The Sequence of the Human Genome

Abstract

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.

Expanding the organismal scope of proteomics: Cross‐species protein identification by mass spectrometry and its implications

“…The first living organism to be sequenced was Haemophilus influenzae, in 1995. Since the completion of the first genome, many unicellular and multicellular eukaryotic organisms' genomes have been sequenced, including Sacharomyces cerevisiae, Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana, and the crowning achievement of the first draft assembly of the human genome [41,42]. Genomic sequencing continues at a very high rate with the completion of a new organism every few months.…”

Effects of Template Sequence and Secondary Structure on DNA-Templated Reactivity

“…a The results for 10a/11a under reductive amination conditions and 10b/ 11b under amine acylation conditions are given for each of the templates after 8 h. Templates with intervening secondary structures that bring the reactive ends closest together (25 and 26) lead to the highest product yields for the end-of-helix reagent 10. Each of the templates with designed secondary structures (23)(24)(25)(26) reacts efficiently with the omega architecture reagent 11.…”

Neuropeptidomics: MS Applied to the Discovery of Novel Peptides from the Brain

“…he characterization of genomes of an ever-growing number of species, including the human genome, has provided new technologies and theories necessary to tackle the evaluation of very complex biological systems (1)(2)(3). In the field of proteomics, valuable information about the function of the molecular products encoded in the genome is obtained, and modern proteomics approaches have significantly improved the possibilities for highthroughput identification of proteins.…”