Ancestral Sequence Reconstruction for Exploring Alkaloid Evolution

Research output: Chapter in Book/Report/Conference proceedingChapter


The complex and bioactive monoterpene indole alkaloids (MIAs) found in Catharanthus roseus and related species are the products of many millions of years of evolution through mutation and natural selection. Ancestral sequence reconstruction (ASR) is a method that combines phylogenetic analysis and experimental biochemistry to infer details about past events in protein evolution. Here, I propose that ASR could be leveraged to understand how enzymes catalyzing the formation of complex alkaloids arose over evolutionary time. I discuss the steps of ASR, including sequence selection, multiple sequence alignment, tree inference, and the generation and characterization of inferred ancestral enzymes.

Original languageEnglish
Title of host publicationCatharanthus roseus
Subtitle of host publicationMethods and Protocols
Number of pages15
ISBN (Electronic)978-1-0716-2349-7
ISBN (Print)978-1-0716-2348-0
Publication statusPublished - 23 Jun 2022

Publication series

NameMethods in molecular biology
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Bibliographical note

Publisher Copyright:
© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.


  • Enzyme evolution
  • Metabolic evolution
  • Molecular evolution
  • Phylogenetics
  • Specialized metabolism

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