R2d2 drives selfish sweeps in the house mouse
John P Didion 1,2,3,*, Andrew P Morgan 1,2,3,*, Liran Yadgary 1,2,3, Timothy A Bell 1,2,3, Rachel C McMullan 1,2,3, Lydia Ortiz de Solorzano 1,2,3, Janice Britton-Davidian 4, Carol J Bult 5, Karl J Campbell 6,7, Riccardo Castiglia 8, Yung-Hao Ching 9, Amanda J Chunco 10, James J Crowley 1, Elissa J Chesler 5, Daniel W Förster 11, John E French 12, Sofia I Gabriel 13, Daniel M Gatti 5, Theodore Garland Jr. 14, Eva B Giagia-Athanasopoulou 15, Mabel D Giménez 16, Sofia A Grize 17, Islam Gündüz 18, Andrew Holmes 19, Heidi C Hauffe 20, Jeremy S Herman 21, James M Holt 22, Kunjie Hua 1, Wesley J Jolley 23, Anna K Lindholm 17, María J López-Fuster 24, George Mitsainas 15, Maria da Luz Mathias 13, Leonard McMillan 22, M Graça Ramalhinho 13, Barbara Rehermann 25, Stephan P Rosshart 25, Jeremy B Searle 26, Meng-Shin Shiao 27, Emanuela Solano 8, Karen L Svenson 5, Pat Thomas-Laemont 10, David W Threadgill 28, Jacint Ventura 29, George M Weinstock 30, Daniel Pomp 1,3, Gary A Churchill 5 and Fernando Pardo-Manuel de Villena 1,2,3
+ Author Affiliations
1. Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, US
2. Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, US
3. Carolina Center for Genome Science, The University of North Carolina at Chapel Hill, Chapel Hill, NC, US
4. Institut des Sciences de l'Evolution, Université de Montpellier, CNRS, IRD, EPHE, Montpellier, FR
5. The Jackson Laboratory, Bar Harbor, ME, US
6. Island Conservation, Puerto Ayora, Galápagos Island, EC
7. School of Geography, Planning & Environmental Management, The University of Queensland, St Lucia, AU
8. Department of Biology and Biotechnologies "Charles Darwin", University of Rome "La Sapienza", Rome, IT
9. Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, TW
10. Department of Environmental Studies, Elon University, Elon, NC, US
11. Department of Evolutionary Genetics, Leibniz-Institute for Zoo and Wildlife Research, Berlin, DE
12. National Toxicology Program, National Institute of Environmental Sciences, NIH, Research Triangle Park, NC, US
13. Department of Animal Biology & CESAM - Centre for Environmental and Marine Studies, Faculty of Sciences, University of Lisbon, Lisboa, PT
14. Department of Biology, University of California Riverside, Riverside, CA, US
15. Section of Animal Biology, Department of Biology, University of Patras, Patras, GR
16. Instituto de Biología Subtropical, CONICET - Universidad Nacional de Misiones, Posadas, MS, AR
17. Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, CH
18. Department of Biology, Faculty of Arts and Sciences, University of Ondokuz Mayis, Samsun, TU
19. Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, US
20. Department of Biodiversity and Molecular Ecology, Research and Innovation Centre, Fondazione Edmund Mach, S. Michele all'Adige, TN, IT
21. Department of Natural Sciences, National Museums Scotland, Edinburgh, UK
22. Department of Computer Science, The University of North Carolina at Chapel Hill, Chapel Hill, NC, US
23. Island Conservation, Santa Cruz, CA, US
24. Faculty of Biology, Universitat de Barcelona, Avinguda Diagonal 643, 08028 Barcelona, ES
25. Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, US
26. Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY, US
27. Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 10400, Bangkok, TH
28. Department of Veterinary Pathobiology and Department of Molecular and Cellular Medicine, Texas A&M University, College Station, TX, US
29. Departament de Biologia Animal, de Biologia Vegetal i d'Ecologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Barcelona, ES
30. Jackson Laboratory for Genomic Medicine, Farmington, CT, US
Corresponding author: Fernando Pardo-Manuel de Villena, fernando@med.unc.edu
Received November 17, 2015. Revision received January 14, 2016. Revision received February 8, 2016. Accepted February 8, 2016.
Abstract
A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation – thereby leaving signatures identical to classical selective sweeps – despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes non-random segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.
© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
FREE PDF GRATIS: Mol Biol Evol
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NOTA DESTE BLOGGER*:
A "lei de segregação", formulada por Gregor Mendel em 1865, sugere que existe uma probabilidade igual de transmissão do alelo materno e paterno.
Mas, a descoberta desafia Darwin: é a primeira vez que os cientistas usaram as populações de ratos, naturais e de laboratório para demonstrar que um “gene egoísta” pode se fixar em uma população de organismos, enquanto que ao mesmo tempo ser prejudicial à "capacidade reprodutiva."
Essa descoberta viola um princípio fundamental em biologia: a teoria da seleção natural de Darwin, que sugere que os alelos benéficos para a capacidade de um organismo sobreviver e reproduzir – sua aptidão - será aumentado continuamente na frequência ao longo do tempo. Enquanto isso, os alelos que são prejudiciais à aptidão irão diminuir na frequência e, eventualmente, desaparecer.
Como que o R2d2 escapa a seleção natural? Enganando na meiose feminina, o tipo especializado de divisão celular que produz os óvulos. A maioria dos animais e plantas, inclusive humanos e ratos, portam dois alelos de cada gene – um alelo de cada pai e mãe. Quando um organismo se reproduz, ele passa adiante somente um alelo para cada descendente.
Pobre Darwin, kaput!!!
* Sobre ombros de gigantes.
* Sobre ombros de gigantes.
