Variable Tandem Repeats Accelerate Evolution of Coding and Regulatory Sequences

Abstract

Genotype-to-phenotype mapping commonly focuses on two major classes of mutations: single nucleotide polymorphisms (SNPs) and copy number variation (CNV). Here, we discuss an underestimated third class of genotypic variation: changes in microsatellite and minisatellite repeats. Such tandem repeats (TRs) are ubiquitous, unstable genomic elements that have historically been designated as nonfunctional "junk DNA" and are therefore mostly ignored in comparative genomics. However, as many as 10% to 20% of eukaryotic genes and promoters contain an unstable repeat tract. Mutations in these repeats often have fascinating phenotypic consequences. For example, changes in unstable repeats located in or near human genes can lead to neurodegenerative diseases such as Huntington disease. Apart from their role in disease, variable repeats also confer useful phenotypic variability, including cell surface variability, plasticity in skeletal morphology, and tuning of the circadian rhythm. As such, TRs combine characteristics of genetic and epigenetic changes that may facilitate organismal evolvability.

Trichodesmium genome maintains abundant, widespread noncoding DNA in situ, despite oligotrophic lifestyle

“…Because it has also been shown that partial IS sequences can inhibit transposition (78,80), it is possible that these repeats/pseudogenes have not been deleted because they are controlling transposition in the transposase-heavy IMS101. Others have hypothesized that the conserved repeat structures observed in some bacteria could function as recombinationdependent "promoter banks" for adaptation to new conditions, thereby allowing relatively quick "rewiring" of metabolism in subpopulations (59,62,81).…”

E. coli Bacteremia Strains - High diversity and Associations with Agerelated Clinical Phenomena

“…However, VNTRs may be part of inheritance mechanisms and evolution in a much broader perspective than the inheritance of absolutely necessary abilities. Tandem repeats located within gene-coding regions are frequent in the human genome as well as in other organisms studied, and is associated with neurodegenerative diseases [38] and with the imprint of childhood adversities on the genetic risk factors for adult depression [39]. We therefore speculate that VNTRs may be involved in the inheritance of biological vulnerability, thereby justifying this explorative study of host and bacterial determinants of severe infection by MLVA.…”

Principles for the post-GWAS functional characterisation of risk loci

“…Further epigenetic mechanisms that modulate gene expression include miRNAs and miRNA binding sites which can be directly affected by SNPs 32 , and tandem repeats that can impact gene expression e.g. by altering transcription factor binding sites, but also by affecting chromatin structure (reviewed in 33 ).…”