Skip to main content
Yeast (Chichester, England) logoLink to Yeast (Chichester, England)

Estimation of Synteny Conservation and Genome Compaction Between Pufferfish (Fugu) and Human

Aoife McLysaght 1, Anton J Enright 1,2, Lucy Skrabanek 1, Kenneth H Wolfe 1,
PMCID: PMC2447035  PMID: 10797599

Abstract

Background: Knowledge of the amount of gene order and synteny conservation between two species gives insights to the extent and mechanisms of divergence. The vertebrate Fugu rubripes (pufferfish) has a small genome with little repetitive sequence which makes it attractive as a model genome. Genome compaction and synteny conservation between human and Fugu were studied using data from public databases.

Methods: Intron length and map positions of human and Fugu orthologues were compared to analyse relative genome compaction and synteny conservation respectivley. The divergence of these two genomes by genome rearrangement was simulated and the results were compared to the real data.

Results: Analysis of 199 introns in 22 orthologous genes showed an eight-fold average size reduction in Fugu, consistent with the ratio of total genome sizes. There was no consistent pattern relating the size reduction in individual introns or genes to gene base composition in either species. For genes that are neighbours in Fugu (genes from the same cosmid or GenBank entry), 40–50% have conserved synteny with a human chromosome. This figure may be underestimated by as much as two-fold, due to problems caused by incomplete human genome sequence data and the existence of dispersed gene families. Some genes that are neighbours in Fugu have human orthologues that are several megabases and tens of genes apart. This is probably caused by small inversions or other intrachromosomal rearrangements.

Conclusions: Comparison of observed data to computer simulations suggests that 4000–16 000 chromosomal rearrangements have occured since Fugu and human shared a common ancestor, implying a faster rate of rearrangement than seen in human/mouse comparisons.

Full Text

The Full Text of this article is available as a PDF (184.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Armes N., Gilley J., Fried M. The comparative genomic structure and sequence of the surfeit gene homologs in the puffer fish Fugu rubripes and their association with CpG-rich islands. Genome Res. 1997 Dec;7(12):1138–1152. doi: 10.1101/gr.7.12.1138. [DOI] [PubMed] [Google Scholar]
  3. Brenner S., Elgar G., Sandford R., Macrae A., Venkatesh B., Aparicio S. Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome. Nature. 1993 Nov 18;366(6452):265–268. doi: 10.1038/366265a0. [DOI] [PubMed] [Google Scholar]
  4. Brunner B., Todt T., Lenzner S., Stout K., Schulz U., Ropers H. H., Kalscheuer V. M. Genomic structure and comparative analysis of nine Fugu genes: conservation of synteny with human chromosome Xp22.2-p22.1. Genome Res. 1999 May;9(5):437–448. [PMC free article] [PubMed] [Google Scholar]
  5. Cottage A., Clark M., Hawker K., Umrania Y., Wheller D., Bishop M., Elgar G. Three receptor genes for plasminogen related growth factors in the genome of the puffer fish Fugu rubripes. FEBS Lett. 1999 Jan 29;443(3):370–374. doi: 10.1016/s0014-5793(99)00011-3. [DOI] [PubMed] [Google Scholar]
  6. Deloukas P., Schuler G. D., Gyapay G., Beasley E. M., Soderlund C., Rodriguez-Tomé P., Hui L., Matise T. C., McKusick K. B., Beckmann J. S. A physical map of 30,000 human genes. Science. 1998 Oct 23;282(5389):744–746. doi: 10.1126/science.282.5389.744. [DOI] [PubMed] [Google Scholar]
  7. Dickson D. Gene estimate rises as US and UK discuss freedom of access. Nature. 1999 Sep 23;401(6751):311–311. doi: 10.1038/43722. [DOI] [PubMed] [Google Scholar]
  8. Dunham I., Shimizu N., Roe B. A., Chissoe S., Hunt A. R., Collins J. E., Bruskiewich R., Beare D. M., Clamp M., Smink L. J. The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489–495. doi: 10.1038/990031. [DOI] [PubMed] [Google Scholar]
  9. Duret L., Mouchiroud D., Gautier C. Statistical analysis of vertebrate sequences reveals that long genes are scarce in GC-rich isochores. J Mol Evol. 1995 Mar;40(3):308–317. doi: 10.1007/BF00163235. [DOI] [PubMed] [Google Scholar]
  10. Ehrlich J., Sankoff D., Nadeau J. H. Synteny conservation and chromosome rearrangements during mammalian evolution. Genetics. 1997 Sep;147(1):289–296. doi: 10.1093/genetics/147.1.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Elgar G., Clark M. S., Meek S., Smith S., Warner S., Edwards Y. J., Bouchireb N., Cottage A., Yeo G. S., Umrania Y. Generation and analysis of 25 Mb of genomic DNA from the pufferfish Fugu rubripes by sequence scanning. Genome Res. 1999 Oct;9(10):960–971. doi: 10.1101/gr.9.10.960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Elgar G. Quality not quantity: the pufferfish genome. Hum Mol Genet. 1996;5(Spec No):1437–1442. doi: 10.1093/hmg/5.supplement_1.1437. [DOI] [PubMed] [Google Scholar]
  13. Elgar G., Sandford R., Aparicio S., Macrae A., Venkatesh B., Brenner S. Small is beautiful: comparative genomics with the pufferfish (Fugu rubripes). Trends Genet. 1996 Apr;12(4):145–150. doi: 10.1016/0168-9525(96)10018-4. [DOI] [PubMed] [Google Scholar]
  14. Gates M. A., Kim L., Egan E. S., Cardozo T., Sirotkin H. I., Dougan S. T., Lashkari D., Abagyan R., Schier A. F., Talbot W. S. A genetic linkage map for zebrafish: comparative analysis and localization of genes and expressed sequences. Genome Res. 1999 Apr;9(4):334–347. [PubMed] [Google Scholar]
  15. Gellner K., Brenner S. Analysis of 148 kb of genomic DNA around the wnt1 locus of Fugu rubripes. Genome Res. 1999 Mar;9(3):251–258. [PMC free article] [PubMed] [Google Scholar]
  16. Gilley J., Fried M. Extensive gene order differences within regions of conserved synteny between the Fugu and human genomes: implications for chromosomal evolution and the cloning of disease genes. Hum Mol Genet. 1999 Jul;8(7):1313–1320. doi: 10.1093/hmg/8.7.1313. [DOI] [PubMed] [Google Scholar]
  17. Gyapay G., Schmitt K., Fizames C., Jones H., Vega-Czarny N., Spillett D., Muselet D., Prud'homme J. F., Dib C., Auffray C. A radiation hybrid map of the human genome. Hum Mol Genet. 1996 Mar;5(3):339–346. doi: 10.1093/hmg/5.3.339. [DOI] [PubMed] [Google Scholar]
  18. How G. F., Venkatesh B., Brenner S. Conserved linkage between the puffer fish (Fugu rubripes) and human genes for platelet-derived growth factor receptor and macrophage colony-stimulating factor receptor. Genome Res. 1996 Dec;6(12):1185–1191. doi: 10.1101/gr.6.12.1185. [DOI] [PubMed] [Google Scholar]
  19. Hurst L. D., Brunton C. F., Smith N. G. Small introns tend to occur in GC-rich regions in some but not all vertebrates. Trends Genet. 1999 Nov;15(11):437–439. doi: 10.1016/s0168-9525(99)01832-6. [DOI] [PubMed] [Google Scholar]
  20. Ikemura T., Wada K. Evident diversity of codon usage patterns of human genes with respect to chromosome banding patterns and chromosome numbers; relation between nucleotide sequence data and cytogenetic data. Nucleic Acids Res. 1991 Aug 25;19(16):4333–4339. doi: 10.1093/nar/19.16.4333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kenmochi N., Kawaguchi T., Rozen S., Davis E., Goodman N., Hudson T. J., Tanaka T., Page D. C. A map of 75 human ribosomal protein genes. Genome Res. 1998 May;8(5):509–523. doi: 10.1101/gr.8.5.509. [DOI] [PubMed] [Google Scholar]
  22. Loftus B. J., Kim U. J., Sneddon V. P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M. L., Barnstead M., Cronin L. Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295–308. doi: 10.1006/geno.1999.5927. [DOI] [PubMed] [Google Scholar]
  23. Lucassen A. M., Julier C., Beressi J. P., Boitard C., Froguel P., Lathrop M., Bell J. I. Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet. 1993 Jul;4(3):305–310. doi: 10.1038/ng0793-305. [DOI] [PubMed] [Google Scholar]
  24. Meyer A., Schartl M. Gene and genome duplications in vertebrates: the one-to-four (-to-eight in fish) rule and the evolution of novel gene functions. Curr Opin Cell Biol. 1999 Dec;11(6):699–704. doi: 10.1016/s0955-0674(99)00039-3. [DOI] [PubMed] [Google Scholar]
  25. Nadeau J. H., Sankoff D. Counting on comparative maps. Trends Genet. 1998 Dec;14(12):495–501. doi: 10.1016/s0168-9525(98)01607-2. [DOI] [PubMed] [Google Scholar]
  26. Nadeau J. H., Taylor B. A. Lengths of chromosomal segments conserved since divergence of man and mouse. Proc Natl Acad Sci U S A. 1984 Feb;81(3):814–818. doi: 10.1073/pnas.81.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Postlethwait J. H., Yan Y. L., Gates M. A., Horne S., Amores A., Brownlie A., Donovan A., Egan E. S., Force A., Gong Z. Vertebrate genome evolution and the zebrafish gene map. Nat Genet. 1998 Apr;18(4):345–349. doi: 10.1038/ng0498-345. [DOI] [PubMed] [Google Scholar]
  28. Poulter R., Butler M. A retrotransposon family from the pufferfish (fugu) Fugu rubripes. Gene. 1998 Jul 30;215(2):241–249. doi: 10.1016/s0378-1119(98)00296-0. [DOI] [PubMed] [Google Scholar]
  29. Reboul J., Gardiner K., Monneron D., Uzé G., Lutfalla G. Comparative genomic analysis of the interferon/interleukin-10 receptor gene cluster. Genome Res. 1999 Mar;9(3):242–250. [PMC free article] [PubMed] [Google Scholar]
  30. Sandford R., Sgotto B., Aparicio S., Brenner S., Vaudin M., Wilson R. K., Chissoe S., Pepin K., Bateman A., Chothia C. Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains. Hum Mol Genet. 1997 Sep;6(9):1483–1489. doi: 10.1093/hmg/6.9.1483. [DOI] [PubMed] [Google Scholar]
  31. Schuler G. D. Sequence mapping by electronic PCR. Genome Res. 1997 May;7(5):541–550. doi: 10.1101/gr.7.5.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Trower M. K., Orton S. M., Purvis I. J., Sanseau P., Riley J., Christodoulou C., Burt D., See C. G., Elgar G., Sherrington R. Conservation of synteny between the genome of the pufferfish (Fugu rubripes) and the region on human chromosome 14 (14q24.3) associated with familial Alzheimer disease (AD3 locus) Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1366–1369. doi: 10.1073/pnas.93.4.1366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wootton J. C., Federhen S. Analysis of compositionally biased regions in sequence databases. Methods Enzymol. 1996;266:554–571. doi: 10.1016/s0076-6879(96)66035-2. [DOI] [PubMed] [Google Scholar]

Articles from Yeast (Chichester, England) are provided here courtesy of Wiley

RESOURCES