The major component of complex genomes is repetitive elements, which remain recalcitrant to characterization. Using maize as a model system, we analyzed whole genome shotgun (WGS) sequences for the two maize inbred lines B73 and Mo17 using k-mer analysis to quantify the differences between the two genomes. Significant differences were identified in highly repetitive sequences, including centromere, 45S ribosomal DNA (rDNA), knob, and telomere repeats. Genotype specific 45S rDNA sequences were discovered. The B73 and Mo17 polymorphic k-mers were used to examine allelespecific expression of 45S rDNA in the hybrids. Although Mo17 contains higher copy number than B73, equivalent levels of overall 45S rDNA expression indicates that transcriptional or post-transcriptional regulation mechanisms operate for the 45S rDNA in the hybrids. Using WGS sequences of B73xMo17 doubled haploids, genomic locations showing differential repetitive contents were genetically mapped, which displayed different organization of highly repetitive sequences in the two genomes. In an analysis of WGS sequences of HapMap2 lines, including maize wild progenitor, landraces, and improved lines, decreases and increases in abundance of additional sets of k-mers associated with centromere, 45S rDNA, knob, and retrotransposons were found among groups, revealing global evolutionary trends of genomic repeats during maize domestication and improvement.The maize genome (Zea mays ssp. mays) exhibits high levels of genetic diversity among different lines 1-3 . The inbred lines B73 and Mo17 represent two of the most appreciated models for understanding maize genome diversity with respect to small-scale polymorphisms 4-6 and large-scale structural variation 7,8 . In addition, mapping populations of inter-mated B73xMo17 recombinant inbred lines and doubled haploids have been generated to facilitate genetic analyses 9,10 . Numerous comparative genomics studies of other maize cultivars and wild ancestors have examined the origin of maize as well as events of adaptation and artificial selection [11][12][13][14][15][16][17] . However, the studies are limited to comparisons of non-repetitive and low-repetitive sequences.Cytogenetics, genetics, and a few genomics studies have documented variation for many high repetitive sequences among maize lines, which may also contribute to maize evolution and domestication 2,18-20 . In maize, highly repetitive sequences are comprised of several major classes, including ribosome DNA (rDNA), knob repeats, centromere satellite C DNAs (CentC), telomere repeats, and various retrotransposon families. The rDNA repeats consist of two classes, 45S rDNA and 5S rDNA, which are transcribed to ribosomal RNAs (rRNAs). 45S rRNA is further processed into 18S, 5.8S and 26S mature rRNAs, which are then assembled with the 5S rRNA into ribosome subunits 21 . 5S rDNA loci are physically located at the distal of the long arm of chromosome 2 22 , while 45S rDNA tandem arrays are clustered at the nucleolus organizer region (NOR) located at the short a...