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Nucleic Acids Research, 1992, Vol. 20, No. 10 2511-2516
© 1992

MOLECULAR BIOLOGY

Multiple alignment using simulated annealing: branch point definition in human mRNA splicing

Alexander V. Lukashin+, Jacob Engelbrecht and Søren Brunak*

Department of Physical Chemistry and Computational Neural Network Center (CONNECT), The Technical University of Denmark DK-2800 Lyngby, Denmark

* To whom correspondence should be addressed

Received January 28, 1992. Revised March 31, 1992. Accepted March 31, 1992.

A method for the simultaneous alignment of a very large number of sequences using simulated annealing is presented. The total running time of the algorithm does not depend explicitly on the number of sequences treated. The method has been used for the simultaneous alignment of 1462 human intron sequences upstream of the intron-exon boundary. The consensus sequence of the aligned set together with a calculation of the Shannon information clearly shows that several sequence motives are conserved: (i) a previously undetected guanosine rich region, (ii) the branch point and (iii) the polypyrimidine tract. The nucleotide frequencies at each position of the branch point consensus sequence qualitatively reproduce the frequencies of the experimentally determined branch points.

+Permanent address: Institute of Molecular Genetics, USSR Academy of Sciences, Moscow, 123182, Russia


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