A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Genetic investigations with many different bacteria have revealed parallelisms and some contrasts with the biology of higher forms. The successful application of selective enrichment techniques to the study of gene recombination in Escherichia coli (Tatum and Lederberg, 1947; Lederberg et al., 1951) suggested that a similar approach should be applied to other bacteria. This paper presents the results of such experiments with Salmonella typhimurium and other Salmonella serotypes. The mechanism of genetic exchange found in these experiments differs from sexual recombination in E. coli in many respects so as to warrant a new descriptive term, transduction. MATERIALS AND METHODS Most of the strains of S. typhimurium were provided by Lilleengen (1948) as representative of his 21 "phage types", LT-1 through LT-22. Most if not all strains of S. typhimurium are lysogenic (Boyd, 1950), and these have provided 12 lines of bacteriophage. Other cultures were obtained from F. Kauffmann, E. K. Borman, and P. R. Edwards. All cultures were maintained on nutrient agar slants. Specific growth factor dependent mutants (auxotrophs) were obtained from ultraviolet irradiated cell suspensions subjected to the penicillin method for selective isolation (Davis, 1950a; Lederberg and Zinder, 1948). Similar mutants have been obtained in Salmonella by Plough et al. (1951) and Bacon et al. (1951). Other methods for the isolation and characterization of auxotrophic and fermentation mutants have been documented elsewhere (Lederberg, 1950; Lederberg and Lederberg, 1952). Streptomycin resistant mutants were selected by plating dense, unirradiated cell suspensions into agar containing 500 mg per L of dihydrostreptomycin. "Complete" indicator medium (EMB) was made up from the same formula as for E. coli (Lederberg, 1950). The defined eosin methylene blue medium ("EML agar") containedin g per L: sodium lactate, 2.5; (NH4)2SO4, 5; NaCl, 1; MgSO4, 1; K2HPO4, 2; methylene blue hydrochloride, 0.05; eosin Y, 0.3; and agar, 15. Difco products, penassay broth, and nutrient agar, were employed as "complete" media.

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