HVRs

Hypervariable regions (HVRs) are segments of genetic material or proteins characterized by unusually high sequence variation compared with surrounding regions. The term is used in several biological contexts, reflecting the role of these regions in generating diversity and specificity.

In immunology, hypervariable regions refer to the parts of antibody and T-cell receptor variable domains that determine antigen binding. The antigen-binding surface is formed largely by three hypervariable loops in each chain, known as the complementarity-determining regions (CDR1, CDR2, and CDR3). Diversity arises from somatic recombination of V(D)J gene segments, junctional diversification, and somatic hypermutation, enabling the immune system to recognize a vast array of antigens. The sequence variability of HVRs/CDRs is central to antigen specificity and affinity and is a key consideration in antibody engineering and repertoire studies.

In mitochondrial DNA and other genomes, hypervariable regions are areas with higher mutation rates. In human mtDNA, the most studied HVRs are in the control region, including HVR1 and HVR2, sometimes extended with HVR3. These regions are useful for population genetics, forensic analysis, and studies of maternal lineage because they accumulate mutations more rapidly than coding regions. However, interpretations can be complicated by factors such as heteroplasmy and rate variation across lineages.

HVRs are also leveraged in phylogenetics and comparative genomics as flexible markers for resolving recent evolutionary relationships. Their high variability provides finer resolution than conserved regions but requires careful analysis to account for potential homoplasy and sampling bias.