Mechanisms and impacts of genomic changes that are mediated by repetitive sequences in eukaryotes

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The genome contains all the information an organism requires to function. Therefore, organisms have evolved mechanisms to stably maintain the genome, for example, by faithfully duplicating the genome and repairing DNA damage with high accuracy. When these mechanisms are compromised, genomes become destabilized and undergo various kinds of changes. These changes include changes in the nucleotide sequence. Genomes can also undergo large-scale changes that induce deletion, duplications, inversions, insertions and translocations.

Genomic changes can compromise genome stability and cellular integrity, are causes of cancers and numerous other diseases, and accelerate aging. However, some genomic changes contribute to phenotypic variation and play a key role in adaptation, speciation and evolution. Genomic changes can thus have both positive and negative impacts on organisms, emphasizing the importance in understanding what triggers these genomic changes and how they are mediated at the molecular level. Eukaryotic genomes are replete with different kinds of repeated sequences. In the post-genomic era, mounting evidence indicates that repetitive sequences are responsible for the majority of chromosomal structural variation.

In this issue, we cover genomic changes mediated by three different repetitive sequences in eukaryotic genomes. First, Ahmad Luqman-Fatah and Tomoichiro Miyoshi introduce long interspersed element-1 (LINE-1 or L1), which are transposable elements that are dispersed throughout the genome and occupy nearly half of the human genome. They overview mechanisms and impacts of L1-mediated retrotransposition. Moreover, they discuss not only defense mechanisms that hosts have evolved to restrict L1 retrotransposition but also some host factors that facilitate L1 retrotransposition. Second, Junko Kanoh overviews subtelomeres that are adjacent to telomeres at chromosome ends. Unlike telomeres, subtelomeres occupy a much larger region (~100 kb in the case of subtelomeres of Schizosaccharomyces pombe) and contain multiple types of segments that are homologous among subtelomeres of each species. She summarizes recent discoveries that uncover highly variable and mosaic structures of subtelomeres and discusses how subtelomeres have evolved. Finally, I overview the ribosomal RNA gene (rDNA) locus in budding yeast, which contains a tandem array of ~150 rDNA copies. rDNA copy number is normally stably maintained but changes in rDNA copy number are favored in certain situations. I discuss how cells regulate rDNA stability, especially focusing on the pathway choice made during repair of DNA double-strand breaks that are formed in response to programmed DNA replication fork arrest.

These reviews cover recent advancements of our understanding of the mechanisms behind genomic changes mediated by repetitive sequences in eukaryotic genomes. Furthermore, their authors discuss how these changes impact cellular and organismal functions. We also leave readers with important but still unanswered questions that need to be addressed in future studies.