The problem of identifying genes in genomic DNA sequences by computational methods has attracted considerable research attention in recent years. From one point of view, the problem is closely

INTRODUCTION Almost all the nuclear genes coding for proteins in eukaryotes are split into exon and intron sequences. Thus questions such as `what makes an exon an exon?' and `how is an exon recognized by the gene expression machinery?' are of major importance to the understanding of gene expression and regulation. The task of delineating exon--intron organization is even more challenging in vertebrates than in lower eukaryotes because an average vertebrate gene consists of multiple small exons separated by introns that are 10 or 100 times larger. As the Human Genome Project enters a large-scale sequencing phase, identifying exons has also become a bottle-neck in genome annotation. In the early 1980s, the splicing site consensus (1) and the weight matrix method (2) were developed by DNA sequence comparisons. Senapathy et al. (3) later compiled more comprehensive sequence statistics on major categories of GenBank release 57.0. The statistical features of promote

A novel approach to phylogenetic tree construction using stochastic optimization and clustering

Vesicular stomatitis virus glycoprotein G-pseudotyped mouse retroviral vectors have been used as mutagens for a large-scale insertional mutagenesis screen in the zebra fish. To reproducibly generate high-titer virus stocks, we devised a method for rapidly selecting cell lines that can yield high-titer viruses and isolated a producer cell line that yields virus at a high titer on zebra fish embryos. Virus produced from this line, designated GT virus, is nontoxic following injection of zebra fish blastulae and efficiently infects embryonic cells that give rise to the future germ line. Using GT virus preparations we generated roughly 500,000 germ line-transmissible proviral insertions in a population of 25,000 founder fish in about 2 months. The GT virus contains a gene trap, and trap events can be detected in the offspring of almost every founder fish. We discuss potential applications of this highly efficient method for generating germ line-transmissible insertions in a vertebrate A major task for biologists in the postgenome era is to determine the cellular and organismal functions of an estimated 30,000 human genes (24, 49). A powerful approach for functional determination is forward genetic screens in model organisms. By altering genes at random with mutagens and screening for abnormalities caused by the mutations, genetic screens have yielded large collections of mutants with defects in development, physiology, and/or behavior, and many of

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Global control of aberrant splice-site activation