Abstract
BackgroundThe ubiquitous presence of short tandem repeats (STRs) in virtually all genomes implicates their functional relevance, while a widely-accepted definition of STR is yet to be established. Previous studies majorly focus on relatively longer STRs, while shorter repeats were generally excluded. Herein, we have adopted a more generous criteria to define shorter repeats, which has led to the definition of a much larger number of STRs that lack prior analysis. Using this definition, we analyzed the short repeats in 55 randomly selected segments in 55 randomly selected genomic sequences from a fairly wide range of species covering animals, plants, fungi, protozoa, bacteria, archaea and viruses.ResultsOur analysis reveals a high percentage of short repeats in all 55 randomly selected segments, indicating that the universal presence of high-content short repeats could be a common characteristic of genomes across all biological kingdoms. Therefore, it is reasonable to assume a mechanism for continuous production of repeats that can make the replicating process relatively semi-conservative. We have proposed a folded replication slippage model that considers the geometric space of nucleotides and hydrogen bond stability to explain the mechanism more explicitly, with improving the existing straight-line slippage model. The folded slippage model can explain the expansion and contraction of mono- to hexa- nucleotide repeats with proper folding angles. Analysis of external forces in the folding template strands also suggests that expansion exists more commonly than contraction in the short tandem repeats.ConclusionThe folded replication slippage model provides a reasonable explanation for the continuous occurrences of simple sequence repeats in genomes. This model also contributes to the explanation of STR-to-genome evolution and is an alternative model that complements semi-conservative replication.
Highlights
The ubiquitous presence of short tandem repeats (STRs) in virtually all genomes implicates their functional relevance, while a widely-accepted definition of Short tandem repeat (STR) is yet to be established
It is widely accepted that DNA slippage is thought to be the primary mechanism for driving STR expansion or contraction, slippage involves DNA polymerase pausing, dissociation and re-association [5, 32, 33], which may help to understand the expansion and contraction of long repeat sequences; it seems difficult to explain the remain of high percentage of short repeat sequences, and it is necessary to improve the slippage model more explicit to explain the generation of large amounts of short repeat sequences [34,35,36,37]
We calculated the bent replicating DNA molecule with strictly considering the geometric space, the relationship between the phosphodiester bond and hydrogen bond, and the stability of paired nucleotides; and proposed a folded replication slippage model for explaining repeats occurrence, which seems more reasonable to explain the remaining of high percentage short repeats in genomes, and to explain the frequent STR expansion and contraction
Summary
The ubiquitous presence of short tandem repeats (STRs) in virtually all genomes implicates their functional relevance, while a widely-accepted definition of STR is yet to be established. We have adopted a more generous criteria to define shorter repeats, which has led to the definition of a much larger number of STRs that lack prior analysis. Using this definition, we analyzed the short repeats in 55 randomly selected segments in 55 randomly selected genomic sequences from a fairly wide range of species covering animals, plants, fungi, protozoa, bacteria, archaea and viruses. This work may put forward some constructive suggestions for complementing the theory of semi-conservative replication
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