Reconstruction of ancestral protein sequences and its applications

BMC Evolutionary Biology
Wei CaiNick V Grishin

Abstract

Modern-day proteins were selected during long evolutionary history as descendants of ancient life forms. In silico reconstruction of such ancestral protein sequences facilitates our understanding of evolutionary processes, protein classification and biological function. Additionally, reconstructed ancestral protein sequences could serve to fill in sequence space thus aiding remote homology inference. We developed ANCESCON, a package for distance-based phylogenetic inference and reconstruction of ancestral protein sequences that takes into account the observed variation of evolutionary rates between positions that more precisely describes the evolution of protein families. To improve the accuracy of evolutionary distance estimation and ancestral sequence reconstruction, two approaches are proposed to estimate position-specific evolutionary rates. Comparisons show that at large evolutionary distances our method gives more accurate ancestral sequence reconstruction than PAML, PHYLIP and PAUP*. We apply the reconstructed ancestral sequences to homology inference and functional site prediction. We show that the usage of hypothetical ancestors together with the present day sequences improves profile-based sequence similarity searches...Continue Reading

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Methods Mentioned

BETA
nucleotide exchange
amino acid exchange

Software Mentioned

PSI
BIONJ
HMMER
BLAST
BLASTPGP
PAUP
SHUFFLE
ANCESCON
ANSCESCON
PHYLIP

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