Gene enhancer in evolution of human opposable thumb

September 05, 2008

Reported in Sept. 5, 2008, Science

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."

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

---

---

	Opposable Thumb by Jason B. Reed Evil is unleashed! An escapade in search of adventure turns into a nightmare! Your loved one is taken away. What will you do? A desperate young stallion that seeks out an ancient evil to take revenge on the humans that butchered his mother and father. ("You can't trust them! They would have found a way to foil your plan! Trust me, humans are nothing but trouble and they all deserve to die!") An evil beast that uses treachery, deception, brute force and even magic to achieve his thousand year old dream of becoming human. ("You remember the freedom, the clarity of thought, the power of those sweet thumbs!" ... "I can give that back to you." ... "I can make you human again.") A love strewn young stallion that will do anything to save his...
	Joe Sorren: In Celebration of Balance & Opposable Thumbs by Joe Sorren (Author) In Celebration of Balance & Opposable Thumbs is an inspirational collection of paintings by Joe Sorren. A full color, archival edition, over 160 pages celebrates the past 10 years of Joe's love for paintings. All books individually shrink wrapped, and cartoned and feature embossed type on cloth cover with full color inset on front cover.
	Opposable Thumbs by Suzanne Hudson (Author) Fiction. In this premier collection of stories, OPPOSABLE THUMBS, Suzanne Hudson reignites literary interest in her work that has laid dormant for years since she turned her back to the literary world after winning the Hackney Literary Awards competition as well as being published in Penthouse magazine and New Writers magazine. In this collection of shorts, "integrations, incest, white trash, and God...it's all here, in a bitter-sweet meringue. Suzanne Hudson's hilarious and moving stories tackle some of the South's major themes without flinching"-Tom Franklin. "Hudson writes like a fallen angel. Her characters may have one foot in heaven, and the other in hell, but she touches them with an ironic humor and a fiery grace"--William Gay.
	Monkey Island, Or, the Advantage of Opposable Thumbs (Adventures of Charlie) by Steve Shreve (Author) In search of treasure on Monkey Island, Charlie helps the monkeys to defeat the terrifying ghost who's threatening to give them wet willies! But is the ghost what he seems, and will Charlie get the treasure? Follow Charlie on five wacky and wonderful adventures where he comes face to face with a host of bad guys in this new, hilarious, illustrated series.
	Opposable Thumbs Volume 1 (v. 1) by Dean Haspiel (Author), Josh Neufeld (Author) Opposable Thumbs is Dean Haspiel's stories of a born & bred New Yorker and the trials and tribulations of living in the big bad city which serves as the backdrop for the informed, existential expression in his sociological comics. In Opposable Thumbs, Haspiel unfolds existential, uproarious, compassionate stories full of personal wisdom. Even the bleakest and grubbiest settings are lovingly, lusciously rendered by Haspiel's sharp brush in one of the most recognizable styles in alternative comics, and "quiet" domestic scenes veritably simmer with graphic impact. Thoroughly conquering the territory Dean began to explore in the critically acclaimed two-man anthology Keyhole (with Josh Neufeld), Opposable Thumbs looks like the new front-runner in autobiographical storytelling. With a...
	Opposable Mind: Winning Through Integrative Thinking by Roger L. Martin (Author) If you want to be as successful as Jack Welch, Larry Bossidy, or Michael Dell, read their autobiographical advice books, right? Wrong, says Roger Martin in "The Opposable Mind". Though following 'best practice' can help in some ways, it also poses a danger: by emulating what a great leader did in a particular situation, you'll likely be terribly disappointed with your own results. Why? Your situation is different. Instead of focusing on what exceptional leaders do, we need to understand and emulate how they think. Successful businesspeople engage in what Martin calls integrative thinking creatively resolving the tension in opposing models by forming entirely new and superior ones. Drawing on stories of leaders as diverse as AG Lafley of Procter & Gamble, Meg Whitman of eBay, Victoria Hale...
	The Panda's Thumb: More Reflections in Natural History by Stephen Jay Gould (Author) "Gould is a natural writer; he has something to say and the inclination and skill with which to say it."—P. B. Medawar, New York Review of BooksWith sales of well over one million copies in North America alone, the commercial success of Gould's books now matches their critical acclaim. Reissued in a larger format, with a handsome new cover, The Panda's Thumb will introduce a new generation of readers to this unique writer, who has taken the art of the scientific essay to new heights.
	Opposable Thumb by Joe Elliot (Author) Poetry. This is Joe Elliot's second collection of pitch-perfect poems. "OPPOSABLE THUMB is essential reading. In these poems, Joe Elliot brings a whopping arsenal of technique to the table to create a sumptuous feast of meaning without equal signs or slashes...Here, song is thought. It all rings true. Essential the way mindfulness is essential. Enjoy the view" -Mitch Highfill. "How has the world limped along for so long without Joe Elliot's new book? If you want to relearn language, please read these poems, which release the kinetic potential of the page like toasters dropped into bathtubs" -Marcella Durand. "Opposable Thumb is a welcome reminder that, in the social world, we are living with the animals. Joe's poems form a kind of sectarian hymnal, a nondenominational performance score...
	Joe Sorren Volumes 1 & 2 (Volume 1, In Celebration of Balance and Opposable Thumbs & Volume 2, When She Was Camera, set of 2 volumes) b 2 Vol. set in black cloth slipcase. Joe Sorren (born 1970, Chicago) is an American conceptualist lowbrow artist. Sorren grew up in Arizona and began painting in 1991. Two years later he earned a BFA from Northern Arizona University. His artwork has appeared in various publications, including The New Yorker, Time and Rolling Stone. Warner Bros. and Atlantic Records have also used his art; he created the cover for the Tweaker album The Attraction to All Things Uncertain and "2 a.m. Wakeup Call."[1] His first solo exhibit was in 1995, in 2010 he is preparing for his first museum retrospective in November. He is known for inspiring a modern genre of artists. A mural of his adorns an outdoor wall at Heritage Square in Flagstaff, Arizona. The 40 feet (12 m) by 30 feet (9 m) painting took 9...
	Opposable Thumbs #1 by Dean and Harvey Pekar Haspiel (Author)