Functional centromeres, the chromosomal sites of spindle attachment during cell division, are marked epigenetically by the centromerespecific histone H3 variant cenH3 and typically contain long stretches of centromere-specific tandem DNA repeats (âź1.8 Mb in maize). In 23 inbreds of domesticated maize chosen to represent the genetic diversity of maize germplasm, partial or nearly complete loss of the tandem DNA repeat CentC precedes 57 independent cenH3 relocation events that result in neocentromere formation. Chromosomal regions with newly acquired cenH3 are colonized by the centromere-specific retrotransposon CR2 at a rate that would result in centromere-sized CR2 clusters in 20,000-95,000 y. Three lines of evidence indicate that CentC loss is linked to inbreeding, including (i) CEN10 of temperate lineages, presumed to have experienced a genetic bottleneck, contain less CentC than their tropical relatives; (ii) strong selection for centromere-linked genes in domesticated maize reduced diversity at seven of the ten maize centromeres to only one or two postdomestication haplotypes; and (iii) the centromere with the largest number of haplotypes in domesticated maize (CEN7) has the highest CentC levels in nearly all domesticated lines. Rare recombinations introduced one (CEN2) or more (CEN5) alternate CEN haplotypes while retaining a single haplotype at domestication loci linked to these centromeres. Taken together, this evidence strongly suggests that inbreeding, favored by postdomestication selection for centromere-linked genes affecting key domestication or agricultural traits, drives replacement of the tandem centromere repeats in maize and other crop plants. Similar forces may act during speciation in natural systems.centromere drive | centromere paradox | founder effect | hemicentric inversion | linkage disequilibrium C entromere-specific tandemly arranged DNA repeats vary in length and nucleotide sequence between species. The puzzling observation that centromeres can consist of highly variable sequences despite being involved in an essential cellular function (i.e., chromosome segregation) has been coined the "centromere paradox" (1). "Centromere drive" has been proposed to preferentially segregate the "favored" centromere into the female gamete and thereby provide the selective force that acts on centromere DNA sequences and interacting proteins (2).Maize (Zea mays ssp. mays) was domesticated between 7.5 and 10 thousand years ago (ka) from wind-pollinated outcrossing wild teosinte (Z. mays ssp. parviglumis) (3, 4) in a process that dramatically changed its morphology. Several quantitative trait loci (QTLs) responsible for these morphological changes were identified in pioneering work (5-8), and a large number of additional genetic loci involved in maize domestication and improvement were subsequently identified in genome-wide scans (9). Gene (and centromere) flow between the fully interfertile maize and teosinte subspecies has been documented (10, 11). Functional centromeres of maize consist of 1-2 Mb of DN...