Commentary Classification Problems of Repetitive DNA Sequences Eva Šatovi´ c-Vukši´ c* and Miroslav Plohl   Citation: Šatovi´ c-Vukši´ c, E.; Plohl, M. Classification Problems of Repetitive DNA Sequences. DNA 2021, 1, 84–90. https://doi.org/10.3390/dna1020009 Academic Editor: Darren Griffin Received: 10 August 2021 Accepted: 11 October 2021 Published: 2 November 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Division of Molecular Biology, Ru ¯ der Boškovi´ c Institute, 10000 Zagreb, Croatia; plohl@irb.hr * Correspondence: esatovic@irb.hr Abstract: Repetitive DNA sequences, satellite DNAs (satDNAs) and transposable elements (TEs) are essential components of the genome landscape, with many different roles in genome function and evolution. Despite significant advances in sequencing technologies and bioinformatics tools, detection and classification of repetitive sequences can still be an obstacle to the analysis of genomic repeats. Here, we summarize how specificities in repetitive DNA organizational patterns can lead to an inability to classify (and study) a significant fraction of bivalve mollusk repetitive sequences. We suggest that the main reasons for this inability are: the predominant association of satDNA arrays with Helitron/Helentron TEs; the existence of many complex loci; and the unusual, highly scattered organization of short satDNA arrays or single monomers across the whole genome. The specificities of bivalve genomes confirm the need for introducing diverse organisms as models in order to understand all aspects of repetitive DNA biology. It is expected that further development of sequencing techniques and synergy among different bioinformatics tools and databases will enable quick and unambiguous characterization and classification of repetitive DNA sequences in assembled genomes. Keywords: repetitive DNA classification; satellite DNA; transposable element; Helitron/Helentron; bivalves; genome assemblies 1. Introduction Despite the exponential number of genome sequencing projects arising and spanning all taxa, genomic regions largely composed of repetitive DNA sequences still present substantial technical issues in the assembly of genomes [1]. Repetitive DNAs are mainly constituted of satellite DNAs (satDNAs), formed by sequences repeated in tandem, and of mobile elements, interspersed throughout the genome [2]. According to the estab- lished classical view, satDNAs are associated with constitutive heterochromatin which is commonly located at pericentromeric and subtelomeric chromosomal domains and at interstitial loci of the chromosomal arms. They build long arrays of monomers repeated in tandem, comprised of hundreds to thousands of highly similar repeat units [3]. However, more recent work has introduced new data and showed that satDNA sequences can also be located outside of heterochromatin, where they can be found in different organizational forms: as monomers or monomer fragments, in arrays of diverse length or incorporated into mobile elements, for example [4–10]. In addition, many links show that satDNAs and mobile elements are often tightly interconnected. For example, tandem repeats can be created from mobile elements or their segments, or satDNAs can expand from short internal arrays carried by mobile elements (reviewed in [11]). Sequencing problems arise in attempts to reconstruct repetitive genomic segments, and, subsequently, these regions are still regularly omitted or are misassembled in the available genomic data [12]. Ongoing improvements in sequencing technologies (e.g., long-read PacBio and Nanopore sequencing) are opening the possibility to obtain insights into these missing fractions of assembled genomes [13]. At the same time, a number of programs and software aimed to forward repeat detection and characterization are being generated and/or upgraded (reviewed in [14]), substantially changing our knowledge on DNA 2021, 1, 84–90. https://doi.org/10.3390/dna1020009 https://www.mdpi.com/journal/dna