Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Myosin mutant points to human origins

25.03.2004


First protein difference between humans and primates that correlates to anatomical changes in early hominid fossil record



In an effort to find the remaining genes that govern myosin--the major contractile protein that makes up muscle tissue--researchers at the University of Pennsylvania School of Medicine have made a discovery that may be central to answering key questions about human evolution.

Published in the March 25 issue of Nature, Penn researchers have found one small mutation that undermines an entire myosin gene. Their estimated dating for the appearance of this mutation places it at about 2.5 million years ago, just prior to a period of major evolutionary changes in the hominid fossil record. These include the beginning of larger brain size, so important in making us human. While the characterization of this mutation may better help understand such genetic diseases as muscular dystrophy, this finding has potentially wider implications for re-interpreting long-held notions about the appearance and early evolution of the genus Homo.


Anthropologists have long debated how humans evolved from ancestors with larger jaw muscles and smaller brains. This newly discovered mutation seems responsible for the development of smaller jaw muscles in humans as compared to non-human primates. These converging lines of evidence suggest the question: Did this genetic mutation lift an evolutionary constraint on brain growth in early humans?

In a classic case of scientific sleuthing, Hansell Stedman, M.D., Associate Professor of Surgery, Nancy Minugh-Purvis, Ph.D., Director of Advanced Gross Anatomy, Department of Cell and Developmental Biology, and colleagues took their discovery of a mutation that prevents the expression of a variety of myosin -- designated MYH16 on chromosome 7 -- to its ultimate context: what makes humans different from other primates.

"Around the lab, we jokingly call this the ’room for thought’ mutation, since we had to involve scientists from several disciplines to make sense of the possible domino effects," says Stedman. "In other words, we had to do a lot of experiments to connect the dots from DNA to RNA to protein to muscle fiber to whole muscle to boney attachment sites. Then in looking at the modern and fossil skulls it dawned on us that we just might have to look ’outside of the box’ to appreciate the real significance of the initial findings."

The study began with the discovery of an unexpected similarity between an "anonymous" piece of the human genome sequence and some previously studied genes known to power muscle contraction. The surprise came when a small, inactivating deletion was found in this sequence, perhaps explaining why the computer programs had previously passed by the area without recognizing it as a gene.

To determine whether the mutation was a rare form of an active gene and not a mistake introduced by the technical nature of the investigation, the team tested DNA samples from geographically disparate human populations. They found the gene-inactivating mutation in all modern humans sampled--natives of Africa, South America, Western Europe, Iceland, Japan, and Russia. However, the mutation was not present in the DNA of seven species of non-human primates, including chimpanzees.

Additional studies showed that versions of this gene in non-human primates bear the imprint of a critically important function for the animal, which implies that the mutation afflicts all humans, in one sense of the word, with the same inherited muscle "disease." The intriguing questions became, what is the "disease" and why is it so common?

To find out in which tissue the MYH16 gene is normally activated, the investigators examined a wide range of muscle types in the readily available macaque monkey and humans. In macaques, they found the MYH16 protein was only made in a group of related muscles in the head, those involved principally with chewing and biting. In humans, they found that messenger RNA, which translates the genetic code into workaday proteins, was still active in these muscles, but no protein was being made by virtue of the mutation.

But how does this relate to the anatomical differences seen in modern humans versus non-human primates? First, the jaw muscles and their bony attachments in apes and monkeys are much larger and more powerful than in humans. At the tissue level, the researchers found that macaque chewing and biting muscles are nearly ten times as large as in humans, which correlates with the fact that MYH16 protein is made in macaques and not in humans. So maybe the "disease" is a weaker bite, raising a question as to why this mutated version of the gene could have become so widespread among modern humans.

By comparing a portion of the MYH16 gene sequence in humans to that in five other animals--quantifying the so-called molecular clock--the researchers calculated that the inactivating mutation appeared in a hominid ancestor about 2.4 million years ago, after the lineages leading to humans and chimpanzees diverged. Shortly thereafter, roughly 2.0 million years ago, the less muscled, larger brained skulls of the earliest known members of the genus Homo start to appear in the fossil record.

From this the investigators postulated that the first early hominids born with two copies of the mutated MYH16 gene would show many effects from this single mutation--most notably a reduction in size and contractile force of the jaw-closing muscles, some of which exert tremendous stress across and/or cause deposition of additional bone atop growth zones of the braincase. "The coincidence in time of the gene-inactivating mutation and the advent of a larger braincase in some early Homo populations may mean that the decrease in jaw-muscle size and force eliminated stress on the skull, which ’released’ an evolutionary constraint on brain growth," says Minugh-Purvis. Indeed, aspects of the evolutionary trend of shrinking jaws and teeth, resulting in the lighter, more delicate structure found in humans today, roughly coincided with the increase in brain size characterizing the evolution of Homo over the past two million years.

Dr. Stedman is also a member of the Pennsylvania Muscle Institute at Penn. Dr. Minugh-Purvis is also adjunct assistant professor in Cell Biology and Anatomy at the University of Pennsylvania School of Dental Medicine; growth specialist in the Facial Reconstruction Center, Division of Plastic Surgery, Children’s Hospital of Philadelphia; and a research associate at Penn’s University Museum of Archaeology and Anthropology. Other Penn researchers collaborating on this work are Benjamin W. Kozyak, Anthony Nelson, Danielle M. Thesier, Leonard T. Su, David W. Low, Charles R. Bridges, Joseph B. Shrager, and Marilyn A. Mitchell.



The research was supported in part by grants from the National Institutes of Health, Muscular Dystrophy Association, Association Française contre les Myopathies, Veterans Administration, and Genzyme Corporation. The authors have no competing financial interest in this work.

PENN Medicine is a $2.2 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation’s first integrated academic health system).

Penn’s School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

Penn Health System consists of four hospitals (including its flagship Hospital of the University of Pennsylvania, consistently rated one of the nation’s "Honor Roll" hospitals by U.S. News & World Report), a faculty practice plan, a primary-care provider network, three multispecialty satellite facilities, and home health care and hospice.

Karen Kreeger | EurekAlert!
Further information:
http://www.med.upenn.edu/

More articles from Life Sciences:

nachricht Glycosylation: Mapping Uncharted Territory
21.09.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Glycosylation: Mapping Uncharted Territory

21.09.2017 | Life Sciences

Highly precise wiring in the Cerebral Cortex

21.09.2017 | Health and Medicine

Did marine sponges trigger the ‘Cambrian explosion’ through ‘ecosystem engineering’?

21.09.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>