Skip to main content
Proceedings of the Royal Society B: Biological Sciences logoLink to Proceedings of the Royal Society B: Biological Sciences
. 2003 Jul 7;270(1522):1331–1340. doi: 10.1098/rspb.2003.2383

Towards the delineation of the ancestral eutherian genome organization: comparative genome maps of human and the African elephant (Loxodonta africana) generated by chromosome painting.

Lutz Frönicke 1, Johannes Wienberg 1, Gary Stone 1, Lisa Adams 1, Roscoe Stanyon 1
PMCID: PMC1691379  PMID: 12965023

Abstract

This study presents a whole-genome comparison of human and a representative of the Afrotherian clade, the African elephant, generated by reciprocal Zoo-FISH. An analysis of Afrotheria genomes is of special interest, because recent DNA sequence comparisons identify them as the oldest placental mammalian clade. Complete sets of whole-chromosome specific painting probes for the African elephant and human were constructed by degenerate oligonucleotide-primed PCR amplification of flow-sorted chromosomes. Comparative genome maps are presented based on their hybridization patterns. These maps show that the elephant has a moderately rearranged chromosome complement when compared to humans. The human paint probes identified 53 evolutionary conserved segments on the 27 autosomal elephant chromosomes and the X chromosome. Reciprocal experiments with elephant probes delineated 68 conserved segments in the human genome. The comparison with a recent aardvark and elephant Zoo-FISH study delineates new chromosomal traits which link the two Afrotherian species phylogenetically. In the absence of any morphological evidence the chromosome painting data offer the first non-DNA sequence support for an Afrotherian clade. The comparative human and elephant genome maps provide new insights into the karyotype organization of the proto-afrotherian, the ancestor of extant placental mammals, which most probably consisted of 2n=46 chromosomes.

Full Text

The Full Text of this article is available as a PDF (487.7 KB).

Selected References

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

  1. Bielec P. E., Gallagher D. S., Womack J. E., Busbee D. L. Homologies between human and dolphin chromosomes detected by heterologous chromosome painting. Cytogenet Cell Genet. 1998;81(1):18–25. doi: 10.1159/000015002. [DOI] [PubMed] [Google Scholar]
  2. Breen M., Thomas R., Binns M. M., Carter N. P., Langford C. F. Reciprocal chromosome painting reveals detailed regions of conserved synteny between the karyotypes of the domestic dog (Canis familiaris) and human. Genomics. 1999 Oct 15;61(2):145–155. doi: 10.1006/geno.1999.5947. [DOI] [PubMed] [Google Scholar]
  3. Carter N. P. Cytogenetic analysis by chromosome painting. Cytometry. 1994 Mar 15;18(1):2–10. doi: 10.1002/cyto.990180103. [DOI] [PubMed] [Google Scholar]
  4. Chowdhary B. P., Frönicke L., Gustavsson I., Scherthan H. Comparative analysis of the cattle and human genomes: detection of ZOO-FISH and gene mapping-based chromosomal homologies. Mamm Genome. 1996 Apr;7(4):297–302. doi: 10.1007/s003359900086. [DOI] [PubMed] [Google Scholar]
  5. Chowdhary B. P., Raudsepp T., Frönicke L., Scherthan H. Emerging patterns of comparative genome organization in some mammalian species as revealed by Zoo-FISH. Genome Res. 1998 Jun;8(6):577–589. doi: 10.1101/gr.8.6.577. [DOI] [PubMed] [Google Scholar]
  6. Clark M. S. Comparative genomics: the key to understanding the Human Genome Project. Bioessays. 1999 Feb;21(2):121–130. doi: 10.1002/(SICI)1521-1878(199902)21:2<121::AID-BIES6>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  7. Dauwerse J. G., Jumelet E. A., Wessels J. W., Saris J. J., Hagemeijer A., Beverstock G. C., van Ommen G. J., Breuning M. H. Extensive cross-homology between the long and the short arm of chromosome 16 may explain leukemic inversions and translocations. Blood. 1992 Mar 1;79(5):1299–1304. [PubMed] [Google Scholar]
  8. Dixkens C., Klett C., Bruch J., Kollak A., Serov O. L., Zhdanova N., Vogel W., Hameister H. ZOO-FISH analysis in insectivores: "Evolution extols the virtue of the status quo". Cytogenet Cell Genet. 1998;80(1-4):61–67. doi: 10.1159/000014958. [DOI] [PubMed] [Google Scholar]
  9. Eichler E. E. Masquerading repeats: paralogous pitfalls of the human genome. Genome Res. 1998 Aug;8(8):758–762. doi: 10.1101/gr.8.8.758. [DOI] [PubMed] [Google Scholar]
  10. Eizirik E., Murphy W. J., O'Brien S. J. Molecular dating and biogeography of the early placental mammal radiation. J Hered. 2001 Mar-Apr;92(2):212–219. doi: 10.1093/jhered/92.2.212. [DOI] [PubMed] [Google Scholar]
  11. Ferguson-Smith M. A. Genetic analysis by chromosome sorting and painting: phylogenetic and diagnostic applications. Eur J Hum Genet. 1997 Sep-Oct;5(5):253–265. [PubMed] [Google Scholar]
  12. Frönicke L., Chowdhary B. P., Scherthan H., Gustavsson I. A comparative map of the porcine and human genomes demonstrates ZOO-FISH and gene mapping-based chromosomal homologies. Mamm Genome. 1996 Apr;7(4):285–290. doi: 10.1007/s003359900084. [DOI] [PubMed] [Google Scholar]
  13. Frönicke L., Müller-Navia J., Romanakis K., Scherthan H. Chromosomal homeologies between human, harbor seal (Phoca vitulina) and the putative ancestral carnivore karyotype revealed by Zoo-FISH. Chromosoma. 1997 Jul;106(2):108–113. doi: 10.1007/s004120050230. [DOI] [PubMed] [Google Scholar]
  14. Frönicke L., Scherthan H. Zoo-fluorescence in situ hybridization analysis of human and Indian muntjac karyotypes (Muntiacus muntjak vaginalis) reveals satellite DNA clusters at the margins of conserved syntenic segments. Chromosome Res. 1997 Jun;5(4):254–261. doi: 10.1023/B:CHRO.0000032298.22346.46. [DOI] [PubMed] [Google Scholar]
  15. Frönicke L., Wienberg J. Comparative chromosome painting defines the high rate of karyotype changes between pigs and bovids. Mamm Genome. 2001 Jun;12(6):442–449. doi: 10.1007/s003350010288. [DOI] [PubMed] [Google Scholar]
  16. Glas R., Marshall Graves J. A., Toder R., Ferguson-Smith M., O'Brien P. C. Cross-species chromosome painting between human and marsupial directly demonstrates the ancient region of the mammalian X. Mamm Genome. 1999 Nov;10(11):1115–1116. doi: 10.1007/s003359901174. [DOI] [PubMed] [Google Scholar]
  17. Goureau A., Yerle M., Schmitz A., Riquet J., Milan D., Pinton P., Frelat G., Gellin J. Human and porcine correspondence of chromosome segments using bidirectional chromosome painting. Genomics. 1996 Sep 1;36(2):252–262. doi: 10.1006/geno.1996.0460. [DOI] [PubMed] [Google Scholar]
  18. Graves Jennifer A. Marshall, Westerman Michael. Marsupial genetics and genomics. Trends Genet. 2002 Oct;18(10):517–521. doi: 10.1016/s0168-9525(02)02772-5. [DOI] [PubMed] [Google Scholar]
  19. Haig D. A brief history of human autosomes. Philos Trans R Soc Lond B Biol Sci. 1999 Aug 29;354(1388):1447–1470. doi: 10.1098/rstb.1999.0490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hameister H., Klett C., Bruch J., Dixkens C., Vogel W., Christensen K. Zoo-FISH analysis: the American mink (Mustela vison) closely resembles the cat karyotype. Chromosome Res. 1997 Feb;5(1):5–11. doi: 10.1023/a:1018433200553. [DOI] [PubMed] [Google Scholar]
  21. Houck M. L., Kumamoto A. T., Gallagher D. S., Jr, Benirschke K. Comparative cytogenetics of the African elephant (Loxodonta africana) and Asiatic elephant (Elephas maximus). Cytogenet Cell Genet. 2001;93(3-4):249–252. doi: 10.1159/000056992. [DOI] [PubMed] [Google Scholar]
  22. Hungerford D. A., Chandra H. S., Snyder R. L., Ulmer F. A., Jr Chromosomes of three elephants, two Asian (Elephas maximus) and one African (Loxodonta africana). Cytogenetics. 1966;5(3):243–246. [PubMed] [Google Scholar]
  23. Iannuzzi L., Di Meo G. P., Perucatti A., Incarnato D. Comparison of the human with the sheep genomes by use of human chromosome-specific painting probes. Mamm Genome. 1999 Jul;10(7):719–723. doi: 10.1007/s003359901078. [DOI] [PubMed] [Google Scholar]
  24. Jauch A., Wienberg J., Stanyon R., Arnold N., Tofanelli S., Ishida T., Cremer T. Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8611–8615. doi: 10.1073/pnas.89.18.8611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Korstanje R., O'Brien P. C., Yang F., Rens W., Bosma A. A., van Lith H. A., van Zutphen L. F., Ferguson-Smith M. A. Complete homology maps of the rabbit (Oryctolagus cuniculus) and human by reciprocal chromosome painting. Cytogenet Cell Genet. 1999;86(3-4):317–322. doi: 10.1159/000015325. [DOI] [PubMed] [Google Scholar]
  26. Madsen O., Scally M., Douady C. J., Kao D. J., DeBry R. W., Adkins R., Amrine H. M., Stanhope M. J., de Jong W. W., Springer M. S. Parallel adaptive radiations in two major clades of placental mammals. Nature. 2001 Feb 1;409(6820):610–614. doi: 10.1038/35054544. [DOI] [PubMed] [Google Scholar]
  27. Mouse Genome Sequencing Consortium. Waterston Robert H., Lindblad-Toh Kerstin, Birney Ewan, Rogers Jane, Abril Josep F., Agarwal Pankaj, Agarwala Richa, Ainscough Rachel, Alexandersson Marina. Initial sequencing and comparative analysis of the mouse genome. Nature. 2002 Dec 5;420(6915):520–562. doi: 10.1038/nature01262. [DOI] [PubMed] [Google Scholar]
  28. Murphy W. J., Eizirik E., O'Brien S. J., Madsen O., Scally M., Douady C. J., Teeling E., Ryder O. A., Stanhope M. J., de Jong W. W. Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science. 2001 Dec 14;294(5550):2348–2351. doi: 10.1126/science.1067179. [DOI] [PubMed] [Google Scholar]
  29. Müller S., Stanyon R., Finelli P., Archidiacono N., Wienberg J. Molecular cytogenetic dissection of human chromosomes 3 and 21 evolution. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):206–211. doi: 10.1073/pnas.97.1.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Müller S., Stanyon R., O'Brien P. C., Ferguson-Smith M. A., Plesker R., Wienberg J. Defining the ancestral karyotype of all primates by multidirectional chromosome painting between tree shrews, lemurs and humans. Chromosoma. 1999 Nov;108(6):393–400. doi: 10.1007/s004120050391. [DOI] [PubMed] [Google Scholar]
  31. Nash W. G., Wienberg J., Ferguson-Smith M. A., Menninger J. C., O'Brien S. J. Comparative genomics: tracking chromosome evolution in the family ursidae using reciprocal chromosome painting. Cytogenet Cell Genet. 1998;83(3-4):182–192. doi: 10.1159/000015176. [DOI] [PubMed] [Google Scholar]
  32. Novacek M. J. Mammalian phylogeny: shaking the tree. Nature. 1992 Mar 12;356(6365):121–125. doi: 10.1038/356121a0. [DOI] [PubMed] [Google Scholar]
  33. Pinkel D., Straume T., Gray J. W. Cytogenetic analysis using quantitative, high-sensitivity, fluorescence hybridization. Proc Natl Acad Sci U S A. 1986 May;83(9):2934–2938. doi: 10.1073/pnas.83.9.2934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rabbitts P., Impey H., Heppell-Parton A., Langford C., Tease C., Lowe N., Bailey D., Ferguson-Smith M., Carter N. Chromosome specific paints from a high resolution flow karyotype of the mouse. Nat Genet. 1995 Apr;9(4):369–375. doi: 10.1038/ng0495-369. [DOI] [PubMed] [Google Scholar]
  35. Raudsepp T., Frönicke L., Scherthan H., Gustavsson I., Chowdhary B. P. Zoo-FISH delineates conserved chromosomal segments in horse and man. Chromosome Res. 1996 Apr;4(3):218–225. doi: 10.1007/BF02254963. [DOI] [PubMed] [Google Scholar]
  36. Rettenberger G., Klett C., Zechner U., Bruch J., Just W., Vogel W., Hameister H. ZOO-FISH analysis: cat and human karyotypes closely resemble the putative ancestral mammalian karyotype. Chromosome Res. 1995 Dec;3(8):479–486. doi: 10.1007/BF00713962. [DOI] [PubMed] [Google Scholar]
  37. Richard F., Messaoudi C., Lombard M., Dutrillaux B. Chromosome homologies between man and mountain zebra (Equus zebra hartmannae) and description of a new ancestral synteny involving sequences homologous to human chromosomes 4 and 8. Cytogenet Cell Genet. 2001;93(3-4):291–296. doi: 10.1159/000057000. [DOI] [PubMed] [Google Scholar]
  38. Roca A. L., Georgiadis N., Pecon-Slattery J., O'Brien S. J. Genetic evidence for two species of elephant in Africa. Science. 2001 Aug 24;293(5534):1473–1477. doi: 10.1126/science.1059936. [DOI] [PubMed] [Google Scholar]
  39. Sargan D. R., Yang F., Squire M., Milne B. S., O'Brien P. C., Ferguson-Smith M. A. Use of flow-sorted canine chromosomes in the assignment of canine linkage, radiation hybrid, and syntenic groups to chromosomes: refinement and verification of the comparative chromosome map for dog and human. Genomics. 2000 Oct 15;69(2):182–195. doi: 10.1006/geno.2000.6334. [DOI] [PubMed] [Google Scholar]
  40. Scherthan H., Cremer T., Arnason U., Weier H. U., Lima-de-Faria A., Frönicke L. Comparative chromosome painting discloses homologous segments in distantly related mammals. Nat Genet. 1994 Apr;6(4):342–347. doi: 10.1038/ng0494-342. [DOI] [PubMed] [Google Scholar]
  41. Springer M. S., Cleven G. C., Madsen O., de Jong W. W., Waddell V. G., Amrine H. M., Stanhope M. J. Endemic African mammals shake the phylogenetic tree. Nature. 1997 Jul 3;388(6637):61–64. doi: 10.1038/40386. [DOI] [PubMed] [Google Scholar]
  42. Stanhope M. J., Waddell V. G., Madsen O., de Jong W., Hedges S. B., Cleven G. C., Kao D., Springer M. S. Molecular evidence for multiple origins of Insectivora and for a new order of endemic African insectivore mammals. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9967–9972. doi: 10.1073/pnas.95.17.9967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Stanyon Roscoe, Koehler U., Consigliere S. Chromosome painting reveals that galagos have highly derived karyotypes. Am J Phys Anthropol. 2002 Apr;117(4):319–326. doi: 10.1002/ajpa.10047. [DOI] [PubMed] [Google Scholar]
  44. Telenius H., Carter N. P., Bebb C. E., Nordenskjöld M., Ponder B. A., Tunnacliffe A. Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics. 1992 Jul;13(3):718–725. doi: 10.1016/0888-7543(92)90147-k. [DOI] [PubMed] [Google Scholar]
  45. Thomas M. G., Hagelberg E., Jone H. B., Yang Z., Lister A. M. Molecular and morphological evidence on the phylogeny of the Elephantidae. Proc Biol Sci. 2000 Dec 22;267(1461):2493–2500. doi: 10.1098/rspb.2000.1310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Thürig D. Zum Chromosomenbild des Afrikanischen Elefanten (loxodonta africana) unter Berücksichtigung des Sexchromatins. Acta Anat (Basel) 1970;75(1):6–12. [PubMed] [Google Scholar]
  47. Vignaud Patrick, Duringer Philippe, Mackaye Hassane Taïsso, Likius Andossa, Blondel Cécile, Boisserie Jean-Renaud, De Bonis Louis, Eisenmann Véra, Etienne Marie-Esther, Geraads Denis. Geology and palaeontology of the Upper Miocene Toros-Menalla hominid locality, Chad. Nature. 2002 Jul 11;418(6894):152–155. doi: 10.1038/nature00880. [DOI] [PubMed] [Google Scholar]
  48. Volleth M., Heller K. G., Pfeiffer R. A., Hameister H. A comparative ZOO-FISH analysis in bats elucidates the phylogenetic relationships between Megachiroptera and five microchiropteran families. Chromosome Res. 2002;10(6):477–497. doi: 10.1023/a:1020992330679. [DOI] [PubMed] [Google Scholar]
  49. Wienberg J., Jauch A., Stanyon R., Cremer T. Molecular cytotaxonomy of primates by chromosomal in situ suppression hybridization. Genomics. 1990 Oct;8(2):347–350. doi: 10.1016/0888-7543(90)90292-3. [DOI] [PubMed] [Google Scholar]
  50. Wienberg J., Stanyon R., Nash W. G., O'Brien P. C., Yang F., O'Brien S. J., Ferguson-Smith M. A. Conservation of human vs. feline genome organization revealed by reciprocal chromosome painting. Cytogenet Cell Genet. 1997;77(3-4):211–217. doi: 10.1159/000134579. [DOI] [PubMed] [Google Scholar]
  51. Yang F., Alkalaeva E. Z., Perelman P. L., Pardini A. T., Harrison W. R., O'Brien P. C. M., Fu B., Graphodatsky A. S., Ferguson-Smith M. A., Robinson T. J. Reciprocal chromosome painting among human, aardvark, and elephant (superorder Afrotheria) reveals the likely eutherian ancestral karyotype. Proc Natl Acad Sci U S A. 2003 Jan 24;100(3):1062–1066. doi: 10.1073/pnas.0335540100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Yang F., O'Brien P. C., Milne B. S., Graphodatsky A. S., Solanky N., Trifonov V., Rens W., Sargan D., Ferguson-Smith M. A. A complete comparative chromosome map for the dog, red fox, and human and its integration with canine genetic maps. Genomics. 1999 Dec 1;62(2):189–202. doi: 10.1006/geno.1999.5989. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES