  Proteins encoded by genes containing regions of variable number tandem
repeats (VNTRs) are known to be polymorphic within species but the influence of
their instability in molecular interactions remains unclear. VNTRs are
overrepresented in encoding sequence of particular functional groups where
their presence could influence protein interactions. Using human consensus
coding sequence, this work examines if genomic instability, determined by
regions of VNTRs, influences the number of protein interactions. Findings
reveal that, in relation to protein function, the frequency of unique
interactions in human proteins increase with the number of repeated regions.
This supports experimental evidence that repeat expansion may lead to an
increase in molecular interactions. Genetic diversity, estimated by Ka/Ks,
appeared to decrease as the number of protein-protein interactions increased.
Additionally, G+C and CpG content were negatively correlated with increasing
occurrence of VNTRs. This may indicate that nucleotide composition along with
selective processes can increase genomic stability and thereby restrict the
expansion of repeated regions. Proteins involved in acetylation are associated
with a high number of repeated regions and interactions but a low G+C and CpG
content. While in contrast, less interactive membrane proteins contain a lower
number of repeated regions but higher levels of C+G and CpGs. This work
provides further evidence that VNTRs may provide the genetic variability to
generate unique interactions between proteins.

Genomics