Functional Mechanisms of Microsatellite DNA in Eukaryotic Genomes

Abstract

Microsatellite repeat DNA is best known for its length mutability, which is implicated in several neurological diseases and cancers, and often exploited as a genetic marker. Less well-known is the body of work exploring the widespread and surprisingly diverse functional roles of microsatellites. Recently, emerging evidence includes the finding that normal microsatellite polymorphism contributes substantially to the heritability of human gene expression on a genome-wide scale, calling attention to the task of elucidating the mechanisms involved. At present, these are underexplored, but several themes have emerged. I review evidence demonstrating roles for microsatellites in modulation of transcription factor binding, spacing between promoter elements, enhancers, cytosine methylation, alternative splicing, mRNA stability, selection of transcription start and termination sites, unusual structural conformations, nucleosome positioning and modification, higher order chromatin structure, noncoding RNA, and meiotic recombination hot spots.

Genomic landscape of oxidative DNA damage and repair reveals regioselective protection from mutagenesis

“…Interestingly, specific sequences display preferential damage enrichment in the OGG1-enriched samples, such as (CCCA) n and (ATGGTG) n . Micro-satellites are capable of forming non-B-DNA structures, such as hairpins 48 ; we suggest that changes in the DNA's local structural properties impairs 8OxoG-processing on these genomic features with possible regulatory functionality.…”

Fast sequence-based microsatellite genotyping development workflow

“…The ability of SSRseq to characterize SNP and indel present along the sequences, in addition to the targeted microsatellite, represents a new opportunity to produce empirical data to apply existing theoretical and statistical frameworks that integrate linked polymorphism with different mutation characteristics (Payseur and Cutter 2006). Finally, the ease and cost effectiveness of parallel development for multiple species make these approach convenient to develop powerful multilocus datasets for comparative population and community genetics studies (Crutsinger 2016), and to further investigate the functional implications (Bagshaw 2017) and adaptive potential of microsatellite variation among natural populations (Xie et al 2019).…”

“…Secondly, variation in the number of repeated oligonucleotide motif is a unique kind of polymorphism with specific mutation mechanism and rate which in itself provides a complementary picture of genetic variation to nucleotide substitutions across populations (Haasl and Payseur 2011) and genomes (Willems et al 2014). Thirdly, it becomes more and more obvious that microsatellite polymorphism is involved in numerous biological processes such as gene expression regulation and epigenetic mechanisms (Bagshaw 2017;Sadd et al 2018), and more generally in phenotypic variation (Xie et al 2019) including human diseases (Gymrek 2017;Hannan 2018). Thus, while marker preference evolves through time with specific markers dominating the genotyping field over a period of time following technological advances (Schlötterer 2004;Seeb et al 2011), maintaining our capability to interrogate any kind of polymorphism in the context of rapid HTS technological advances is paramount and should be prioritized.…”

A DNA G-quadruplex/i-motif hybrid

“…Repetitive DNA makes up more than 50% of the human genome, 67 with microsatellite (1-10 nt), minisatellite (10 to several hundred nt), and macrosatellite (up to thousands of nt) repeats, making up ~3%. 68 Satellite DNA is involved in a variety of biological functions and pathologies, 69 and repeat sequences have been implicated as drivers of evolution through the formation of noncanonical structures that result in genomic instability. 70 Though there are now some examples for how repetitive DNA can impact biological function, the structural basis for this is largely unknown.…”