From Junk DNA to Genomic Treasure: Impacts of Transposable Element DNA, RNA, and Protein in Mammalian Development and Disease.

Transposable elements (TEs) have hijacked cellular machineries to replicate and spread throughout host genomes. TEs now make up a significant portion of eukaryotic genomes and play notable roles in genomic evolution, driving both speciation and providing raw material for genetic innovation. Barbara McClintock's pioneering work on these "jumping genes" laid the foundation for modern TE research; however, her paradigm-shifting theories in which TEs act as "controlling elements" were initially rejected due to the long-held belief that TEs were "junk" or parasitic DNA elements. Historically, the highly repetitive nature of TEs made it challenging to both identify and investigate functions. However, recent advances in genomics have greatly accelerated our understanding of TEs. Despite their potential to cause insertional mutagenesis and disease, many transposable elements have been co-opted by host genomes to contribute to gene regulation and development. In contrast to protein-coding genes that typically begin their journey as DNA, are transcribed into RNA, and reach their ultimate functional form as proteins, TEs can function as cis-regulatory DNA, functional RNA, and in rare cases, domesticated proteins and fusion events between TE and host genes. Driven by rapidly advancing technologies, the roles of TEs in both development and disease are being uncovered faster than ever, making current and future work an exciting continuation of Barbara McClintock's groundbreaking legacy.