Tracking evolution of myoglobin stability in cetaceans using experimentally calibrated computational methods that account for generic protein relaxation

Jeppe Holm, Pouria Dasmeh, Kasper Planeta Kepp

Research output: Contribution to journalJournal articleResearchpeer-review

261 Downloads (Pure)

Abstract

The evolution of cetaceans (whales, dolphins, and porpoises) from land to water is one of the most spectacular events in mammal evolution. It has been suggested that selection for higher myoglobin stability (ΔG of folding) allowed whales to conquer the deep-diving niche. The stability of multi-site protein variants, including ancient proteins, is however hard to describe theoretically. From a compilation of experimental ΔΔG vs. ΔG we first find that protein substitutions are subject to large generic protein relaxation effects. Using this discovery, we develop a simple two-parameter model that predicts multi-site ΔΔG as accurately as standard methods do for single-site mutations and reproduces trends in contemporary myoglobin stabilities. We then apply this new method to the study of the evolution of Mb stability in cetaceans: With both methods the main change in stability (about 1 kcal/mol) occurred very early, and stability was later relaxed in dolphins and porpoises, but was further increased in the sperm whales. This suggests that single proteins can affect whole organism evolution and indicates a role of Mb stability in the evolution of cetaceans. Transition to the deep-diving niche probably occurred already in the ancestor of contemporary baleen and toothed whales. In summary, we have discovered generic stability relaxation effects in proteins that, when incorporated into a simple model, improves the description of multi-site protein variants.
Original languageEnglish
JournalB B A - Proteins and Proteomics
Volume1864
Issue number7
Pages (from-to)825-834
Number of pages10
ISSN1570-9639
DOIs
Publication statusPublished - 2016

Keywords

  • Cetaceans
  • Evolution
  • Myoglobin
  • Protein misfolding
  • Protein stability
  • Whales

Fingerprint

Dive into the research topics of 'Tracking evolution of myoglobin stability in cetaceans using experimentally calibrated computational methods that account for generic protein relaxation'. Together they form a unique fingerprint.

Cite this