Skip to main content
SpringerLink
Log in

Enrichment of brain-related genes on the mammalian X chromosome is ancient and predates the divergence of synapsid and sauropsid lineages

  • Published:
Chromosome Research Aims and scope Submit manuscript

Abstract

Previous studies have revealed an enrichment of reproduction- and brain-related genes on the human X chromosome. In the present study, we investigated the evolutionary history that underlies this functional specialization. To do so, we analyzed the orthologous building blocks of the mammalian X chromosome in the chicken genome. We used Affymetrix chicken genome microarrays to determine tissue-selective gene expression in several tissues of the chicken, including testis and brain. Subsequently, chromosomal distribution of genes with tissue-selective expression was determined. These analyzes provided several new findings. Firstly, they showed that chicken chromosomes orthologous to the mammalian X chromosome exhibited an increased concentration of genes expressed selectively in brain. More specifically, the highest concentration of brain-selectively expressed genes was found on chicken chromosome GGA12, which shows orthology to the X chromosomal regions with the highest enrichment of non-syndromic X-linked mental retardation (MRX) genes. Secondly, and in contrast to the first finding, no enrichment of testis-selective genes could be detected on these chicken chromosomes. These findings indicate that the accumulation of brain-related genes on the prospective mammalian X chromosome antedates the divergence of sauropsid and synapsid lineages 315 million years ago, whereas the accumulation of testis-related genes on the mammalian X chromosome is more recent and due to adaptational changes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

My:

million years

Mya:

million years ago

XAR:

X added region

XCR:

X conserved region

References

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 36:289–300

    Google Scholar 

  • Bininda-Emonds OR, Cardillo M, Jones KE et al (2007) The delayed rise of present-day mammals. Nature 446:507–512

    Article  PubMed  CAS  Google Scholar 

  • Chelly J, Mandel JL (2001) Monogenic causes of X-linked mental retardation. Nat Rev Genet 2:669–680

    Article  PubMed  CAS  Google Scholar 

  • Consortium ICGS (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432:695–716

    Article  Google Scholar 

  • Delbridge ML, Patel HR, Waters PD, McMillan DA, Graves JA (2009) Does the human X contain a third evolutionary block? Origin of genes on human Xp11 and Xq28. Genome Res 19(8):1350–1360

    Article  PubMed  CAS  Google Scholar 

  • Ellegren H (2008) Sex chromosomes: platypus genome suggests a recent origin for the human X. Curr Biol 18:R557–R559

    Article  PubMed  CAS  Google Scholar 

  • Ellegren H, Fridolfsson AK (1997) Male-driven evolution of DNA sequences in birds. Nat Genet 17:182–184

    Article  PubMed  CAS  Google Scholar 

  • Emerson JJ, Kaessmann H, Betran E, Long M (2004) Extensive gene traffic on the mammalian X chromosome. Science 303:537–540

    Article  PubMed  CAS  Google Scholar 

  • Foster JW, Graves JA (1994) An SRY-related sequence on the marsupial X chromosome: implications for the evolution of the mammalian testis-determining gene. Proc Natl Acad Sci U S A 91:1927–1931

    Article  PubMed  CAS  Google Scholar 

  • Fraser P, Bickmore W (2007) Nuclear organization of the genome and the potential for gene regulation. Nature 447:413–417

    Article  PubMed  CAS  Google Scholar 

  • Glas R, Marshall Graves JA, Toder R, Ferguson-Smith M, O’Brien PC (1999) Cross-species chromosome painting between human and marsupial directly demonstrates the ancient region of the mammalian X. Mamm Genome 10:1115–1116

    Article  PubMed  CAS  Google Scholar 

  • Graves JA (1995) The evolution of mammalian sex chromosomes and the origin of sex determining genes. Philos Trans R Soc Lond B Biol Sci 350:305–311 discussion 311–302

    Article  PubMed  CAS  Google Scholar 

  • Graves JA, Gecz J, Hameister H (2002) Evolution of the human X—a smart and sexy chromosome that controls speciation and development. Cytogenet Genome Res 99:141–145

    Article  PubMed  CAS  Google Scholar 

  • Grutzner F, Rens W, Tsend-Ayush E et al (2004) In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes. Nature 432:913–917

    Article  PubMed  Google Scholar 

  • Hsiao LL, Dangond F, Yoshida T et al (2001) A compendium of gene expression in normal human tissues. Physiol Genomics 7:97–104

    PubMed  CAS  Google Scholar 

  • Hurst LD, Randerson JP (1999) An eXceptional chromosome. Trends Genet 15:383–385

    Article  PubMed  CAS  Google Scholar 

  • Kaiser VB, Ellegren H (2006) Nonrandom distribution of genes with sex-biased expression in the chicken genome. Evolution 60:1945–1951

    PubMed  CAS  Google Scholar 

  • Khaitovich P, Muetzel B, She X et al (2004) Regional patterns of gene expression in human and chimpanzee brains. Genome Res 14:1462–1473

    Article  PubMed  CAS  Google Scholar 

  • Kohn M, Kehrer-Sawatzki H, Vogel W, Graves JA, Hameister H (2004) Wide genome comparisons reveal the origins of the human X chromosome. Trends Genet 20:598–603

    Article  PubMed  CAS  Google Scholar 

  • Kohn M, Hogel J, Vogel W et al (2006) Reconstruction of a 450-My-old ancestral vertebrate protokaryotype. Trends Genet 22:203–210

    Article  PubMed  CAS  Google Scholar 

  • Lahn BT, Page DC (1999) Four evolutionary strata on the human X chromosome. Science 286:964–967

    Article  PubMed  CAS  Google Scholar 

  • LaVail JH, Cowan WM (1971) The development of the chick optic tectum. I. Normal morphology and cytoarchitectonic development. Brain Res 28:391–419

    CAS  Google Scholar 

  • Lehrke RG (1974) X-linked mental retardation and verbal disability. Birth Defects Orig Artic Ser 10:1–100

    PubMed  CAS  Google Scholar 

  • Lubs H, Chiurazzi P, Arena J, Schwartz C, Tranebjaerg L, Neri G (1999) XLMR genes: update 1998. Am J Med Genet 83:237–247

    Article  PubMed  CAS  Google Scholar 

  • Mateos-Langerak J, Goetze S, Leonhardt H, Cremer T, van Driel R, Lanctot C (2007) Nuclear architecture: is it important for genome function and can we prove it? J Cell Biochem 102:1067–1075

    Article  PubMed  CAS  Google Scholar 

  • Nanda I, Zend-Ajusch E, Shan Z et al (2000) Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination. Cytogenet Cell Genet 89:67–78

    Article  PubMed  CAS  Google Scholar 

  • Nielsen R, Bustamante C, Clark AG et al (2005) A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol 3:e170

    Article  PubMed  Google Scholar 

  • Ropers HH, Hamel BC (2005) X-linked mental retardation. Nat Rev Genet 6:46–57

    Article  PubMed  CAS  Google Scholar 

  • Ropers HH, Hoeltzenbein M, Kalscheuer V et al (2003) Nonsyndromic X-linked mental retardation: where are the missing mutations? Trends Genet 19:316–320

    Article  PubMed  CAS  Google Scholar 

  • Saifi GM, Chandra HS (1999) An apparent excess of sex- and reproduction-related genes on the human X chromosome. Proc Biol Sci 266:203–209

    Article  PubMed  CAS  Google Scholar 

  • Simonis M, Klous P, Splinter E et al (2006) Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nat Genet 38:1348–1354

    Article  PubMed  CAS  Google Scholar 

  • Storchova R, Divina P (2006) Nonrandom representation of sex-biased genes on chicken Z chromosome. J Mol Evol 63:676–681

    Article  PubMed  CAS  Google Scholar 

  • Storey JD, Tibshirani R (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 100:9440–9445

    Article  PubMed  CAS  Google Scholar 

  • Vallender EJ, Lahn BT (2004) How mammalian sex chromosomes acquired their peculiar gene content. Bioessays 26:159–169

    Article  PubMed  CAS  Google Scholar 

  • Veyrunes F, Waters PD, Miethke P et al (2008) Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes. Genome Res 18:965–973

    Article  PubMed  CAS  Google Scholar 

  • Voolstra C, Tautz D, Farbrother P, Eichinger L, Harr B (2007) Contrasting evolution of expression differences in the testis between species and subspecies of the house mouse. Genome Res 17:42–49

    Article  PubMed  CAS  Google Scholar 

  • Wallis MC, Waters PD, Delbridge ML et al (2007) Sex determination in platypus and echidna: autosomal location of SOX3 confirms the absence of SRY from monotremes. Chromosome Res 15:949–959

    Article  PubMed  CAS  Google Scholar 

  • Waters PD, Duffy B, Frost CJ, Delbridge ML, Graves JA (2001) The human Y chromosome derives largely from a single autosomal region added to the sex chromosomes 80–130 million years ago. Cytogenet Cell Genet 92:74–79

    Article  PubMed  CAS  Google Scholar 

  • Wilcox SA, Watson JM, Spencer JA, Graves JA (1996) Comparative mapping identifies the fusion point of an ancient mammalian X-autosomal rearrangement. Genomics 35:66–70

    Article  PubMed  CAS  Google Scholar 

  • Wurtele H, Chartrand P (2006) Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended Chromosome Conformation Capture methodology. Chromosome Res 14:477–495

    Article  PubMed  Google Scholar 

  • Wyckoff GJ, Wang W, Wu CI (2000) Rapid evolution of male reproductive genes in the descent of man. Nature 403:304–309

    Article  PubMed  CAS  Google Scholar 

  • Zechner U, Wilda M, Kehrer-Sawatzki H, Vogel W, Fundele R, Hameister H (2001) A high density of X-linked genes for general cognitive ability: a run-away process shaping human evolution? Trends Genet 17:697–701

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This work was supported by the Deutsche Forschungsgemeinschaft (Ha 1082/16-4) and by Vetenskapsrådet (RF).

Author information

Author notes

  1. Horst Hameister

    Present address: Genetikum, Neu-Ulm, Germany

  2. Claus Kemkemer

    Present address: Section of Evolutionary Biology, LMU BioCenter, Planegg-Martinsried, Germany

Authors and Affiliations

  1. Institute of Human Genetics, University of Ulm, Ulm, Germany

    Claus Kemkemer, Matthias Kohn, Hildegard Kehrer-Sawatzki & Horst Hameister

  2. Sub-department of Animal Development and Genetics, Evolutionary Biology Center, Uppsala University, Norbyvägen 18A, 75236, Uppsala, Sweden

    Reinald H. Fundele

Authors
  1. Claus Kemkemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias Kohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hildegard Kehrer-Sawatzki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reinald H. Fundele
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Horst Hameister
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Reinald H. Fundele.

Additional information

Responsible Editor: Hans-Joachim Lipps.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table S1

Transcripts selected for the control of gene expression by semi-quantitative PCR. (DOC 32 kb)

Supplementary Table S2

Primer pairs for the amplification of the five transcripts. (DOC 34 kb)

Supplementary Table S3

Distribution of brain-selective genes on GGA chromosome 4 regions (DOC 54 kb)

Supplementary Figure S1

Liver specific expression. (DOC 255 kb)

Supplementary Figure S2

Heart specific expression (DOC 284 kb)

Supplementary Figure S3

Lobe specific expression. (DOC 97 kb)

Supplementary Figure S4

Testis specific expression. (DOC 299 kb)

Supplementary Figure S5

Comparison heart/lobe: The upper figure shows a MA-Plot and the lower figure a Volcano-Plot. Blue and the violet data points show higher expression in the lobe and the red and green data points show a higher expression in the heart. The two colour transition indicates the transition at a threshold of FC 1. (DOC 104 kb)

Supplementary Figure S6

Comparison heart/testis: The upper figure shows a MA-Plot and the lower figure a Volcano-Plot. Blue and the violet data points show higher expression in the testis and the red and green data points show a higher expression in the heart. The two colour transition indicates the transition at a threshold of FC 1. (DOC 118 kb)

Supplementary Figure S7

Comparison liver/heart: The upper figure shows a MA-Plot and the lower figure a Volcano-Plot. Blue and the violet data points show higher expression in the heart and the red and green data points show a higher expression in the liver. The two colour transition indicates the transition at a threshold of FC 1. (DOC 106 kb)

Supplementary Figure S8

Comparison liver/lobe: The upper figure shows a MA-Plot and the lower figure a Volcano-Plot. Blue and the violet data points show higher expression in the lobe and the red and green data points show a higher expression in the liver. The two colour transition indicates the transition at a threshold of FC 1. (DOC 109 kb)

Supplementary Figure S9

Comparison liver/testis: The upper figure shows a MA-Plot and the lower figure a Volcano-Plot. Blue and the violet data points show higher expression in the testis and the red and green data points show a higher expression in the liver. The two colour transition indicates the transition at a threshold of FC 1. (DOC 116 kb)

Supplementary Figure S10

Comparison lobe/testis: The upper figure shows a MA-Plot and the lower figure a Volcano-Plot. Blue and the violet data points show higher expression in the testis and the red and green data points show a higher expression in the lobe. The two colour transition indicates the transition at a threshold of FC 1. (DOC 118 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kemkemer, C., Kohn, M., Kehrer-Sawatzki, H. et al. Enrichment of brain-related genes on the mammalian X chromosome is ancient and predates the divergence of synapsid and sauropsid lineages. Chromosome Res 17, 811–820 (2009). https://doi.org/10.1007/s10577-009-9072-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10577-009-9072-8

Keywords

Search

Navigation