Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection
Open accessAbstract
The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.
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Signals of selection associated with serotonergic signaling have been identified in a tame strain of rat and the domesticated goat.
“Signals of selection associated with serotonergic signaling have also been identified in a tame strain of rat and the domesticated goat (Albert et al., 2011;Dong et al., 2015).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Albert et al., 2011
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Cites
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · see citing works
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
Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.
Tajima, F. (1989) · Genetics · doi:10.1093/genetics/123.3.585 · Cited by 13,991 · see citing works
(1982) · Trends in Neurosciences · doi:10.1016/0166-2236(82)90076-5 · Cited by 9,148 · see citing works
A map of human genome variation from population-scale sequencing.
The 1000 Genomes Project Consortium (2010) · Nature · doi:10.1038/nature09534 · Cited by 7,877 · see citing works
The hitch-hiking effect of a favourable gene
Smith, J. M., & Haigh, J. (1974) · Genetical Research · doi:10.1017/s0016672300014634 · Cited by 3,415 · see citing works
The hitch-hiking effect of a favourable gene
MAYNARD, J., & Haigh, J. (2007) · Genetics Research · doi:10.1017/s0016672308009579 · Cited by 2,663 · see citing works
Generating samples under a Wright–Fisher neutral model of genetic variation
Hudson, R. R. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.2.337 · Cited by 2,397 · see citing works
Targeted capture and massively parallel sequencing of 12 human exomes
Ng, S. B., Turner, E. H., Robertson, P. D., Flygare, S. D., Bigham, A. W., Lee, C., Shaffer, T., Wong, M., Bhattacharjee, A., Eichler, E. E., et al. (2009) · Nature · doi:10.1038/nature08250 · Cited by 2,030 · see citing works
Self-citationExome sequencing identifies the cause of a mendelian disorder
Ng, S. B., Buckingham, K. J., Lee, C., Bigham, A. W., Tabor, H. K., Dent, K. M., Huff, C. D., Shannon, P. T., Jabs, E. W., Nickerson, D. A., et al. (2010) · Nature Genetics · doi:10.1038/ng.499 · Cited by 1,957 · see citing works
Gutenkunst, R. N., Hernandez, R. D., Williamson, S. H., & Bustamante, C. D. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000695 · Cited by 1,906 · cited 2× · see citing works
“However, using the likelihood based approach dadi (Gutenkunst et al., 2009), we estimated a very severe reduction in effective population size (to 0.”
MethodHitchhiking Under Positive Darwinian Selection
Fay, J. C., & Wu, C.-I. (2000) · Genetics · doi:10.1093/genetics/155.3.1405 · Cited by 1,819 · see citing works
The genetics of quantitative traits: challenges and prospects
Mackay, T. F. C., Stone, E. A., & Ayroles, J. F. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2612 · Cited by 1,292 · see citing works
Aggressive Behavior and Altered Amounts of Brain Serotonin and Norepinephrine in Mice Lacking MAOA
Cases, O., Seif, I., Grimsby, J. S., Gaspar, P., Chen, K., Vandormael‐Pournin, S., Müller, U., Aguet, M., Babinet, C., Shih, J. C., et al. (1995) · Science · doi:10.1126/science.7792602 · Cited by 1,225 · see citing works
Kandel, E. R., Koester, J. D., Mack, S. H., & Siegelbaum, S. A. (1985) · Cited by 1,180 · see citing works
Whole-genome resequencing reveals loci under selection during chicken domestication
Rubin, C.-J., Zody, M. C., Eriksson, J., Meadows, J. R. S., Sherwood, E., Webster, M. T., Jiang, L., Ingman, M., Sharpe, T., Ka, S., et al. (2010) · Nature · doi:10.1038/nature08832 · Cited by 1,138 · see citing works
Self-citationGenomic scans for selective sweeps using SNP dataPreprint
Nielsen, R., Williamson, S., Kim, Y., Hubisz, M. J., Clark, A. G., & Bustamante, C. D. (2005) · Genome Research · doi:10.1101/gr.4252305 · Cited by 1,024 · see citing works
Hermisson (2005) · doi:10.1534/genetics.104.036947 · Cited by 1,009 · see citing works
A unique central tryptophan hydroxylase isoform
Walther, D. J., & Bäder, M. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00556-2 · Cited by 752 · see citing works
Ezdon, C. (1987) · American Journal of Occupational Therapy · doi:10.5014/ajot.41.1.59b · Cited by 729 · see citing works
Hubbard, T., Aken, B. L., Ayling, S., Ballester, B., Beal, K. M., Bragin, E., Brent, S., Chen, Y., Clapham, P., Clarke, L., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn828 · Cited by 671 · see citing works
Molecular detection of pheromone signals in mammals: from genes to behaviour
Dulac, C. G., & Torello, A. T. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1140 · Cited by 662 · see citing works
Detecting a Local Signature of Genetic Hitchhiking Along a Recombining Chromosome
Kim, Y., & Stephan, W. (2002) · Genetics · doi:10.1093/genetics/160.2.765 · Cited by 639 · see citing works
Evaluation of next generation sequencing platforms for population targeted sequencing studies
Harismendy, O., Ng, P. C., Strausberg, R. L., Wang, X., Stockwell, T. B., Beeson, K. Y., Schork, N. J., Murray, S. S., Topol, E. J., Levy, S., et al. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r32 · Cited by 614 · see citing works
Advanced intercross lines, an experimental population for fine genetic mapping.
Darvasi, A., & Soller, M. (1995) · Genetics · doi:10.1093/genetics/141.3.1199 · Cited by 579 · see citing works
Strategies for mapping and cloning quantitative trait genes in rodents
Jonathan Flint, C., Valdar, W. S. J., Shifman, S., & Mott, R. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1576 · Cited by 497 · see citing works
Genome-wide analysis of a long-term evolution experiment with Drosophila
Burke, M. K., Dunham, J. P., Shahrestani, P., Thornton, K. R., Rose, M. R., & Long, A. D. (2010) · Nature · doi:10.1038/nature09352 · Cited by 448 · see citing works
Adaptation–not by sweeps alone
Pritchard, J. K., & Di Rienzo, A. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2880 · Cited by 445 · see citing works
THE SIGNATURE OF POSITIVE SELECTION ON STANDING GENETIC VARIATION
Przeworski, M., Coop, G., & Wall, J. D. (2005) · Evolution · doi:10.1554/05-273.1 · Cited by 435 · see citing works
Theoretical and empirical issues for marker-assisted breeding of congenic mouse strains
Markel, P. D., Shu, P., Ebeling, C., Carlson, G. A., Nagle, D. L., Smutko, J. S., & Moore, K. J. (1997) · Nature Genetics · doi:10.1038/ng1197-280 · Cited by 401 · see citing works
Fast and flexible simulation of DNA sequence dataPreprint
Chen, G. K., Marjoram, P., & Wall, J. D. (2008) · Genome Research · doi:10.1101/gr.083634.108 · Cited by 394 · see citing works
Powell, E. M., Campbell, D. B., Stanwood, G. D., Davis, C., Noebels, J. L., & Levitt, P. R. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-02-00622.2003 · Cited by 333 · see citing works
Soft Sweeps II—Molecular Population Genetics of Adaptation from Recurrent Mutation or Migration
Pennings, P. S., & Hermisson, J. (2006) · Molecular Biology and Evolution · doi:10.1093/molbev/msj117 · Cited by 329 · see citing works
libsequence: a C++ class library for evolutionary genetic analysis
Thornton, K. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg316 · Cited by 329 · see citing works
Li, Y., Vinckenbosch, N., Tian, G., Huerta‐Sánchez, E., Jiang, T., Jiang, H., Albrechtsen, A., Andersen, G., Cao, H., Korneliussen, T. S., et al. (2010) · Nature Genetics · doi:10.1038/ng.680 · Cited by 307 · see citing works
Improved base calling for the Illumina Genome Analyzer using machine learning strategies
Kircher, M., Stenzel, U., & Kelso, J. F. (2009) · Genome biology · doi:10.1186/gb-2009-10-8-r83 · Cited by 271 · see citing works
Alta-Cyclic: a self-optimizing base caller for next-generation sequencing
Erlich, Y., Mitra, P. P., delaBastide, M., McCombie, W. R., & Hannon, G. J. (2008) · Nature Methods · doi:10.1038/nmeth.1230 · Cited by 216 · see citing works
Self-citationA flexible forward simulator for populations subject to selection and demography
Hernandez, R. D. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn522 · Cited by 208 · 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
Self-citationThe Hitchhiking Effect on Linkage Disequilibrium Between Linked Neutral Loci
Stephan, W., Song, Y. S., & Langley, C. H. (2006) · Genetics · doi:10.1534/genetics.105.050179 · Cited by 162 · see citing works
Genomic drift and copy number variation of sensory receptor genes in humans
Nozawa, M., Kawahara, Y., & Nei, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709956104 · Cited by 157 · see citing works
Albert, F. W., Shchepina, O., Winter, C., Römpler, H., Teupser, D., Palme, R., Ceglarek, U., Kratzsch, J., Sohr, R., Trut, L. N., et al. (2007) · Hormones and Behavior · doi:10.1016/j.yhbeh.2007.11.010 · Cited by 157 · see citing works
Self-citationProgress and prospects in mapping recent selection in the genome
Thornton, K., Jensen, J. D., Becquet, C., & Andolfatto, P. (2007) · Heredity · doi:10.1038/sj.hdy.6800967 · Cited by 136 · see citing works
Self-citationGenetic architecture of tameness in a rat model of animal domestication
Albert, F. W., Carlborg, O., Plyusnina, I., Besnier, F., Hedwig, D., Lautenschläger, S., Lorenz, D., McIntosh, J., Neumann, C., Richter, H., et al. (2009) · Genetics · doi:10.1534/genetics.109.102186 · Cited by 136 · see citing works
Self-citationThe Rat Genome Database, update 2007--Easing the path from disease to data and back again
Twigger, S. N., Shimoyama, M. E., Bromberg, S. K., Kwitek, A. E., Jacob, H. J., & the RGD Team (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl988 · Cited by 132 · see citing works
Naumenko, E. V., Popova, N. K., Nikulina, E. M., Dygalo, N. N., Shishkina, G. T., Borodin, P. M., & Markel, A. L. (1989) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(89)90434-6 · Cited by 127 · see citing works
Mutations in human monoamine-related neurotransmitter pathway genes
Haavik, J., Blau, N., & Thöny, B. (2008) · Human Mutation · doi:10.1002/humu.20700 · Cited by 104 · see citing works
PLYUSNINA, I., & OSKINA, I. (1997) · Physiology & Behavior · doi:10.1016/s0031-9384(96)00445-3 · Cited by 98 · see citing works
Self-citationMice Lacking PKCγ Exhibit Decreased Anxiety
Bowers, B. J., Collins, A. C., Tritto, T., & Wehner, J. M. (2000) · Behavior Genetics · doi:10.1023/a:1001951104208 · Cited by 61 · see citing works
Drögemüller, C., Tetens, J., Sigurðsson, S., Gentile, A., Testoni, S., Lindblad‐Toh, K., & Leeb, T. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1001079 · Cited by 53 · see citing works
The GABA type A receptor α5 subunit gene is associated with bipolar I disorder
Otani, K., Ujike, H., Tanaka, Y., Morita, Y., Katsu, T., Nomura, A., Uchida, N., Hamamura, T., Fujiwara, Y., & Kuroda, S. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.02.010 · Cited by 43 · see citing works
Rönnegård, L., Besnier, F., & Carlborg, Ö. (2008) · Genetics · doi:10.1534/genetics.107.083162 · Cited by 33 · see citing works
Self-citation
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Wilkins, A. S., Wrangham, R. W., & Fitch, W. T. (2014) · Genetics · doi:10.1534/genetics.114.165423 · Cited by 751 · see citing works
A comparison of brain gene expression levels in domesticated and wild animals
Albert, F. W., Somel, M., Carneiro, M., Aximu-Petri, A., Halbwax, M., Thalmann, O., Blanco-Aguiar, J. A., Plyusnina, I. Z., Trut, L., Villafuerte, R., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002962 · Cited by 154 · see citing works
Self-citationThe Domestication Makeup: Evolution, Survival, and Challenges
Ahmad, H. I., Ahmad, M. J., Jabbir, F., Ahmar, S., Ahmad, N., Elokil, A. A., & Chen, J. (2020) · Frontiers in Ecology and Evolution · doi:10.3389/fevo.2020.00103 · Cited by 98 · see citing works
Li, M., Tian, S., Yeung, C. K. L., Meng, X., Tang, Q., Niu, L., Wang, X., Jin, L., Ma, J., Long, K., et al. (2014) · Scientific Reports · doi:10.1038/srep04678 · Cited by 87 · see citing works
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Heyne, H. O., Lautenschläger, S., Nelson, R., Besnier, F., Rotival, M., Cagan, A., Kozhemyakina, R., Plyusnina, I. Z., Trut, L., Carlborg, Ö., et al. (2014) · Genetics · doi:10.1534/genetics.114.168948 · Cited by 72 · see citing works
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Johnson, J. L., Wittgenstein, H., Mitchell, S. E., Hyma, K. E., Temnykh, S. V., Kharlamova, A. V., Gulevich, R. G., Vladimirova, A. V., Fong, H. W. F., Acland, G. M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0127013 · Cited by 38 · see citing works
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- Authors
- Albert, F. W., Hodges, E., Jensen, J. D., Besnier, F., Xuan, Z., Rooks, M., Bhattacharjee, A., Brizuela, L., Good, J. M., Green, R. E., Burbano, H. A., Plyusnina, I. Z., Trut, L., Andersson, L., Schöneberg, T., Carlborg, Ö., Hannon, G. J., & Pääbo, S.
- Affiliations
- Princeton University (US)
- Cold Spring Harbor Laboratory (US)
- University of Massachusetts Chan Medical School (US)
- Norwegian Institute of Marine Research (NO)
- The University of Texas at Dallas (US)
- Agilent Technologies (United States) (US)
- Max Planck Institute for Evolutionary Anthropology (DE)
- University of California, Santa Cruz (US)
- Institute of Cytology and Genetics (RU)
- Uppsala University (SE)
- Leipzig University (DE)
- Swedish University of Agricultural Sciences (SE)
- Corresponding author
- Albert, F W
- ORCID
- Venue
- Heredity
- Published
- 2011-02-09
- Volume
- 107
- Issue
- 3
- Pages
- 205-214
- ISSN
- 0018-067X (ISSN-L)
- 1365-2540
- PMC
- PMC3183948
- OpenAlex
- W2123232355
- Cited by
- 28
- References
- 52
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 5
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Heredity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Stiftelsen för Strategisk Forskning
- Svenska Forskningsrådet Formas
- Max-Planck-Gesellschaft
- Vetenskapsrådet
- National Institutes of Health (CA013106)
- National Cancer Institute (P01CA013106)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
- Keywords
- tameness, aggression, quantitative trait loci, positive selection, polygenic selection, Rattus norvegicus, genetic variants, haplotype diversity, behavioral genetics
- MeSH terms
- Aggression, Alleles, Animals, Base Sequence, Female, Male, Phenotype, Selection, Genetic, Genetic Variation, Genome, Sequence Analysis, DNA, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Rats, High-Throughput Nucleotide Sequencing
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