Prediction of the exon-intron structure by comparison of genomic sequences

Abstract

An algorithm for prediction of the exon-intron structure of higher eukaryotic genes is suggested. The algorithm is based on comparison of genomic sequences of homologous genes from different species. It uses the fact that protein-coding sequences evolve slower than noncoding regions. Unlike the existing comparison methods, the proposed algorithm, which is a modified version of splicing alignment, compares not nucleotide but amino acid sequences, which increases its sensitivity. Conservation of the exon-intron structures of the compared genes is not assumed. The algorithm is implemented in the program Pro-Gen. The testing of the algorithm demonstrated that it can be successfully applied to prediction of vertebrate genes, and in some cases, for more distant comparisons (e.g., vertebrates and insects or nematodes). Thus, the program can be used for prediction of human genes by comparison with genes of model organisms: mouse, fugu, drosophila, and nematode. The algorithm overcomes deficiencies of the existing methods, both statistical (insufficient reliability) and similarity-based (inapplicability to completely new genes).