · doi:10.1101/gr.148718.112 · Cited by 253 · see citing works
Dannemann, M., Andrés, A. M., & Kelso, J. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.015 · Cited by 249 · see citing works
Self-citationGWASdb: a database for human genetic variants identified by genome-wide association studies
Li, M. J., Wang, P., Liu, X., Lim, E. L., Wang, Z., Yeager, M., Wong, M. P., Sham, P. C., Chanock, S. J., & Wang, J. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1182 · Cited by 212 · see citing works
Archaic Hominin Admixture Facilitated Adaptation to Out-of-Africa Environments
Gittelman, R. M., Schraiber, J. G., Vernot, B., Mikacenic, C., Wurfel, M. M., & Akey, J. M. (2016) · Current Biology · doi:10.1016/j.cub.2016.10.041 · Cited by 181 · see citing works
FUNC: a package for detecting significant associations between gene sets and ontological annotations
Prüfer, K., Muetzel, B., Do, H.-H., Weiss, G., Khaitovich, P., Rahm, E., Pääbo, S., Lachmann, M., & Enard, W. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-41 · Cited by 173 · see citing works
Self-citationMendez, F. L., Watkins, J. C., & Hammer, M. F. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.06.015 · Cited by 156 · see citing works
Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients
Perlis, R. H., Huang, J., Purcell, S., D, M. F. M., Rush, A. J., Sullivan, P. F., Hamilton, S. P., McMahon, F. J., Schulze, T. G., Potash, J. B., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10040541 · Cited by 147 · see citing works
Sarkissian, C. S. I. D., Allentoft, M. E., Ávila‐Arcos, M. C., Barnett, R., Campos, P. F., Cappellini, E., Ermini, L., Fernández, R., da Fonseca, R. R., Ginolhac, A., et al. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0387 · Cited by 144 · see citing works
Patterns and rates of indel evolution in processed pseudogenes from humans and murids
Ophir, R., & Graur, D. (1997) · Gene · doi:10.1016/s0378-1119(97)00398-3 · Cited by 134 · see citing works
Context of deletions and insertions in human coding sequences
Kondrashov, A. S., & Rogozin, I. B. (2004) · Human Mutation · doi:10.1002/humu.10312 · Cited by 104 · see citing works
Archaic adaptive introgression in <i>TBX15/WARS2</i>
Racimo, F., Gokhman, D., Fumagalli, M., Ko, A., Hansen, T., Moltke, I., Albrechtsen, A., Carmel, L., Huerta-Sánchez, E., & Nielsen, R. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw283 · Cited by 101 · see citing works
Performance evaluation of indel calling tools using real short-read data
Hasan, M. S., Wu, X., & Zhang, L. (2015) · Human Genomics · doi:10.1186/s40246-015-0042-2 · Cited by 95 · see citing works
Analysis of insertion-deletion from deep-sequencing data: software evaluation for optimal detection
Neuman, J. A., Isakov, O., & Shomron, N. (2012) · Briefings in Bioinformatics · doi:10.1093/bib/bbs013 · Cited by 95 · see citing works
Chen, G., Bentley, A. R., Adeyemo, A., Shriner, D., Zhou, J., Doumatey, A. P., Huang, H., Ramos, E., Erdos, M. R., Gerry, N. P., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds282 · Cited by 83 · see citing works
Matthee, C. A., Eick, G. N., Willows‐Munro, S., et al. (2006) · Molecular Phylogenetics and Evolution · doi:10.1016/j.ympev.2006.10.002 · Cited by 62 · see citing works
White, M. J., Risse-Adams, O. S., Goddard, P. C., Contreras, M. G., Adams, J., Hu, D., Eng, C. S., Oh, S. S., Davis, A. J., Meade, K. E., et al. (2016) · Immunogenetics · doi:10.1007/s00251-016-0914-1 · Cited by 61 · see citing works
Beaty, T. H., Murray, J. C., Marazita, M. L., et al. (2010) · Nature Genetics · doi:10.1038/ng0810-727 · Cited by 59 · see citing works
A Macaque's-Eye View of Human Insertions and Deletions: Differences in Mechanisms
Kvikstad, E. M., Tyekucheva, S., Chiaromonte, F., & Makova, K. D. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030176 · Cited by 58 · see citing works
Patterns of Insertion and Deletion in Mammalian Genomes
Tao, S., Fan, Y., Wang, W., et al. (2007) · Current Genomics · doi:10.2174/138920207783406479 · Cited by 55 · see citing works
A Genome-Wide Association Study of Circulating Galectin-3
de Boer, R. A., Verweij, N., van Veldhuisen, D. J., Westra, H.-J., Bakker, S. J. L., Gansevoort, R. T., Kobold, A. C. M., van Gilst, W. H., Franke, L., Leach, I. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047385 · Cited by 49 · see citing works
The Evolution and Functional Impact of Human Deletion Variants Shared with Archaic Hominin Genomes
Lin, Y., Pavlidis, P., Karakoç, E., Ajay, J., & Gökçümen, Ö. (2015) · Molecular Biology and Evolution · doi:10.1093/molbev/msu405 · Cited by 46 · see citing works
Insertion and Deletion Processes in Recent Human History
Sjödin, P., Bataillon, T. M., & Schierup, M. H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008650 · Cited by 41 · see citing works
Large-Scale Parsimony Analysis of Metazoan Indels in Protein-Coding Genes
Belinky, F., Cohen, O., & Huchon, D. (2009) · Molecular Biology and Evolution · doi:10.1093/molbev/msp263 · Cited by 37 · see citing works
Ancient humans and the origin of modern humans
Kelso, J. F., & Prüfer, K. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.09.004 · Cited by 32 · see citing works
Self-citationMale germ cell-specific expression of a novel Patched-domain containing gene Ptchd3
Fan, J., Akabane, H., Zheng, X., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.09.047 · Cited by 31 · see citing works
Ride the wavelet: A multiscale analysis of genomic contexts flanking small insertions and deletionsPreprint
Kvikstad, E. M., Chiaromonte, F., & Makova, K. D. (2009) · Genome Research · doi:10.1101/gr.088922.108 · Cited by 30 · see citing works
Kvikstad, E. M., & Duret, L. (2013) · Molecular Biology and Evolution · doi:10.1093/molbev/mst185 · Cited by 18 · see citing works
Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene
Seno, M. M. G., Kwan, B. Y., Lee-Ng, K. K. M., Moessner, R., Lionel, A. C., Marshall, C. R., & Scherer, S. W. (2011) · BMC Medical Genetics · doi:10.1186/1471-2350-12-45 · Cited by 17 · see citing works
Small Insertions Are More Deleterious than Small Deletions in Human Genomes
Huang, S., Li, J., Xu, A., Huang, G., & You, L. (2013) · Human Mutation · doi:10.1002/humu.22435 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [54]The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature. 2015;526(7571):68–74. PMC4750478 26432245
Cited by
Sorted by citations
A catalog of single nucleotide changes distinguishing modern humans from archaic hominins
Kuhlwilm, M., & Boeckx, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-44877-x · Cited by 108 · see citing works
Something old, something borrowed: admixture and adaptation in human evolution
Dannemann, M., & Racimo, F. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.05.009 · Cited by 87 · see citing works
Self-citationEvolutionary and medical consequences of archaic introgression into modern human genomes
Dolgova, O., & Lao, O. (2018) · Genes · doi:10.3390/genes9070358 · Cited by 34 · see citing works
- Authors
- Chintalapati, M., Dannemann, M., & Prüfer, K.
- Affiliations
- Max Planck Institute for Evolutionary Anthropology (DE)
- Corresponding author
- Prüfer, Kay
- Venue
- BMC Evolutionary Biology
- Published
- 2017-08-04
- Volume
- 17
- Issue
- 1
- Pages
- 179-179
- ISSN
- 1471-2148 (ISSN-L)
- PMC
- PMC5543596
- OpenAlex
- W2743528751
- Cited by
- 13
- References
- 64
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2019: 3 · 2018: 4
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Evolutionary Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- Funders
- Max-Planck-Gesellschaft
- Topics
- Social Sciences › Anthropology › Pleistocene-Era Hominins and Archaeology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- small insertions and deletions, indels, human evolution, intergenic variants, phenotypic diversity
- MeSH terms
- Animals, Gene Frequency, Humans, Phenotype, Phylogeny, Primates, Genome, Evolution, Molecular, Polymorphism, Single Nucleotide, INDEL Mutation, Genome-Wide Association Study, Neanderthals, Gene Ontology
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
