Incomplete transcriptional dosage compensation of chicken and platypus sex chromosomes is balanced by post-transcriptional compensation

Author:

Lister Nicholas C.1ORCID,Milton Ashley M.1ORCID,Patel Hardip R.23ORCID,Waters Shafagh A.4ORCID,Hanrahan Benjamin J.1,McIntyre Kim L.1,Livernois Alexandra M.5,Horspool William B.1,Wee Lee Kian1,Ringel Alessa R.678,Mundlos Stefan679,Robson Michael I.6710,Shearwin-Whyatt Linda11,Grützner Frank11ORCID,Graves Jennifer A. Marshall1213ORCID,Ruiz-Herrera Aurora1415ORCID,Waters Paul D.1ORCID

Affiliation:

1. School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales Sydney, Sydney, NSW 2052, Australia

2. John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia

3. National Centre for Indigenous Genomics, Australian National University, Canberra, ACT 2600, Australia

4. School of Biomedical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW 2052, Australia

5. Zymeworks, Vancouver, BC V5T 1G4, Canada

6. Max Planck Institute for Molecular Genetics, Berlin 14195, Germany

7. Institute for Medical and Human Genetics, Charité Universitätsmedizin Berlin, Berlin 10117, Germany

8. Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin 14195, Germany

9. Charité-Universitätsmedizin Berlin, Berlin Institute of Health Center for Regenerative Therapies, Berlin 13353, Germany

10. Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH8 9YL, United Kingdom

11. School of Biological Sciences, University of Adelaide, Adelaide, SA 5000, Australia

12. Department of Environment and Genetics, La Trobe University, Melbourne, VIC 3068, Australia

13. Institute of Applied Ecology, University of Canberra, Canberra, ACT 2601, Australia

14. Departament de Biologia Cellular, Fisiologia I Immunologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Spain

15. Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Spain

Abstract

Heteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between sexes and with autosomes. A need for dosage compensation has long been thought to be critical in vertebrates. However, this was questioned by findings of unequal mRNA abundance measurements in monotreme mammals and birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females and a correlation with differential loading of histone modifications. We also observed unbalanced transcripts of Z genes in chicken. Surprisingly, however, we found that protein abundance ratios were 1:1 between the sexes in both species, indicating a post-transcriptional layer of dosage compensation. We conclude that sex chromosome output is maintained in chicken and platypus (and perhaps many other non therian vertebrates) via a combination of transcriptional and post-transcriptional control, consistent with a critical importance of sex chromosome dosage compensation.

Funder

Department of Education and Training | Australian Research Council

Publisher

Proceedings of the National Academy of Sciences

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