WHO elements – A new category of selfish genetic elements at the borderline between homing elements and transposable elements

• Published in: Seminars in cell & developmental biology 2024-11, Vol.163, p.2-13
• Main Authors: Osborne, Matthieu, Fubara, Athaliah, Ó Cinnéide, Eoin, Coughlan, Aisling Y., Wolfe, Kenneth H.
• Format: Article
• Language: English
• Subjects: DNA Transposable Elements - genetics; Genome evolution; Homing endonucleases; Homing genetic elements; Introns - genetics; LAGLIDADG family endonucleases; Mating-type switching; Mobile genetic elements; Repetitive Sequences, Nucleic Acid - genetics; Yeast
• ISSN: 1084-9521; 1096-3634
• DOI: 10.1016/j.semcdb.2024.04.001

Homing genetic elements are a form of selfish DNA that inserts into a specific target site in the genome and spreads through the population by a process of biased inheritance. Two well-known types of homing element, called inteins and homing introns, were discovered decades ago. In this review we describe WHO elements, a newly discovered type of homing element that constitutes a distinct third category but is rare, having been found only in a few yeast species so far. WHO elements are inferred to spread using the same molecular homing mechanism as inteins and introns: they encode a site-specific endonuclease that cleaves the genome at the target site, making a DNA break that is subsequently repaired by copying the element. For most WHO elements, the target site is in the glycolytic gene FBA1. WHO elements differ from inteins and homing introns in two fundamental ways: they do not interrupt their host gene (FBA1), and they occur in clusters. The clusters were formed by successive integrations of different WHO elements into the FBA1 locus, the result of an ‘arms race’ between the endonuclease and its target site. We also describe one family of WHO elements (WHO10) that is no longer specifically associated with the FBA1 locus and instead appears to have become transposable, inserting at random genomic sites in Torulaspora globosa with up to 26 copies per strain. The WHO family of elements is therefore at the borderline between homing genetic elements and transposable elements.