Exploring the past and the future of protein evolution with ancestral sequence reconstruction: the 'retro' approach to protein engineering

Gumulya, Yosephine and Gillam, Elizabeth M. J. (2016) Exploring the past and the future of protein evolution with ancestral sequence reconstruction: the 'retro' approach to protein engineering. Biochemical Journal, 474 1: 1-19. doi:10.1042/BCJ20160507


Author Gumulya, Yosephine
Gillam, Elizabeth M. J.
Title Exploring the past and the future of protein evolution with ancestral sequence reconstruction: the 'retro' approach to protein engineering
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 1470-8728
0264-6021
Publication date 2016-12-22
Sub-type Article (original research)
DOI 10.1042/BCJ20160507
Open Access Status Not yet assessed
Volume 474
Issue 1
Start page 1
End page 19
Total pages 19
Place of publication London, United Kingdom
Publisher Portland Press
Language eng
Subject 1303 Biochemistry
1312 Molecular Biology
1307 Cell Biology
Abstract A central goal in molecular evolution is to understand the ways in which genes and proteins evolve in response to changing environments. In the absence of intact DNA from fossils, ancestral sequence reconstruction (ASR) can be used to infer the evolutionary precursors of extant proteins. To date, ancestral proteins belonging to eubacteria, archaea, yeast and vertebrates have been inferred that have been hypothesized to date from between several million to over 3 billion years ago. ASR has yielded insights into the early history of life on Earth and the evolution of proteins and macromolecular complexes. Recently, however, ASR has developed from a tool for testing hypotheses about protein evolution to a useful means for designing novel proteins. The strength of this approach lies in the ability to infer ancestral sequences encoding proteins that have desirable properties compared with contemporary forms, particularly thermostability and broad substrate range, making them good starting points for laboratory evolution. Developments in technologies for DNA sequencing and synthesis and computational phylogenetic analysis have led to an escalation in the number of ancient proteins resurrected in the last decade and greatly facilitated the use of ASR in the burgeoning field of synthetic biology. However, the primary challenge of ASR remains in accurately inferring ancestral states, despite the uncertainty arising from evolutionary models, incomplete sequences and limited phylogenetic trees. This review will focus, firstly, on the use of ASR to uncover links between sequence and phenotype and, secondly, on the practical application of ASR in protein engineering.
Keyword Ancestral sequence reconstruction
Directed evolution
Maximum likelihood
Protein engineering
Protein evolution
Thermostabilty
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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