overlapping genes


Summary: Genes whose nucleotide sequences overlap to some degree. The overlapped sequences may involve structural or regulatory genes of eukaryotic or prokaryotic cells.

Top Publications

  1. Pavesi A. Pattern of nucleotide substitution in the overlapping nonstructural genes of influenza A virus and implication for the genetic diversity of the H5N1 subtype. Gene. 2007;402:28-34 pubmed
    In viruses under strong pressure to minimize genome size, overlapping genes represent a fine strategy to condense a maximum amount of information into short nucleotide sequences...
  2. Johnson Z, Chisholm S. Properties of overlapping genes are conserved across microbial genomes. Genome Res. 2004;14:2268-72 pubmed
    ..Here we show that overlapping genes are a consistent feature (approximately one-third of all genes) across all microbial genomes sequenced to ..
  3. Shmulevitz M, Yameen Z, Dawe S, Shou J, O Hara D, Holmes I, et al. Sequential partially overlapping gene arrangement in the tricistronic S1 genome segments of avian reovirus and Nelson Bay reovirus: implications for translation initiation. J Virol. 2002;76:609-18 pubmed
    ..These results suggest that translation initiation complexes can bypass over 600 nucleotides and two functional overlapping upstream ORFs in order to access the distal final sigmaC start site...
  4. Luo Y, Fu C, Zhang D, Lin K. BPhyOG: an interactive server for genome-wide inference of bacterial phylogenies based on overlapping genes. BMC Bioinformatics. 2007;8:266 pubmed
    b>Overlapping genes (OGs) in bacterial genomes are pairs of adjacent genes of which the coding sequences overlap partly or entirely. With the rapid accumulation of sequence data, many OGs in bacterial genomes have now been identified...
  5. McGirr K, Buehuring G. Tax & rex: overlapping genes of the Deltaretrovirus group. Virus Genes. 2006;32:229-39 pubmed
  6. Scherer S, Cheung J, MacDonald J, Osborne L, Nakabayashi K, Herbrick J, et al. Human chromosome 7: DNA sequence and biology. Science. 2003;300:767-72 pubmed
    ..This approach enabled the discovery of candidate genes for developmental diseases including autism. ..
  7. Firth A, Atkins J. Bioinformatic analysis suggests that the Cypovirus 1 major core protein cistron harbours an overlapping gene. Virol J. 2008;5:62 pubmed publisher
    ..The ORFX amino acid sequences are hydrophilic and basic, with between 12 and 16 Arg/Lys residues in each though, at 7.5-10.2 kDa, the putative ORFX product is too small to appear on typical published protein gels...
  8. Barrette I, McKenna S, Taylor D, Forsdyke D. Introns resolve the conflict between base order-dependent stem-loop potential and the encoding of RNA or protein: further evidence from overlapping genes. Gene. 2001;270:181-9 pubmed
    ..Purine-loading pressure would also have favoured intron formation. ..
  9. Zhou C, Blumberg B. Overlapping gene structure of human VLCAD and DLG4. Gene. 2003;305:161-6 pubmed
    ..Interestingly, VLCAD and DLG4 genes do not overlap in the mouse or Drosophila genomes. ..

More Information


  1. Kingsford C, Delcher A, Salzberg S. A unified model explaining the offsets of overlapping and near-overlapping prokaryotic genes. Mol Biol Evol. 2007;24:2091-8 pubmed
    b>Overlapping genes are a common phenomenon. Among sequenced prokaryotes, more than 29% of all annotated genes overlap at least 1 of their 2 flanking genes...
  2. Chung B, Miller W, Atkins J, Firth A. An overlapping essential gene in the Potyviridae. Proc Natl Acad Sci U S A. 2008;105:5897-902 pubmed publisher
    ..This discovery suggests that other short overlapping genes may remain hidden even in well studied virus genomes (as well as cellular organisms) and demonstrates the ..
  3. Sakharkar K, Chow V. Strategies for genome reduction in microbial genomes. Genome Inform. 2005;16:69-75 pubmed
    Niche dependent differential gene loss and overlapping genes have been proposed as means of achieving genome reduction by retaining indispensable genes and compressing maximum amount of information in available sequence space...
  4. Veeramachaneni V, Makałowski W, Galdzicki M, Sood R, Makałowska I. Mammalian overlapping genes: the comparative perspective. Genome Res. 2004;14:280-6 pubmed
    ..Thousands of overlapping genes were recently identified in the human and mouse genomes...
  5. Karlin S, Chen C, Gentles A, Cleary M. Associations between human disease genes and overlapping gene groups and multiple amino acid runs. Proc Natl Acad Sci U S A. 2002;99:17008-13 pubmed
    ..Typically, the two overlapping genes are encoded on opposite DNA strands. OGGs are often associated with specific disease phenotypes...
  6. Dan I, Watanabe N, Kajikawa E, Ishida T, Pandey A, Kusumi A. Overlapping of MINK and CHRNE gene loci in the course of mammalian evolution. Nucleic Acids Res. 2002;30:2906-10 pubmed
    ..Because CHRNE and MINK are differentially expressed, the potentially hazardous mutations responsible for the exon overlap seem to have escaped evolutionary pressures by differential temporo-spatial expression of the two genes. ..
  7. Shintani S, O hUigin C, Toyosawa S, Michalov V, Klein J. Origin of gene overlap: the case of TCP1 and ACAT2. Genetics. 1999;152:743-54 pubmed
    ..One or both of the transposed genes found by chance signals that are necessary for the processing of their transcripts to be present on the noncoding strand of the partner gene...
  8. Pallejà A, Harrington E, Bork P. Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?. BMC Genomics. 2008;9:335 pubmed publisher
    Across the fully sequenced microbial genomes there are thousands of examples of overlapping genes. Many of these are only a few nucleotides long and are thought to function by permitting the coordinated regulation of gene expression...
  9. Sanna C, Li W, Zhang L. Overlapping genes in the human and mouse genomes. BMC Genomics. 2008;9:169 pubmed publisher
    Increasing evidence suggests that overlapping genes are much more common in eukaryotic genomes than previously thought...
  10. Firth A. Bioinformatic analysis suggests that the Orbivirus VP6 cistron encodes an overlapping gene. Virol J. 2008;5:48 pubmed publisher
    ..These viruses have linear dsRNA genomes divided into ten segments, all of which have previously been assumed to be monocistronic...
  11. Rancurel C, Khosravi M, Dunker A, Romero P, Karlin D. Overlapping genes produce proteins with unusual sequence properties and offer insight into de novo protein creation. J Virol. 2009;83:10719-36 pubmed publisher
    ..Another mechanism of protein birth is provided by overlapping genes. They are created de novo by mutations within a coding sequence that lead to the expression of a novel ..
  12. Firth A, Brown C. Detecting overlapping coding sequences with pairwise alignments. Bioinformatics. 2005;21:282-92 pubmed
    ..The algorithms should prove useful for detecting novel overlapping genes--especially short coding ORFs in viruses. Programs may be obtained from the authors. http://biochem.otago.ac...
  13. Kennerson M, Nassif N, Dawkins J, Dekroon R, Yang J, Nicholson G. The Charcot-Marie-Tooth binary repeat contains a gene transcribed from the opposite strand of a partially duplicated region of the COX10 gene. Genomics. 1997;46:61-9 pubmed
    ..The presence of expressed sequences in both elements of the CMT1A-REP binary repeat could explain the maintenance of this repeat in humans. ..
  14. Pavesi A. Detection of signature sequences in overlapping genes and prediction of a novel overlapping gene in hepatitis G virus. J Mol Evol. 2000;50:284-95 pubmed
    In viruses an increased coding ability is provided by overlapping genes, in which two alternative open reading frames (ORFs) may be translated to yield two distinct proteins...
  15. Sabath N, Graur D, Landan G. Same-strand overlapping genes in bacteria: compositional determinants of phase bias. Biol Direct. 2008;3:36 pubmed publisher
    Same-strand overlapping genes may occur in frameshifts of one (phase 1) or two nucleotides (phase 2). In previous studies of bacterial genomes, long phase-1 overlaps were found to be more numerous than long phase-2 overlaps...
  16. Rogozin I, Spiridonov A, Sorokin A, Wolf Y, Jordan I, Tatusov R, et al. Purifying and directional selection in overlapping prokaryotic genes. Trends Genet. 2002;18:228-32 pubmed
    In overlapping genes, the same DNA sequence codes for two proteins using different reading frames. Analysis of overlapping genes can help in understanding the mode of evolution of a coding region from noncoding DNA...
  17. Zhang D, Chen J, Deng L, Mao Q, Zheng J, Wu J, et al. Evolutionary selection associated with the multi-function of overlapping genes in the hepatitis B virus. Infect Genet Evol. 2010;10:84-8 pubmed publisher
    It is a challenge to understand the discrete roles of each point mutation in viral evolution, but overlapping genes provide an excellent entrance for the investigation of this complicated process...
  18. Zaaijer H, van Hemert F, Koppelman M, Lukashov V. Independent evolution of overlapping polymerase and surface protein genes of hepatitis B virus. J Gen Virol. 2007;88:2137-43 pubmed
    ..Evolutionary constraints in overlapping genes have been demonstrated for many viruses, with one of the two overlapping genes being subjected to positive ..
  19. Kim D, Cho C, Huh J, Kim H, Cho H. EVOG: a database for evolutionary analysis of overlapping genes. Nucleic Acids Res. 2009;37:D698-702 pubmed publisher
    b>Overlapping genes are defined as a pair of genes whose transcripts are overlapped...
  20. Iwabe N, Miyata T. Overlapping genes in parasitic protist Giardia lamblia. Gene. 2001;280:163-7 pubmed
    ..We describe here the presence of overlapping genes in G...
  21. Soldà G, Suyama M, Pelucchi P, Boi S, Guffanti A, Rizzi E, et al. Non-random retention of protein-coding overlapping genes in Metazoa. BMC Genomics. 2008;9:174 pubmed publisher
    ..For all analyzed species the observed number of overlapping genes is always lower than expected assuming functional neutrality, suggesting that gene overlap is negatively ..
  22. Firth A, Brown C. Detecting overlapping coding sequences in virus genomes. BMC Bioinformatics. 2006;7:75 pubmed
    ..of codon usage; conservation between related sequences can be difficult to interpret--especially within overlapping genes; and viruses often employ non-canonical translational mechanisms--e.g...
  23. Pavesi A. Origin and evolution of overlapping genes in the family Microviridae. J Gen Virol. 2006;87:1013-7 pubmed
    ..ancestral and derived frames was carried out by comparing the patterns of codon usage in overlapping and non-overlapping genes. By this approach, a gradual increase in complexity of the phage genome--from an ancestral state lacking ..
  24. Firth A, Atkins J. Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning. Virol J. 2010;7:17 pubmed publisher
    b>Overlapping genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of overlapping genes can be difficult using conventional gene-finding software...
  25. Sakharkar K, Sakharkar M, Verma C, Chow V. Comparative study of overlapping genes in bacteria, with special reference to Rickettsia prowazekii and Rickettsia conorii. Int J Syst Evol Microbiol. 2005;55:1205-9 pubmed
    b>Overlapping genes have been proposed as a means of achieving genome reduction by compressing the maximum amount of information in limited sequence space...
  26. Firth A, Atkins J. Analysis of the coding potential of the partially overlapping 3' ORF in segment 5 of the plant fijiviruses. Virol J. 2009;6:32 pubmed publisher
    ..Possible translation mechanisms for this unusually positioned ORF are discussed. ..
  27. Makalowska I, Lin C, Makalowski W. Overlapping genes in vertebrate genomes. Comput Biol Chem. 2005;29:1-12 pubmed
    b>Overlapping genes in mammalian genomes are unexpected phenomena even though hundreds of pairs of protein coding overlapping genes have been reported so far...
  28. Fukuda Y, Nakayama Y, Tomita M. On dynamics of overlapping genes in bacterial genomes. Gene. 2003;323:181-7 pubmed
    A genome-wide computational analysis of overlapping genes in various prokaryotic genomes was conducted to study the evolutionary rates of the formation and degradation of overlapping genes...
  29. Cooper P, Smilinich N, Day C, Nowak N, Reid L, Pearsall R, et al. Divergently transcribed overlapping genes expressed in liver and kidney and located in the 11p15.5 imprinted domain. Genomics. 1998;49:38-51 pubmed
  30. Sabath N, Price N, Graur D. A potentially novel overlapping gene in the genomes of Israeli acute paralysis virus and its relatives. Virol J. 2009;6:144 pubmed publisher
    ..We applied a recently developed method for the estimation of selection in overlapping genes to detect purifying selection and, hence, functionality...
  31. Nekrutenko A, Wadhawan S, Goetting Minesky P, Makova K. Oscillating evolution of a mammalian locus with overlapping reading frames: an XLalphas/ALEX relay. PLoS Genet. 2005;1:e18 pubmed
    ..This is the first example of a rapidly evolving locus encoding interacting proteins via overlapping reading frames, with a possible link to the origin of species-specific neurological differences. ..
  32. Lopez Gomollon S, Hernandez J, Pellicer S, Angarica V, Peleato M, Fillat M. Cross-talk between iron and nitrogen regulatory networks in anabaena (Nostoc) sp. PCC 7120: identification of overlapping genes in FurA and NtcA regulons. J Mol Biol. 2007;374:267-81 pubmed
    ..The identification of common elements overlapping the NtcA and FurA regulons allows us to establish a previously unrecognized transcriptional regulatory connection between iron homeostasis, redox control and nitrogen metabolism...
  33. Cheng C, Yang C, Chiu H, Lu C. Reconstructing genome trees of prokaryotes using overlapping genes. BMC Bioinformatics. 2010;11:102 pubmed publisher
    b>Overlapping genes (OGs) are defined as adjacent genes whose coding sequences overlap partially or entirely. In fact, they are ubiquitous in microbial genomes and more conserved between species than non-overlapping genes...
  34. Lillo F, Krakauer D. A statistical analysis of the three-fold evolution of genomic compression through frame overlaps in prokaryotes. Biol Direct. 2007;2:22 pubmed
    ..is frequently compressed, exploiting redundancies in the genetic code in order to store information in overlapping genes. We investigate the length, phase and orientation properties of overlap in 58 prokaryotic species evaluating ..
  35. Cock P, Whitworth D. Evolution of gene overlaps: relative reading frame bias in prokaryotic two-component system genes. J Mol Evol. 2007;64:457-62 pubmed
    ..However, these changes will be less detrimental to the original coding sequence if the two genes overlap in phase +1, leading to selective retention during evolution of phase +1 overlaps relative to phase +2 overlaps. ..
  36. Hastings M, Milcarek C, Martincic K, Peterson M, Munroe S. Expression of the thyroid hormone receptor gene, erbAalpha, in B lymphocytes: alternative mRNA processing is independent of differentiation but correlates with antisense RNA levels. Nucleic Acids Res. 1997;25:4296-300 pubmed
    ..The correlation between RevErb and erbAalpha mRNA is consistent with negative regulation of alpha2 via antisense interactions with the complementary RevErb mRNA. ..
  37. Krakauer D. Stability and evolution of overlapping genes. Evolution. 2000;54:731-9 pubmed
    ..sequence of nucleotides codes for regions of more than one functional polypeptide, this sequence contains overlapping genes. Overlap is most common in rapidly evolving genomes with high mutation rates such as viruses, bacteria, and ..
  38. Pedersen A, Jensen J. A dependent-rates model and an MCMC-based methodology for the maximum-likelihood analysis of sequences with overlapping reading frames. Mol Biol Evol. 2001;18:763-76 pubmed
    ..Finally, we present an extended model, together with a simpler approximate estimation procedure, and use this to test the adequacy of the former model. ..
  39. Belshaw R, Pybus O, Rambaut A. The evolution of genome compression and genomic novelty in RNA viruses. Genome Res. 2007;17:1496-504 pubmed
    ..One aspect of their small size is the genome compression caused by the use of overlapping genes (where some nucleotides code for two genes)...
  40. Sabath N, Landan G, Graur D. A method for the simultaneous estimation of selection intensities in overlapping genes. PLoS ONE. 2008;3:e3996 pubmed publisher
    ..Recently, it has been reported that overlapping genes, which are ubiquitous in all domains of life, seem to exhibit inordinate degrees of positive selection...
  41. Firth A, Atkins J. Bioinformatic analysis suggests that a conserved ORF in the waikaviruses encodes an overlapping gene. Arch Virol. 2008;153:1379-83 pubmed publisher
    ..With the exception of Theiler's virus, overlapping genes are essentially unknown in the order...
  42. Bhasin R, Freundlich M. The nucleotide sequence of the Escherichia coli crp divergent RNA and an overlapping ORF. Biochim Biophys Acta. 1991;1129:109-11 pubmed
    ..These putative termination sites may account for the two RNAs of approximately 300 and 550 nucleotides previously identified as originating from the crp divergent promoter. ..
  43. Matsuzaka Y, Tounai K, Denda A, Tomizawa M, Makino S, Okamoto K, et al. Identification of novel candidate genes in the diffuse panbronchiolitis critical region of the class I human MHC. Immunogenetics. 2002;54:301-9 pubmed
    ..Taken together, these results, especially the abundant expression in lung, indicate that C6orf37 and C6orf37OS are excellent candidate genes for DPB. ..
  44. Lesniewicz K, Lüscher Firzlaff J, Poreba E, Fuchs P, Walsemann G, Wiche G, et al. Overlap of the gene encoding the novel poly(ADP-ribose) polymerase Parp10 with the plectin 1 gene and common use of exon sequences. Genomics. 2005;86:38-46 pubmed
    ..Furthermore our findings suggest that at least one of the plectin 1 promoters is located within intron 9 of the Parp10 gene. ..
  45. Takizawa T, Anderson C, Robinson J. A novel Fc gamma R-defined, IgG-containing organelle in placental endothelium. J Immunol. 2005;175:2331-9 pubmed
    ..No IgG-containing organelles are associated with caveolin. These findings are compatible with Fc gammaRIIb-mediated transfer of IgG across the villus endothelium, independent of caveolae. ..
  46. Kafri R, Dahan O, Levy J, Pilpel Y. Preferential protection of protein interaction network hubs in yeast: evolved functionality of genetic redundancy. Proc Natl Acad Sci U S A. 2008;105:1243-8 pubmed publisher
    ..Our results suggest an intriguing conclusion-although redundancy is typically transient on evolutionary time scales, it tends to be preserved among some of the central proteins in the cellular interaction network. ..
  47. Xu Z, Wei W, Gagneur J, Perocchi F, Clauder Münster S, Camblong J, et al. Bidirectional promoters generate pervasive transcription in yeast. Nature. 2009;457:1033-7 pubmed publisher
  48. Kardalinou E, Eick S, Albig W, Doenecke D. Association of a human H1 histone gene with an H2A pseudogene and genes encoding H2B.1 and H3.1 histones. J Cell Biochem. 1993;52:375-83 pubmed
    ..The same arrangement of an H3 gene, an H2A pseudogene and an H2B gene downstream of an H1 gene has been described within a mouse histone gene cluster [Yang et al.:J Biol Chem 262:17118-17125, 1987; Gruber et al.:Gene 95:303-304, 1990]. ..
  49. Leggett B, Young J, Buttenshaw R, Thomas L, Young B, Chenevix Trench G, et al. Colorectal carcinomas show frequent allelic loss on the long arm of chromosome 17 with evidence for a specific target region. Br J Cancer. 1995;71:1070-3 pubmed
    ..This suggests the target of allelic loss on 17q is a tumour-suppressor gene in this region. ..
  50. Popov A, Bützler C, Frippiat J, Lefranc M, Bruggemann M. Assembly and extension of yeast artificial chromosomes to build up a large locus. Gene. 1996;177:195-201 pubmed
    ..This approach made it possible to assemble and extend large YACs from an unlimited number of smaller overlapping YACs by positive-negative selection. ..
  51. Miller P, Sulavik M. Overlaps and parallels in the regulation of intrinsic multiple-antibiotic resistance in Escherichia coli. Mol Microbiol. 1996;21:441-8 pubmed
    ..The observed resistance to clinically important antibiotics appears to reflect an overlap with broad-ranged adaptive responses by free-living bacteria to noxious plant materials in their natural environment. ..
  52. Stålberg K, Ellerstöm M, Ezcurra I, Ablov S, Rask L. Disruption of an overlapping E-box/ABRE motif abolished high transcription of the napA storage-protein promoter in transgenic Brassica napus seeds. Planta. 1996;199:515-9 pubmed
    ..Similar results have been obtained by analysing some of the constructs in transgenic tobacco, suggesting that many of the cis-elements in the napA promoter are conserved, at least in dicotyledonous species. ..
  53. Ng S, Perkins L, Conboy G, Perrimon N, Fishman M. A Drosophila gene expressed in the embryonic CNS shares one conserved domain with the mammalian GAP-43. Development. 1989;105:629-38 pubmed
    ..These cells appear to include at least one specific set of glia that may establish scaffolding for the development of the longitudinal neuropile. ..