Professor Jenny Marshall Graves
Distinguished Professor, Professor Emeritus, ANU; Thinker-in-Residence, University of Canberra; Professorial Fellow, University of Melbourne
College of Science, Health and Engineering
School of Life Sciences
Department of Ecology, Environment and Evolution
BS1 room 411, Melbourne (Bundoora)
BSc (Hons), MSc, University of Adelaide; PhD University of California, Berkeley
Membership of professional associations
Fellow, Australian Academy of Science; Royal Society of Victoria; Genetics Society of AustralAsia
Area of study
Jenny Graves made seminal contributions to the understanding of mammalian genome organization and evolution, exploiting the genetic diversity of Australia's unique animals as a source of genetic variation to study highly conserved genetic structures and processes. Her studies of the chromosomes and genes of kangaroos and platypus, devils (Tasmanian) and dragons (lizards) has shed light on the organisation, function and evolution of mammalian genomes, and led to influential new theories of the origin and evolution of human sex chromosomes and sex determining genes. She is (in)famous for her prediction that the human Y chromosome is disappearing. She made critical discoveries that the epigenetic silencing of mammalian X chromosomes occurred by transcriptional inhibition, and is mediated by DNA methylation.
Jenny has been involved in international comparative gene mapping and sequencing projects since the mid-1980s, promulgating the value of comparative genomics and the special value of including distantly related species. She initiated projects to sequence the genomes of marsupials and the platypus, and was Foundation Director of the ARC Centre of Excellence in Kangaroo Genomics.
Jenny received a BSc Hons and MSc from the University of Adelaide for work on the epigenetic silencing of one X chromosome in female marsupials. She then used a Fulbright Travel Grant to do a PhD in molecular biology at the University of California, Berkeley, which she received in 1971 for her work on the control of DNA synthesis in mammalian cells. In 1971, she returned to Australia as a lecturer in Genetics at La Trobe University, becoming a Professor in 1991. In 2001 she moved to the Research School of Biological Sciences, Australian National University as head of the Comparative Genomics Research Unit and Director of the ARC Centre for Excellence in Kangaroo Genomics. She has recently returned to Melbourne as Distinguished Professor at La Trobe University, but also holds honorary positions at ANU, the University of Canberra and the University of Melbourne.
Jenny has published more than 420 scientific works, including 4 books. She was elected a Fellow of the Australian Academy of Science in 1999 and served on the Academy Executive, first as Foreign Secretary, then as Secretary for Education. She is 2006 L’Oreal-UNESCO Laureate, and has received many awards for her work, including the MacFarlane Burnet Medal for research in biology, and an AO.
Jenny taught genetics at La Trobe University at every level for 30 years, making many observations about how students learn to understand how science is done, and trialling many different methods of lecture and practical work. She promotes the idea that every topic in biology is united by evolution, endorsing the maxim that “Nothing in biology makes sense except in the light of evolution.” She is particularly concerned that many students focus on learning science content and never experience the excitement of scientific discovery, being unable to observe and interpret the world for themselves. Through her executive position as Secretary for Education and Public Affairs in the Academy, she promoted inquiry-based ways of teaching primary and highschool science that are engaging to students and engender science literacy in the Australian community.
GRAVES selected recent publications
1. Graves, J.A.M. 2016. Evolution of vertebrate sex chromosomes and dosage compensation. Nature Reviews Genetics, Jan 17 (1) 33-46
2. Koepfli, K.P. et al 2015. The Genome 10K Project and the State of Vertebrate Genomics: A Way Forward. Ann. Rev. Animal Biosci 3: 57-111.
3. Hollely, C.E., O’Meally, D, Sarre, S.D., Graves, J.A.M., Ezaz, T., Matsubara, K., Azad, b., Zhang, X, Georges, A. 2015. Sex reversal triggers the rapid evolution of temperature dependent sex. Nature 523:79-82 (cover story)
4. Georges, A., et al 2015. High-coverage sequencing and annotated assembly of the genome of the Australian dragon lizard Pogona vitticeps. GIGA Science (cover story), 4:45.
5. Graves, J.A.M. 2015. In retrospect: Twenty five years of the sex determining gene. Nature 528: 343-344.
6. Graves, J.A.M. 2014. The epigenetic sole of sex and dosage compensation. Nature Genetics 46, 215–217
7. Bender, H.S., Graves, J.A.M. and Deakin, J.E. 2014. Pathogenesis and molecular biology of a transmissible tumour in the Tasmanian devil. Ann. Rev. Animal Biosciences 2: 165-187
8. Graves, J.A.M., 2014. Avian sex, sex chromosomes and dosage compensation in the age of genomics. Chromosome Research 22: 45-57
9. Graves, J.A.M. 2013. How to evolve new vertebrate sex determining genes. Developmental Dynamics 242: 354-359
10. Graves, J.A.M. and Renfree, M.B. 2013. Marsupials in the age of genomics. Ann Rev. Genomics and Human Genetics 14: 13.1–13.28
11. Deakin, J.E., Delbridge, M.L., Koina, E., Harley, N., Alsop, A.E., Wang, C., Patel, V.S and Graves, J.A.M. 2013. Reconstruction of the ancestral marsupial karyotype from comparative gene maps. BMC Evol Biol. 13:258.
12. Livernois, A., Graves, J.A.M., Waters, P.D. 2012. The origin and evolution of vertebrate sex chromosomes and dosage compensation. Heredity 108: 50-58
13. O’Meally, D., Ezaz, T., Georges, A., Sarre, S.D. and Graves, J.A.M. 2012. Are some chromosomes particularly good at sex? Insights from amniotes. Chromosome Research 20: 7-12
14. Deakin,J.E. et al 2012. Genomic restructuring in the Tasmanian devil facial tumour: chromosome painting and gene mapping provide clues to evolution of a transmissible tumour. PloS Genetics 8, e1002483.
15. Deakin, J.E., Graves, J.A.M. and Rens, W.R. 2012. The evolution of marsupial and monotreme chromosomes. Cytogenetics and Genome Research 137: 113-129
16. Bender, H.S. et al,2012. Extreme telomere length dimorphism in the Tasmanian devil and related marsupials suggests parental control of telomere length. PLoS One 7: e46195.
17. Quinn, A.E., Sarre, S.D., Ezaz, T. and Graves, J.A.M., Georges, A. 2011. Evolutionary transtions between mechanisms of sex determination in vertebrates. Biol. Letters 7:443-448 (cover story)
18. Chaumeil, J., Waters, P.J., Koina, E., Gilbert, C., Robinson, T.J. and Graves, J.A.M. 2011. Evolution from XIST-independent to XIST-controlled X chromosome inactivation: epigenetic modifications in distantly related mammals. PloS One 6 e19040
19. Wang, C. et al, 2011. A second-generation anchored linkage map of the tammar wallaby (Macropus eugenii). BMC Genetics 12: 72.
20. Renfree, M.B et al, 2011. Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development. Genome Biology 12:R81
21. Murtagh, V.J. et al, 2011. Evolutionary history of novel genes on the tammar wallaby Y chromosome: Implications for sex chromosome evolution. Genome Research 22: 498-507. doi:10.1101/gr.120790.111
22. Al Nadaf, S., Deakin, J.E., Gilbert, C., Robinson, T.J., Graves, J.A.M. and Waters, P.D. 2011 A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation. Chromosoma 121: 71-78.DOI 10.1007/s00412-011-0343-8
23. Murchison, E.P. et al, 2010. The Tasmanian Devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer. Science 327: 84-87
24. Graves, J.A.M. 2010. Sex chromosomes and expression of sex-specific genes in the placenta. Placenta 31, Supplement A, Trophoblast Research, 24: S27–S32.
25. Ezaz, T., Sarre, S.D., O’Meally, D., Graves, J.A.M. and Georges, A. 2010. Sex chromosome evolution in lizards: independent origins and rapid transitions. Cytogenet and Genome Res 127: 249-260
26. Graves, J.A.M. and Peichel, C.L. 2010. Are homologies in vertebrate sex determination due to shared ancestry or limited options? Genome Biology 11: 205pp.
27. Al Nadaf, S., Waters, P.D., Koina, E., Deakin, J.E., Jordan, K.S. and Graves, J.A.M. 2010. Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic. Genome Biology 11: R112
28. Patel, V.S., Ezaz, T., Deakin, J.E. and Graves, J.A.M. 2010. Globin gene structure in a reptile supports the transpositional model for amniote a- and b-globin gene evolution. Chromosome Research 18: 897-907
Significant older publications, with explanations of their role
Numbers refer to chronological listing of total publications (attached).
IF=impact factor of journal (number of citations in brackets).
38. Sinclair, A.H., Foster, J.W., Spencer, J.A., Page, D.C., Palmer, M., Goodfellow, P.N. and Graves, J.A.M. 1988. Sequences homologous to ZFY, a candidate human sex-determining gene, are autosomal in marsupials. Nature 336: 780-783 (cover story). IF = 38.6 (citations 180).
First demonstration that the candidate gene ZFY, cloned from the human Y chromosome, is not the mammalian testis determining gene, as had been universally accepted, because it is autosomal in marsupials. This paper triggered a major shift in direction in the field of human sex determination. It also established the value of comparing widely divergent animals to test hypothesis of the mechanisms of basic and highly conserved functions like sex.
87. Foster J.W., Brennan, F.E., Hampikian, G.K., Goodfellow, P.N., Sinclair, A.H., Lovell-Badge, R., Selwood, L., Renfree, M.B., Cooper, D.W. and Graves, J.A.M. 1992. Evolution of sex determination and the Y chromosome: SRY-related sequences in marsupials. Nature 359: 531-533. IF= 38.6 (citations 203)
Discovery that the SRY gene (unlike ZFY) is conserved on the Y chromosome in marsupials as well as placental mammals, and is therefore a good candidate for the mammalian testis determining factor. This gene was subsequently proved to be the “master switch” that controls others in the sex determining pathway in all therian mammals.
117. Foster, J.W. and Graves, J.A.M. 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. IF= 10.5 (citations 265).
Identification of SOX3 as the X-borne partner of SRY, and the SOX gene with sequence most similar to SRY. This led to the highly influential proposal that SOX3 was the ancestor of SRY. This discovery changed the way we look at supposedly “male-specific” genes on the Y, since it implies that even the testis-determining factor evolved from a gene on the X with functions in other tissues. This was the first of several “brains-and-balls” genes on the X that were reshaped on the Y to acquire male-specific functions. With the recent demonstration that ectopic expression of SOX3 in the undifferentiated gonad of XX embryos reverses sex, SOX3 is now a paradigm for how genes may be recruited into new function by a shift in the expression profile.
125. Graves, J.A.M. 1995. The origin and function of the mammalian Y chromosome and Y-borne genes – an evolving understanding. BioEssays 17: 311-320. IF= 5.423 (citations 365)
This highly cited paper put forward the influential hypothesis that the human X and Y both comprise an ancientX region and a region that was recently added to eutherian sex chromosomes.This hypothesis was later confirmed by gene mapping in outgroups such as birds, in which the same two regions are present on autosomes. This widely accepted theory has been used to explain the differences in X inactivation of the old and new regions of the X, as well as to discover the origins of male-specific genes borne on the Y.
144. Delbridge, M.L., Harry, J.L., Toder, R., O’Neill, R.J.W., Ma, K., Chandley, A.C. and Graves, J.A.M. 1997. A human candidate spermatogenesis gene, RBM1, is conserved and amplified on the marsupial Y chromosome. Nature Genetics 15: 131–136 (erratum Nature Genetics 15: 411). IF= 33.1 (citations 122)
Demonstration that the candidate human spermatogenesis gene RBMY is conserved on the Y chromosome in marsupials as well as eutherians. Retention on the Y over the 145 million years since marsupials diverged from placentals means that this gene is likely to have been selected for an important male-specific function. This paper was significant in establishing that comparisons between highly divergent mammals can provide important evidence for gene function in humans.
161. O’Neill, R.J.W., O’Neill, M.J. and Graves, J.A.M. 1998. Undermethylation associated with retroelement activation and chromosome remodelling in an interspecific mammalian hybrid. Nature 393:68-72, erratum Nature 420:106. IF= 38.6 (citations 349)
Here we demonstrated undermethylation, movement and amplification of transposable elements, and de novo chromosome changes in marsupial species hybrids. This implied that genome change in animal species hybrids can be very rapid. The amplified sequence has since been discovered to be an active retroelement, unique in mammals, that accumulates at centromere and facilitates chromosome rearrangements, which we also found to be very frequent in interspecific hybrids. This discovery led to much subsequent work on this element. This paper was of special interest because suggested that repression of DNA methylation might contribute to “genomic shock” in interspecific hybrids.
167. Graves, J.A.M., Wakefield, M.J. and Toder, R. 1998. Evolution of the pseudoautosomal region of mammalian sex chromosomes. Human Molec. Genet. 7: 1991-1996. IF= 7.6 (citations 143)
Here we proposed that the pseudoautosomal region, that is homologous between the human X and Y chromosomes and pairs and recombines during male meiosis, is merely the last vestiges of the autosomal region added to the X and Y early in eutherian radiation. This contradicted the prevailing view that the gene content of the PAR must be significant for its function in meiosis and fertility.
180. Shetty, S., Griffin, D. and Graves, J.A.M. 1999. Comparative chromosome painting reveals strong chromosome homology over 80 million years of bird evolution. Chromosome Research 7: 289–295. IF= 2.8 (citations 203)
We used chromosome painting to show that chicken chromosomes are almost identical to the chromosomes of the emu, a distantly related ratite bird. We went on to show that turtle chromosomes are also virtually identical. This amazing homology was a real shock to the cytogenetic world, used to the great variety of chromosomes in placental mammals. This led me to the hypothesis that vertebrate chromosomes are amazingly stable – with the standout exception of placental mammals..
181. Delbridge, M.L., Lingenfelter, P.A., Disteche, C.M. and Graves, J.A.M. 1999. The candidate spermatogenesis gene RBMY has a homologue on the human X chromosome. Nature Genetics 22: 223–224. IF= 33.1 (citations 135)
We discoved an X chromosome borne copy of the spermatogenesis gene RBMY on the Y. we proposed that RBMX was the ancestor of RBMY. This was particularly significant because RBMY was proposed to be a “Class II male-specific gene” that did not have an X origin. The paper lead to a (reluctant) recognition that most genes on the human Y chromosome have partners on the X from which they diverged, and that these represent ancient genes that exist in autosomal syntenic blocks in other vertebrates. RBMX has since been found to have critical functions in neural development.
184. O’Brien, S.J., Menotti-Raymond, M., Murphy, W.J., Nash, W.G., Wienberg, J., Stanyon, R., Copeland, N.G., Jenkins, N.A., Womack, J.E. and Graves, J.A.M. 1999. The promise of comparative genomics in mammals. Science 286: 458-481 (cover story). IF= 32.5 (citations 527)
This highly cited review was a call to arms to take comparative genomics seriously in evaluating human gene arrangement and genome sequence. It has been very influential in heightening the impact of comparative genomics.
260. Grützner, F., Rens, W., Tsend-Ayush, E., El-Mogharbel, N., O’Brien, P.C.M., Jones, R.C., Ferguson-Smith, M.A. and Graves, J.A.M. 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. IF= 38.6 (citations 205)
We discovered that at male meiosis the ten platypus sex chromosomes are arranged in a multivalent translocation chain and segregate alternately to produce two kinds of sperm, 5X (female-determining) and 5Y (male-determining). Although this extraordinary system is remarkably efficient (we never saw sperm with mixtures of X and Y chromosomes), what could have led to the evolution of such a bizarre system has been the topic of much speculation; this paper seems to have topped the charts for weird papers to give graduate students to discuss. Its featuring on the website of the Discovery Institute in Seattle as an example of “Intelligent Design” was the inspiration behind my instigation of a “Dumb Design” website set up through the Australian Academy of Science.
261. Rens, W., Grützner, F., O’Brien, P.C.M., Fairclough, H., Graves, J.A.M. and Ferguson-Smith, M.A. 2004. Resolution and evolution of the duck-billed platypus karyotype with an X1Y1 X2Y2 X3Y3 X4Y4 X5Y5 male sex chromosome constitution. Proc. Natl Acad Sci US 101: 16257-16261. IF= 10.5 (citations 129)
We discovered that the platypus has ten sex chromosomes; five X chromosomes (present in two copies in females and one in males) and 5 Y chromosomes (specific to males). All the Xs (and Ys) are genetically different. Platypus sex chromosomes had been the source of great speculation for 20 years, and we were able to resolve the system using chromosome paints.
288. Graves, J.A.M. 2006. Sex chromosome specialization and degeneration in mammals. Cell 124: 901-914. IF= 34.4 (citations 362)
This highly cited review details my hypothesis that the mammalian Y (including human) represents a degraded X, and the genes it bears are mostly relics of genes on the X. I proposed that the Y is likely to disappear and be replaced in 10 million years (recently revised to 4.6 million years in the light of our evidence for the recent origin of human sex chromosomes). I presented alternative models for the kinetics of degradation. This proposal has caused unwonted interest (and hostility) and sparked many challenges and debates, but its basic premise that the mammalian Y chromosome is degrading (and has even disappeared in some rodent lineages) is now widely accepted, and there are now serious attempts to define and predict the kinetics of loss, and to predict what happens to human sex determination, and even hominid speciation, after the loss of the human Y chromosome.
313. Quinn, A.E., Georges, A., Sarre, S., Guarino, F., Ezaz, T. and Graves, J.A.M. 2007. Temperature sex reversal implies sex gene dosage in a reptile. Science 316: 411. IF= 32.5 (citations 120)
Some reptiles have chromosome-based sex determination, and others (such as alligator) have temperature dependent sex. Remarkably, we discovered that the Australian Dragon lizard has both. We identified Z and W sex chromosomes (ZZ male and ZW female, like birds), but found that at high temperature ZZ as well as ZW eggs all hatch into females. This extraordinary result shows that environmental and genetic modes of sex determination are not qualitatively different, as had been thought for decades, but interact in reptiles. I proposed that sex in this species is determined by a dosage-sensitive product of a gene on the Z chromosome that is inactivated at high temperatures. This was the first success in a now very extensive “Sex in Dragons” project, in which we have sequenced the entire genome and produced novel candidate genes for sex determination.
314. Mikkelsen, T.S., Wakefield, M.J. …(150 authors) …Graves, J.A.M., Ponting, C.P. Breen, M., Samollow, P.B., Lander, E.S. and Lindblad-Toh, K. 2007. Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences. Nature 447: 177 (cover story). IF= 38.6 (citations 491)
The opossum was first marsupial to be subjected to full genome sequencing. It is important because marsupials are very distantly related to humans and other placental mammals (more than twice the genetic divergence of mice and humans). Amongst many new insights, we showed that the gene set is similar but the repetitive fraction is very different, revealing that transposable elements have been exapted into roles in genetic control. This paper sparked many companion papers, as well as completion of the kangaroo genome, published recently as a whole issue of Genome Biology.
333. Warren, W.C., Hillier, L.W., Graves, J.A.M. et al (100 authors) 2008. Genome analysis of the platypus reveals unique signatures of evolution. Nature 453:175-183 (cover story). IF= 38.6 (citations 503)
The duckbilled platypus, although it is a mammal, retains many reptilian features, and diverged from therians (marsupials and placentals) 166 million years ago. The genome sequence of the platypus was therefore eagerly awaited because it provided an outgroup for the understanding of the function and evolution of genomes of all other mammals, and a bridge to the genomes of reptiles. The genome proved to be as remarkable as these curious mammals, revealing a mix of typical mammal genes (eg milk) and genes of birds (eg egg yolk) and reptiles (eg venom peptides).
342. Veyrunes, F., Waters, P.D., Miethke, P., Rens, W., McMillan, D., Alsop, A.E., Grützner, F., Deakin, J.E., Whittington, C.M., Schatzkamer, K., Kremitzky, C.L., Graves, T., Ferguson-Smith, M.A., Warren, W. and Graves, J.A.M. 2008. Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes. Genome Research 18: 965-973 (cover story). IF= 13.6 (citations 204)
Here we report our mind-boggling discovery that the sex chromosomes of the platypus are unrelated to the X and Y of placental and marsupial mammals, but have homology to bird sex chromosomes. The two genome regions that form the mammal XY pair are both autosomal in platypus. This completely changed our understanding of how and when mammal sex chromosomes evolved. Since they were still autosomes when monotremes diverged from therian mammals 166 million years ago, the mammal XY (and the SRY gene) must be younger than this date, rather than the previously accepted 310 million years since mammals diverged from reptiles. This paper engendered many companion papers and cemented the reputation of “weird mammals” to deliver unexpected insights into the function and evolution of very basic and conserved genetic systems in all mammals.
Current projects I am involved in include:
• Sequencing the genome of the dragon lizard in order to discover the genes on Z or W chromosomes that determine sex, and genes in the sex determining pathway that are influenced by temperature.
• Sequencing the genome of the echidna to discover how monotreme sex chromosomes (homologous to bird, not mammal sex chromosomes) evolved and how they work.
• Evolution of epigenetic silencing mechanisms in mammals.