New review from Petar and Omer!
Abstract:
Understanding genomic function has historically relied on sequence conservation across evolutionary time. However, ad-
vances in genomics have revealed that functional innovations often arise from rapidly evolving, nonconserved elements
that are frequently overlooked by conservation-based approaches. Among these, variable number tandem repeats
(VNTRs) act as engines of both functional innovation and phenotypic consequence. VNTRs are repetitive genomic sequences
whose copy numbers can vary significantly between individuals and species, influencing gene regulation, protein structure,
and eventually, phenotypic diversity. Recent long-read assemblies and pangenomes now resolve VNTR loci accurately, enab-
ling robust evolutionary reconstruction and functional associations. Here, we synthesize emerging insights into the functional
and evolutionary impact of VNTRs in mammals. Specifically, we outline pressing questions on the mutational mechanisms
driving VNTR evolution in humans, the selective forces maintaining their structural heterogeneity, and propose a theoretical
framework for their persistence through evolutionary tradeoffs.