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Elephant Shark Genome Provides New Insights into Bone Formation and Adaptive Immunity in Humans

Source: A*STAR


A*STAR-led international consortium completely decodes the first shark-family
member genome


Singapore, Jan 9, 2014 - (ACN Newswire) - Scientists at A*STAR's Institute of Molecular and Cell Biology (IMCB) led an international team of researchers that sequenced and analysed the genome of the elephant shark. A comparison of the elephant shark genome with human and other vertebrate genomes revealed why the skeleton of sharks consists entirely of cartilage instead of bones. The findings carry potential implications for human bone disease treatment. The analysis also sheds new light on the origin of the adaptive immune system. The findings of this study are published in the 9 January, 2014 issue of the prestigious scientific journal, Nature.

The collaboration with 12 international institutions(1) was headed by IMCB's Prof Byrappa Venkatesh, who is also a chairperson of the "Genome10K" Project. The project was largely funded by the National Institutes of Health (NIH), USA, the world's foremost centre for the support of biomedical research.

Analysis of the elephant shark genome

Elephant shark is a member of cartilaginous fishes, which are the oldest living group of jawed vertebrates that diverged from bony vertebrates about 450 million years ago. Cartilaginous fishes include sharks, rays, skates and chimaeras. Unlike humans and other bony vertebrates, cartilaginous fishes are unable to replace cartilage with bone. Among over 1,200 species of cartilaginous fishes, the elephant shark was sequenced due to its compact genome size. Analysis of the elephant shark genome identified a family of genes absent in elephant shark but present in all bony vertebrates. A significant reduction in bone formation was observed when a member of this gene family was knocked out in zebrafish, thereby indicating the importance of this gene family in bone formation. The finding has important implications towards our understanding of bone-related diseases such as osteoporosis and hence the development of effective therapeutic strategies for them.

An unexpected finding was that elephant shark appears to lack special types of immune cells previously considered essential for defence against viral/bacterial infections and preventing autoimmune reactions such as diabetes and rheumatoid arthritis(2). Despite this seemingly primitive organization of the immune system, sharks exhibit robust immune defences and are long-lived. By challenging long-held notions, this discovery has opened up a new avenue towards the development of nonintuitive strategies to shape the immune functions of humans.

The study also found that the elephant shark genome is the slowest evolving among all vertebrates, including the coelacanth, popularly known as a "living fossil", whose genes were recently shown to be evolving slower than those of other bony vertebrates(3). Furthermore, large blocks of elephant shark and human chromosomes were found to be highly similar. The markedly slow evolution of the elephant shark genome and its similarity to the human genome, further underscores its importance as a reference genome for comparative genomic studies aimed at better understanding of the human genome.

Prof Byrappa Venkatesh, Research Director at IMCB, and lead author of the Nature paper added, "The slow evolving genome of the elephant shark is probably the best proxy for the ancestor of all jawed-vertebrates that became extinct a long time ago. It is a cornerstone for improving our understanding of the development and physiology of human and other vertebrates as illustrated by our analysis of the skeletal system and immune system genes."

Dr Wes Warren, senior author of the Nature paper commented, "Although cartilaginous vertebrates and bony vertebrates diverged about 450 million years ago, with the elephant shark genome in hand, we can now begin to identify key genetic adaptations in the evolutionary tree."

Prof Hong Wanjin, Executive Director of IMCB, said, "Over the years, IMCB has carried out several remarkable genomic projects and we are excited to showcase yet another milestone. Not only has our research team sequenced the first shark-family member genome, they have also uncovered many insights significant to the field of genomic and medical research through the genome analysis."

Prof Sir David Lane, Chief Scientist at A*STAR, said, "We are delighted that a Singapore laboratory conceived and led a major international genome project. The international research grant from NIH, USA is a testimony of Singapore's world-class standard in genomics research."

(1) 1) Institute of Molecular and Cell Biology, A*STAR, Singapore; 2) Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 3) Max-Planck-Institute of Immunobiology and Epigenetics, Germany; 4) University of Maryland, Baltimore, USA; 5) Hokkaido University Graduate School of Medicine, Japan; 6) Molecular Engineering Laboratory, A*STAR, Singapore; 7) San Francisco State University, San Francisco, USA; 8) Banting and Best Department of Medical Research and Donnelly Centre, University of Toronto, Canada; 9) Institut de Biologia Evolutiva, Barcelona, Spain; 10) Institucio Catalana de Recerca i Estudis Avancats, Barcelona, Spain; 11) Center for Biomolecular Science and Engineering, School of Engineering, University of California Santa Cruz, USA; 12) The Genome Institute at Washington University, St. Louis, USA.
(2) Rheumatoid arthritis is an autoimmune disease which results in a chronic, systemic inflammatory disorder that may affect many tissues and organs.
(3) Amemiya, CT. et al. 2013 The African coelacanth genome provides insights into tetrapod evolution. Nature 496: 311-316.

Notes for Editor:

The research findings described in this media release can be found in the 9 January, 2014 issue of Nature Journal, under the title, "Elephant shark genome provides unique insights into gnathostome evolution" by Byrappa Venkatesh,1,2, Alison P. Lee,1, Vydianathan Ravi,1, Ashish K. Maurya,3, Michelle M. Lian,1, Jeremy B. Swann,4, Yuko Ohta,5, Martin F. Flajnik,5, Yoichi Sutoh,6, Masanori Kasahara,6, Shawn Hoon,7, Vamshidhar Gangu,7, Scott W. Roy,8, Manuel Irimia,9, Vladimir Korzh,10, Igor Kondrychyn,10, Zhi Wei Lim,1, Boon-Hui Tay,1, Sumanty Tohari,1, Kiat Whye Kong,7, Shufen Ho,7, Belen Lorente-Galdos,11,12, Javier Quilez,11,12, Tomas Marques-Bonet,11,12, Brian J. Raney,13, Philip W. Ingham,3, Alice Tay,1, LaDeana W. Hillier,14, Patrick Minx,14, Thomas Boehm,4, Richard K. Wilson,14, Sydney Brenner,1 & Wesley C. Warren,14.

1. Comparative Genomics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
2. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
3. Developmental and Biomedical Genetics Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
4. Department of Developmental Immunology, Max-Planck-Institute of Immunobiology
and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
5. Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201 USA.
6. Department of Pathology, Hokkaido University Graduate School of Medicine,
Sapporo 060-8638, Japan.
7. Molecular Engineering Laboratory, Biomedical Sciences Institutes, A*STAR,
Biopolis, Singapore 138673.
8. Department of Biology, San Francisco State University, San Francisco, CA 94132, USA.
9. Banting and Best Department of Medical Research and Donnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
10. Fish Developmental Biology Laboratory, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
11. Institut de Biologia Evolutiva, (UPF-CSIC), PRBB, 08003 Barcelona, Spain.
12. Institucio Catalana de Recerca i Estudis Avancats (ICREA), 08010 Barcelona,
Catalonia, Spain.
13. Center for Biomolecular Science and Engineering, School of Engineering,
University of California Santa Cruz, Santa Cruz, CA 95064, USA.
14. The Genome Institute at Washington University, St. Louis, MO 63108, USA.

Correspondence should be addressed to Byrappa Venkatesh ([email protected])

Full text of the article can be accessed from
http://www.nature.com/nature/journal/v505/n7482/index.html.

For more information about the elephant shark genome, please visit:
http://esharkgenome.imcb.a-star.edu.sg.

About Institute of Molecular and Cell Biology (IMCB)

The Institute of Molecular and Cell Biology (IMCB) was established in 1987 at the National University of Singapore (NUS) before becoming an autonomous research institute (RI) of A*STAR and moving to Biopolis in 2004. IMCB strives to maintain the scientific excellence of PI-driven research and at the same time aims to promote collaborative team-based projects of medical and industrial relevance.

Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB's
research activities focus on four major fields: Animal Models of Development and
Disease, Cancer Genetics and Therapeutics, Cell Biology in Health and Disease,
and Structural Biology and Drug Discovery. For more information about IMCB, please visit www.imcb.a-star.edu.sg.

About A*STAR

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy. In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry. A*STAR oversees 20 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis as well as their vicinity. These two R&D hubs, house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories. For more information about A*STAR, please visit www.a-star.edu.sg.

Source: A*STAR

Contact:
Tan Yun Yun (Ms)
Senior Officer, Corporate Communications
Agency for Science, Technology and Research
Tel: +65 6826 6273
Email: [email protected]




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