Genetic Sequence Databases


From elucidation of the first protein sequence to publication of the human genome, sequence information has been transformative. High‐throughput technologies created torrents of genomic data, which needed to be annotated and stored for use in research. The sequencing revolution was remarkable; what made it a ‘game changer’ was the simultaneous innovation in Web technologies that opened the Internet to mass audiences and gave scientists the unique ability to collect, organise and immediately share information – the impact was huge. The cottage industry of sequence collection assumed industrial proportions, requiring worldwide cooperation to harness the deluge. Today, internationally available databases house the sequences of genes, information about their encoded proteins, their functions, disease associations and so on. Capturing data from worldwide genome projects, and making them freely available for research, these repositories continue to support the ongoing quest to understand our genetic ancestry and to address major challenges in the health, pharmaceutical and agricultural industries.

Key Concepts

  • Sequence information became available slowly, from pioneering work on the manual sequencing of proteins.
  • Elucidating nucleotide sequences was technically more difficult because of the size of DNA molecules.
  • Once molecular sequences were published, enthusiasts began to collect them in databases (the first ‘database’ was actually a book!).
  • Automatic, and then high‐throughput, technologies changed the pace of sequencing, and made whole‐genome sequencing feasible for the first time.
  • Landmark genome‐sequencing projects ushered in a new era of data generation.
  • The arrival of Web technologies coincided with the emergence of high‐throughput sequencing capabilities, and led to a proliferation of biological databases.
  • Sequence data are now generated on such a scale that the information has to be gathered via international consortia.
  • The first nucleotide sequence databases were the EMBL data library, GenBank and DDBJ, which now cooperate under the auspices of the INSDC.
  • Amongst the first protein sequence databases were the PIR‐PSD, Swiss‐Prot and TrEMBL, which now pool resources under the umbrella resource, UniProt.
  • Sequence databases play pivotal roles in all aspects of life‐science research, and will continue to make important contributions to research in the health, pharmaceutical and agricultural sciences.

Keywords: ENA; GenBank; DDBJ; Swiss‐Prot; TrEMBL; PIR; UniProt; Internet; sequence; genome

Figure 1. Landmark events in the dawning of the genomic era. Flags beneath the timeline show how changes in sequencing technology (from the appearance of automated peptide sequencers in the 1960s, to DNA sequencing in the 1970s and high‐throughput (HT) techniques in the early 1990s) led from manual peptide sequencing of the first hormone in 1955 and enzyme in 1965 to the flood of completed genomes in the mid‐1990s. Echoing the information boom (flags above the timeline), databases began to proliferate in the 1980s, starting with relatively simple sequence repositories, through individual family databases, organism‐specific databases, molecular interaction and pathway databases, to integrated databases of protein families and functional sites. The birth of the Web (WWW) in the early 1990s provided a vehicle for rapid dissemination of the data deluge throughout the world.
Figure 2. Format of a typical EMBL entry: the luxF gene from Photobacterium phosphoreum. The two‐letter code at the beginning of each line indicates the type of information contained in that line. The entry contains an identifier (ID), an accession number (AC) – here, both M22128 – and a literature cross‐reference (RN, RP, RX, etc.); the sequence field (SQ) contains the nucleotide sequence, and the coding sequence (CDS) field of the feature table (FT) its protein translation. Note the cross‐references to UniProtKB/Swiss‐Prot (Figure) and the PDB (Figure) in the database cross‐reference (db_xref) lines within the feature table. Ellipses denote lines deleted for brevity.
Figure 3. Format of a typical UniProtKB/Swiss‐Prot entry: the nonfluorescent flavoprotein from P. phosphoreum (whose gene sequence is shown in the EMBL entry in Figure). The two‐letter code at the beginning of each line adheres to the EMBL format and indicates the type of information contained in that line. Note the detailed annotations: the entry includes the identifier (ID) and the accession number (AC) lines – here, LUXF_PHOPO and P12745, respectively; several literature cross‐references (RN, RP, RX, etc.); a free‐text comment field (CC), describing the protein's cofactor, subunit structure and family relationships; a large number of database cross‐references (DR); a feature table (FT), describing elements of the 3D structure and their locations; and the amino acid sequence itself (SQ). Note the reciprocal cross‐reference to EMBL, plus the link to the PDB, in the DR lines in the centre of the figure. Ellipses denote lines deleted for brevity.
Figure 4. Format of a typical UniProtKB/TrEMBL entry: the nonfluorescent flavoprotein from Photobacterium leiognathi. The two‐letter code at the beginning of each line adheres to the EMBL format and indicates the type of information contained in that line. The information included in the entry is generated automatically and is hence more limited than that typically found in UniProtKB/Swiss‐Prot entries (Figure). Notable absences are the free‐text comment field (CC) and the substantial feature table (FT). Note the reciprocal cross‐reference to EMBL in the DR lines in the centre of the figure.
Figure 5. Computer‐generated image of the structure of flavoprotein 390 from P. phosphoreum (1FVP), whose related EMBL and UniProtKB/Swiss‐Prot entries are illustrated in Figures and , respectively. Local helical structures (α‐helices) are red, and extended ribbons (β‐strands) are yellow. The image was generated using the NGL Viewer (Rose and Hildebrand, ).


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Further Reading

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Attwood, Teresa K(Apr 2018) Genetic Sequence Databases. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005312.pub3]