Multifaceted Roles of Transposons in Mammalian Evolution and the Future of Transposon Research

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Transposons were once considered ‘junk DNA,’ but recent discoveries emphasize their pivotal role in species’ evolution. Analyzing transposons is essential for understanding the molecular basis of phenotypic diversity within and across species and for uncovering their involvement in various diseases. Transposons inherit characteristics from their origin factors, such as viruses, and accumulate mutations over long evolutionary processes to acquire new functions, thereby contributing to the host’s evolution. Transposons function in various forms, including DNA, RNA and proteins. For example, in their DNA form, they function as transcriptional regulatory sequences. In their RNA form, they bind to receptors that recognize foreign factors like viruses, modulating immune functions. Moreover, by utilizing virus-derived proteins, they provide the host with new features, such as cell fusion. However, the runaway of these functions can lead to various abnormalities, including aging, cancer, mental disorders and autoimmune diseases. In this issue of Genes and Genetic Systems, Mahoko Ueda, Moe Kitazawa and I provide an overview of the functions of transposons in terms of DNA, RNA and proteins. Additionally, Masaki Kawase comprehensively describes the origin, diversity and characteristics of various transposons in mammals. We also introduce new methodologies aimed at elucidating the functions of transposons associated with phenotypic diversity.

Mahoko Ueda has conducted comprehensive identification, database creation and functional analysis of open reading frames derived from ERVs in the mammalian genome. Her work has provided multifaceted insights into the functions of ERVs in mammals. Additionally, she synthesizes key findings from her collaborative work and other seminal studies in the field that shed light on how impaired transposon suppression in dendritic cells can result in excessive immune responses and the development of autoimmune encephalomyelitis. This emphasizes the importance of proper transposon regulation in the context of mammalian immune function. In her review, Ueda provides the latest insights into the molecular mechanisms governing immune function regulation by RNA derived from transposons and its connections to diseases. Moe Kitazawa has conducted functional analyses of virus-derived mammalian genes such as Rtl1. While Rtl1 and other virus-derived genes were initially thought to play a critical role in the evolution of placentas in mammals, Kitazawa and her colleagues have recently revealed that these genes, including Rtl1, also have functions in the brain. This finding suggests that the integration of viral elements into the genomes of ancestral mammals has contributed to diverse evolutionary adaptations in mammals. Kitazawa summarizes the functions of these virus-derived genes in the nervous system and their associations with neurological diseases. The human brain underwent rapid evolution, and it is suggested that this process was influenced by the human-specific amplification of transposons. I and other researchers have recently found that the activation of transposons in a developmental process-specific manner has played a crucial role in the establishment of human-specific genome diversity and transcriptional regulatory networks. I summarize how new transposon insertions after the split between humans and chimpanzees have contributed to human evolution and diversity.

To deepen our understanding of the functions of transposons, it is crucial to expand transposon annotation databases in conjunction with advancements in functional analysis techniques. Transposon databases like RepeatMasker play a vital role in transposon research, with most mammalian studies relying on their annotations. Masaki Kawase compiles information on the phylogenetic relationships, sequence characteristics and genomic distributions of each type of transposon in mice to further enrich the annotation of transposons. This compilation serves as a valuable database for future transposon analyses.

Concluding with a concise look ahead, we expect that ongoing research on transposons will continue to uncover their diverse functions. This evolving field holds the promise of breakthroughs in genetics, biology and disease prevention. We anticipate that this collection of reviews will serve as a valuable resource for researchers and enthusiasts, facilitating their exploration of the multifaceted world of transposons and inspiring new discoveries.