Nav: Home

Gene enhancer in evolution of human opposable thumb

September 04, 2008

Scientists have discovered a gene enhancer, known as HACNS1, that may have contributed to the evolution of the uniquely opposable human thumb, and possibly also modifications in the ankle or foot that allow humans to walk on two legs, according to a paper published in Science on Sept. 5, 2008.

This study is the first to provide evidence of the existence of human-specific gene enhancers, which are switches near genes in the human genome.

Dr. Shyam Prabhakar, first author of the paper and Senior Research Scientist at the Genome Institute of Singapore (GIS), said, "Opposable thumbs, manual dexterity and ankle or foot adaptations for walking on two legs are hallmarks of our species. We think we may have discovered one of the pieces of the genome that encodes some of these definitive human traits.

"This is just the first step - we need to characterize HACNS1 in more detail, and also test the hundreds of other HACNSs we have identified in the genome to figure out what role, if any, they play in making us human," he added.

The opposability of the human thumb is its unique ability to swing toward the palm and oppose the other four fingers to provide a tighter and more precise grip on objects.

The surprising complexity and abundance of enhancers, which turn on genes in the appropriate cells, have only recently been appreciated. Evolutionary changes in the DNA sequence of enhancers are thought to have triggered changes in human development that make us different from chimpanzees and other apes. Thus, the many observable differences between humans and chimpanzees, such as brain size, hair density, tooth patterns, pelvic structure and hand and foot modifications, could have arisen partly through changes in the way developmental genes are turned on.

The discovery provides significant insights into the genetic differences between humans and chimpanzees - the species that is approximately 99 percent similar to humans in terms of genetic composition. Apart from the obvious evolutionary interest, a more practical goal of such research is a more complete molecular understanding of the human body, leading eventually to a better understanding of human diseases and their treatments.

On a hunt for enhancers that could make us human, the authors of this study zoomed in on a genomic region they termed human-accelerated conserved non-coding sequence 1 (HACNS1).

HACNS1 showed statistical signatures of being an enhancer, and also had the most surprising amount of sequence change during human evolution of all the 110,000 such sequences identified in the human genome - it was by far the most striking candidate.

Remarkably, HACNS1 was found to play a unique human-specific gene-activating role in a region of the developing limb that eventually forms the junction of the wrist and thumb, and also extends partially into the developing thumb. A similar, though weaker activating role was also observed in the corresponding ankle/foot-forming regions of the developing hind limbs.

Highlighting the practical long-term goal of their joint project, Dr. James P. Noonan, last author and Assistant Professor at Yale University, pointed out, "Insights into human diseases and their treatments are often obtained through studies in non-human 'model organisms' such as mice. However, many human diseases are not reproducible in mice, and some diseases such as Alzheimer's and HIV/AIDS are not even known to exist in chimpanzees, our closest 'relatives'. Moreover, even if a disease is observable in a model organism, inter-species differences often cause treatments that appear to work when tested on, say, lab mice, to fail at the stage of human clinical trials. It is therefore imperative for human medicine that we fill in the gaps between our species and others by comprehensively characterizing human-specific genomic sequences and molecular processes. For this reason, it is important that we understand, at a molecular level, what it means to be human."

Principal Investigator at Singapore's Institute of Molecular and Cell Biology (IMCB), Associate Professor Venkatesh Byrappa added, "This is an elegant demonstration that changes in the gene regulatory region have actually led to a novel function unique to humans. These changes might be associated with morphological innovations that distinguish humans from other primates."
The study, led by Drs Prabhakar and Noonan, was initiated in Dr Edward M. Rubin's lab at the Lawrence Berkeley National Laboratory (LBNL) and continued as collaboration between the three groups (Noonan, Prabhakar, and Rubin).

Notes to editor:

Research publication: The research findings are reported in the Sept. 4, 2008 issue of Science in a paper titled, "Human-Specific Gain of Function in a Developmental Enhancer".

Authors: Shyam Prabhakar,1* Axel Visel,1 Jennifer A. Akiyama,1 Malak Shoukry,1 Keith D. Lewis,1† Amy Holt,1 Ingrid Plajzer-Frick,1 Harris Morrison,2 David R. FitzPatrick,2 Veena Afzal,1 Len A. Pennacchio,1,3 Edward M. Rubin,1,3 James P. Noonan1§

1. Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
2. MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
3. United States Department of Energy Joint Genome Institute, Walnut Creek, CA 94598, USA.

*Present address: Computational and Mathematical Biology, Genome Institute of Singapore 138672, Singapore.
†Present address: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
§Present address: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.

Genome Institute of Singapore (GIS)

GIS is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, GIS pursues the integration of technology, genetics and biology towards the goal of individualized medicine. GIS' key research areas include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

Agency for Science, Technology and Research (A*STAR)

A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 14 research institutes and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. A*STAR also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority the agency places on nurturing the next generation of scientific talent.

For enquiries, please contact the following:
Genome Institute of Singapore
Winnie Serah Lim
Corporate Communications
Tel: (65) 6478 8013
(65) 9730 7884

Agency for Science, Technology and Research (A*STAR), Singapore

Related Evolution Articles:

Prebiotic evolution: Hairpins help each other out
The evolution of cells and organisms is thought to have been preceded by a phase in which informational molecules like DNA could be replicated selectively.
How to be a winner in the game of evolution
A new study by University of Arizona biologists helps explain why different groups of animals differ dramatically in their number of species, and how this is related to differences in their body forms and ways of life.
The galloping evolution in seahorses
A genome project, comprising six evolutionary biologists from Professor Axel Meyer's research team from Konstanz and researchers from China and Singapore, sequenced and analyzed the genome of the tiger tail seahorse.
Fast evolution affects everyone, everywhere
Rapid evolution of other species happens all around us all the time -- and many of the most extreme examples are associated with human influences.
Landscape evolution and hazards
Landscapes are formed by a combination of uplift and erosion.
More Evolution News and Evolution Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...