The Telomere Paradox: Stable Genome Preservation with Rapidly Evolving Proteins

Trends Genet. 2020 Apr;36(4):232-242. doi: 10.1016/j.tig.2020.01.007. Epub 2020 Feb 12.


Telomeres ensure chromosome length homeostasis and protection from catastrophic end-to-end chromosome fusions. All eukaryotes require this essential, strictly conserved telomere-dependent genome preservation. However, recent evolutionary analyses of mammals, plants, and flies report pervasive rapid evolution of telomere proteins. The causes of this paradoxical observation - that unconserved machinery underlies an essential, conserved function - remain enigmatic. Indeed, these fast-evolving telomere proteins bind, extend, and protect telomeric DNA, which itself evolves slowly in most systems. We hypothesize that the universally fast-evolving subtelomere - the telomere-adjacent, repetitive sequence - is a primary driver of the 'telomere paradox'. Under this model, radical sequence changes in the subtelomere perturb subtelomere-dependent, telomere functions. Compromised telomere function then spurs adaptation of telomere proteins to maintain telomere length homeostasis and protection. We propose an experimental framework that leverages both protein divergence and subtelomeric sequence divergence to test the hypothesis that subtelomere sequence evolution shapes recurrent innovation of telomere machinery.

Keywords: paradox; positive selection; rapid evolution; selfish genetic elements; subtelomere; telomere.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Diptera / genetics
  • Evolution, Molecular*
  • Humans
  • Plants / genetics
  • Repetitive Sequences, Nucleic Acid / genetics
  • Telomere / genetics*
  • Telomere Homeostasis / genetics*
  • Telomere-Binding Proteins / genetics*


  • Telomere-Binding Proteins