R2d2 drives selfish sweeps in the house mouse

ANDREW P MORGAN; RACHEL C MCMULLAN; CAROL J BULT; YUNG-HAO CHING; ELISSA J CHESLER; SOFIA I GABRIEL; EVA B GIAGIA-ATHANASOPOULOU; ISLAM GUNDUZ; JEREMY S HERMAN; WESLEY J JOLLEY; LIRAN YADGARY; GEORGE MITSAINAS; LYDIA ORTIZ DE SOLORZANO; M GRAÇA RAMALHINHO; KARL J CAMPBELL; JEREMY B SEARLE; AMANDA J CHUNCO; KAREN L SVENSON; DANIEL W FÖRSTER; JACINT VENTURA; DANIEL M GATTI; GARY A CHURCHILL; MABEL D GIMÉNEZ; ANDREW HOLMES; JAMES M HOLT; ANNA K LINDHOLM; MARIA DA LUZ MATHIAS; JOHN P DIDION; BARBARA REHERMANN; TIMOTHY A BELL; MENG-SHIN SHIAO; JANICE BRITTON-DAVIDIAN; PAT THOMAS- LAEMONT; RICCARDO CASTIGLIA; GEORGE M WEINSTOCK; JAMES J CROWLEY; FERNANDO PARDO-MANUEL DE VILLENA; JOHN E FRENCH; THEODORE GARLAND JR.; SOFIA A GRIZE; HEIDI C HAUFFE; KUNJIE HUA; MARÍA J LÓPEZ-FUSTER; LEONARD MCMILLAN; STEPHAN P ROSSHART; EMANUELA SOLANO; DAVID W THREADGILL; DANIEL POMP

MOLECULAR BIOLOGY AND EVOLUTION

OXFORD UNIV PRESS

Lugar: Oxford; Año: 2016 p. 1381 - 1395

0737-4038

<!-- /* Font Definitions */@font-face{font-family:Cambria;panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Times New Roman";mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Cambria;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}@page Section1{size:612.0pt 792.0pt;margin:72.0pt 90.0pt 72.0pt 90.0pt;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.Section1{page:Section1;}-->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 increasesin frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associatedwith significantly reduced litter sizes in heterozygous mothers, making it atrue 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 incidenceof selfish sweeps, and will elucidate the relative contributions of selfish genes,adaptation and genetic drift to evolution.