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Bioinformatics Vol. 18 no. 8 2002
Pages 1116-1123
© 2002 Oxford University Press

A branch-and-bound algorithm for the inference of ancestral amino-acid sequences when the replacement rate varies among sites: Application to the evolution of five gene families

Tal Pupko 1,*, Itsik Pe'er 2, Masami Hasegawa 1, Dan Graur 3 and Nir Friedman 4

1 The Institute of Statistical Mathematics, 4-6-7 Minami-Azabu, Minato-ku, Tokyo 106-8569, Japan
2 School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel
3 Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
4 School of Computer Science and Engineering, Hebrew University, Jerusalem 91904, Israel

Received on January 2, 2002 ; revised on March 2, 2002 ; accepted on March 2, 2002

Motivation: We developed an algorithm to reconstruct ancestral sequences, taking into account the rate variation among sites of the protein sequences. Our algorithm maximizes the joint probability of the ancestral sequences, assuming that the rate is gamma distributed among sites. Our algorithm provably finds the global maximum. The use of ‘joint’ reconstruction is motivated by studies that use the sequences at all the internal nodes in a phylogenetic tree, such as, for instance, the inference of patterns of amino-acid replacement, or tracing the biochemical changes that occurred during the evolution of a given protein family.

Results: We give an algorithm that guarantees finding the global maximum. The efficient search method makes our method applicable to datasets with large number sequences. We analyze ancestral sequences of five gene families, exploring the effect of the amount of among-site-rate-variation, and the degree of sequence divergence on the resulting ancestral states.

Availability and supplementary information: http://evolu3.ism.ac.jp/~tal/

Contact: tal{at}ism.ac.jp

* To whom correspondence should be addressed.


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