Protein function influences frequency of encoded regions containing VNTRs and number of unique interactions

TL;DR

This study investigates how variable number tandem repeats (VNTRs) in protein-coding genes influence protein interactions and genomic stability, revealing correlations between VNTR frequency, protein function, and nucleotide composition.

Contribution

It demonstrates that VNTR regions affect the number of protein interactions and are linked to nucleotide composition and genomic stability, advancing understanding of protein variability.

Findings

Protein interaction frequency increases with VNTR regions.

Genetic diversity decreases as protein interactions increase.

G+C and CpG content negatively correlate with VNTR occurrence.

Abstract

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.