Abstract
Tandem repeats (TRs) are frequently observed in genomes across all domains of life. Evidence suggests that some TRs are crucial for proteins with fundamental biological functions and can be associated with virulence, resistance, and infectious/neurodegenerative diseases. Genome-scale systematic studies of TRs have the potential to unveil core mechanisms governing TR evolution and TR roles in shaping genomes. However, TR-related studies are often non-trivial due to heterogeneous and sometimes fast evolving TR regions. In this review, we discuss these intricacies and their consequences. We present our recent contributions to computational and statistical approaches for TR significance testing, sequence profile-based TR annotation, TR-aware sequence alignment, phylogenetic analyses of TR unit number and order, and TR benchmarks. Importantly, all these methods explicitly rely on the evolutionary definition of a tandem repeat as a sequence of adjacent repeat units stemming from a common ancestor. The discussed work has a focus on protein TRs, yet is generally applicable to nucleic acid TRs, sharing similar features.
Highlights
Management, Zürich University of Applied Sciences, 8820 Wädenswil, Tandem repeats (TRs) are frequently observed in genomes across all domains of life
Using the evolutionary TR definition, we propose one possible criterion based on the representation of a TR region as a multiple sequence alignment (MSA) of its TR units
Tandem repeats are diverse in their size, type, unit similarity, and distribution across genomes
Summary
A tandem repeat (TR) in genomic sequence is a subsequent recurrence of a single sequence motif. TRs are described by the length of the minimal repeating motif (unit), the number of units, and the similarity among its units. The similarity of initially identical TR units fades with time through point mutations and indels, masking their shared ancestry. Diverged TR units, even when unrecognizable by eye, can maintain structural similarity over long evolutionary times [e.g., Figure 1 in Kajava (2012)]. TRs can mutate by replication slippage (Levinson and Gutman, 1987; Ellegren, 2000), whereby the mispairing of a slipping-strand during the DNA synthesis causes a loss or gain of units as loops of TR units form hairpin structures (Mirkin, 2006).
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