Ancestral protein reconstruction as a new field in protein engineering

Ayumu Konno, Tomohisa Ogawa, Tsuyoshi Shirai

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Citation (Scopus)


The extent of current research in ancient biology is not restricted by the presence of fossil records, owing to the developments in computational analysis and engineering techniques of proteins. Ancestral sequences of extant genes/proteins can be inferred with the molecular phylogeny reconstruction methods, which are mainly based on maximum-likelihood estimation. Once an ancestral sequence is determined, a reconstruction of the ancestral protein is not difficult by using the current protein engineering techniques, and reproduced protein can be experimentally tested either biochemically or biophysically. To date, such 'experimental molecular archeology' has been examined on several enzymes, elongation factor, photo-reactive proteins, nuclear receptor, and lectin, and largely helped to elucidate evolutionary processes of stability, specificity, and structure of the proteins. Although this method would promise a new field in protein engineering, several problems still remain to be solved, the largest among which should be accuracy of inferred ancestral sequence as a whole. In this chapter, the reported studies of ancestral protein reconstruction are reviewed with a focus on our recent results on the ancestral congerin, which is the ß-galactoside specific lectin of fish involved in the biological defense system. The reconstruction of ancestral congerin is important because two extant isoforms of this protein, congerins I and II, have been rapidly evolving, and their molecular properties and structures have been differentiating due to the natural selection pressures operating on the genes.

Original languageEnglish
Title of host publicationRibosomal Proteins and Protein Engineering
Subtitle of host publicationDesign, Selection and Applications
PublisherNova Science Publishers, Inc.
Number of pages26
ISBN (Print)9781607410058
Publication statusPublished - 2010


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