ESTIMATION AND RELIABILITY OF MOLECULAR SEQUENCE ALIGNMENTS

The problem of estimating the relatedness of a pair of biological sequ ences is addressed. A stochastic model of sequence evolution is descri bed that allows insertion and deletion as well as replacement of amino acid residues (or substitution of nucleotides) over time. An expectat ion-maximization (EM) algorithm that obtains maximum likelihood estima tes of the model parameters is introduced. The method assumes that the sequences are related by descent from a common ancestor but the align ment (i.e., the precise evolutionary correspondence between residues i n each sequence) is unknown. Results from the E-step of the EM algorit hm are used to assess the likelihood that any two residues are related by direct descent from a common ancestor.