Thursday, December 15, 2011

Endangered orangutans offer a new evolutionary model for early humans

Starving orangutans in Borneo are yielding new ideas about human evolution. The way in which the orangutans cope with food-limited environments may give information about what early human ancestors were facing.
The study is being led by Nathaniel Dominy, an associate professor of anthropology at Dartmouth College. The apes that gave rise to the earliest human ancestors had teeth that are much like orangutan teeth, particularly those living in Borneo. Dominy suggests that the orangutans' diet may have exerted a selective pressure on their molar teeth. If we understand the physical properties of their food, then we may have some idea of why humans evolved the teeth that we have.
The five-year study described in the Biology Letters paper documents the adaptive metabolism of these apes in the protein-deficient times that characterize the environment for the majority of a four- to five-year cycle. Their urine was collected and analyzed for dietary markers, such as ketones, which increase when the body breaks down fat for energy. When fruit abundance was lowest, the ketones surged, demonstrating that the animals were burning their fat reserves—using more energy than they were taking in. When the fat is depleted, however, muscle tissue is cannibalized.
Professor Dominy considers the lean years for orangutans on Borneo to be a selective pressure that led to evolutionary adaptations since the population became isolated 400,000 years ago, and the larger molars and more robust jaws developed in response to the hard, tough foods they consumed during the periods between fruit availability. Recent studies of wear patterns on the huge molars of early hominids suggest that they only ate a more physically challenging diet some of the time; they may be displaying an adaptation that helped them to get through evolutionary pinch points, similar to what the Borneo orangutans encounter.

Scientists Discover Second-Oldest Gene Mutation

A new study, led by researchers with the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, has identified a gene mutation that they estimate dates back to 11,600 B.C., making it the second oldest human disease mutation yet discovered. They estimate that the mutation arose in the Middle East some 13,600 years ago, and is described in people of Arabic, Turkish and Jewish ancestry. It causes a rare, inherited vitamin B12 deficiency called Imerslund-Gräsbeck Syndrome (IGS).

It originated in a single, prehistoric individual and was passed down to that individual’s descendants. This is unusual because such “founder mutations” usually are restricted to specific ethnic groups or relatively isolated populations.

Because the mutation was found in such diverse populations, the researchers were unsure whether it was a true founder mutation that first arose in one individual and was passed down, or whether it was simply a mutation that recurred frequently over time in different populations. Analysis of the gene sequences on either side of the mutation (the haplotype in both the Muslim and Jewish families), pointed to a single mutational event rather than repeated events.

Principal investigator Stephan M. Tanner says, “Our findings permit reliable genetic diagnostics in suspected cases of IGS in that this mutation should be considered first when genetically screening patients from these populations.” This mutation accounts for more than half of the cases in the aforementioned populations and for about 15 percent of cases worldwide.

ADHD - Four Genes Linked To The Disorder

Four gene variants, all members of the glutamate receptor gene family, appear to be involved in vital brain signaling pathways in a group of children with attention deficit hyperactivity disorder (ADHD). The genes involved affect neurotransmitter systems in the brain that have been implicated in ADHD, and now there is a genetic explanation for this link that applies to this subset of children.

ADHD is fairly common and tends to run in families. Though it is considered by many to be the most commonly over-diagnosed disorder, it is thought to affect about 7% of kids of school age and a smaller percentage of adults.

Researchers from the Center for Applied Genomics at The Children's Hospital of Philadelphia conducted whole-genome analyses of 1,000 kids with ADHD compared with 4,100 others of the same age who did not have ADHD. They looked for duplications or deletions of DNA sequences (copy number variations, or CNVs), and then compared the preliminary findings with various cohorts, made up of 2,500 kids with and 9,200 without ADHD. They identified They identified four genes with a considerably greater number of CNVs in the ADHD children. They were all glutamate receptor (GMR) genes. The one with the strongest result was gene GMR5. Members of the GMR gene gamily, aong with genes they interact with, affect nerve transmission, the formation of neurons, and interconnections in the brain. Glutamate is an amino acid and neurotransmitter. The fact that children with ADHD are more likely to have alterations in these genes reinforces previous evidence that the GRM pathway is important in ADHD.

Co-first author Josephine Elia, M.D., says, "This research will allow new therapies to be developed that are tailored to treating underlying causes of ADHD. This is another step toward individualizing treatment to a child's genetic profile."

Wednesday, December 14, 2011

A Mutation in the Thyroid Hormone Receptor Alpha Gene

Today in the New England Journal of Medicine online, a study was published which describes the finding of a genetic cause of hypothyroidism.  The effects of thyroid hormones manifest through their two different types of receptors: alpha and beta.  This article considers a case study of a young girl whose hypothyroidism is caused by a nonsense mutation in genes encoding her alpha receptors rather than by abnormal levels of hormone production.  The study used whole-exome sequencing to find this heterozygous genotype coding for a protein which inhibits the receptor. The article includes images and graphs showing the phenotypic traits and abnormalities manifested in this case by a mutation in receptor rather than hormone production.

Tuesday, December 13, 2011

World's First Super Predator had Remarkable Vision

New fossil discoveries from Kangaroo Island, Australia reveal a fascinating truth: the world's first super predator, the metre-long Anomalocaris had excellent eye-sight. The eyes of this 500 million-year-old marine creature were discovered, exceptionally preserved, and have been able to tell scientists that this apex predator had highly acute vision, on par with that of living insects and crustaceans.
Even without its eyes, the Anomalocaris was a fearsome predator. At the top of its food chain, a large body, giant grasping claws at the front of its head and sharp teeth made it quite a force to behold. More fossils of its excrement, full of trilobites, bolster the fact that this thing was a killing machine. With this new discovery, another piece of the puzzle is placed.
The stalked eyes, multi-faceted as in flies or crabs, are incredibly large. Up to 3 cm in length and containing over 16,000 lenses, they are numbered among the largest to have ever existed. These eyes confirm the close relation this creature had to arthropods, and that this visual organ made an early appearance in evolutionary history. In fact, it even appeared before the exoskeleton or locomotive legs.


A Small Step for Lungfish, a Big Step for the Evolution of Walking

Well, it looks as if it is once again time to completely rewrite how we think about the early evolution of land-dwelling creatures. That is because new information has come out on the walking abilities of the African lungfish, one of the more unlikely candidates for locomotion. Still, scientists at the University of Chicago have deduced the incredible ability of the lungfish to walk due to its very thin pelvic limbs. While this ability was previously thought to have originated with tetrapods, it now appears as if it may have been the earlier ancestors of this lungfish.
In fact, scientists are even now reexamining fossil tracks previously concluded to be left by tetrapods. Melinda Hale, an associate professor, now states that, "Aquatic animals with fundamentally different morphologies and that aren't tetrapods could potentially make very similar track patterns." But, why was this not discovered sooner? That lies in the structure of the lungfish's strangely thin limbs. When Heather King, the lead author the study, decided to monitor the movements of the lab's lungfish, she discovered that the lungfish could lift and propel itself on these tiny limbs.
It is indeed lucky to have a live specimen of such incredible genetic history to be able to work with hands-on in the lab. In fact, this was probably the only way scientists would have made this discovery. As King conceded, "If you were just to look at the bones, like you would with a fossil, you might not even know these motions could occur." The fact that it has this locomotive ability may be due to the change in gravity underwater. By filling up its front with air, the lungfish could become just buoyant enough to be able to bound and run as we now know it is able to do.


New View of How Humans Moved Away from Apes

Anthropologists have recently revised their view of how early human societies were structured. This shift ultimately brings new insights into the evolution of humans from apes. This new belief is concerned with how early human groups would have been more cooperative and willing to learn from one another than the chimpanzees from which our ancestors split.

Anthropologists have assumed until now that hunter-gatherer bands consist of people fairly closely related to one another, much as chimpanzee groups do, and that kinship is a main motive for cooperation within the group. Natural selection, which usually promotes only selfish behavior, can reward this kind of cooperative behavior, called kin selection, because relatives contain many of the same genes.

A team of anthropologists led by Kim R. Hill of Arizona State University and Robert S. Walker analyzed data from 32 living hunter-gatherer peoples and found that the members of a band are not highly related. Fewer than 10 percent of people in a typical band are close relatives, meaning parents, children or siblings, they report in Friday’s issue of Science.

The finding corresponds to an influential new view of early human origins proposed by Bernard Chapais, a primatologist at the University of Montreal. Dr. Chapais showed how a simple development, the emergence of a pair bond between male and female, would have allowed people to recognize their relatives, something chimps can do only to a limited extent. When family members dispersed to other bands, they would be recognized and neighboring bands would cooperate instead of fighting to the death as chimp groups do.

By: Alwin Firmansyah

Paleoanthropologists have recently discovered an apelike creature with human features, whose fossil bones were discovered in a South African cave. Les Berger of the University of Witwatersrand in Johannesburg, the founder of the fossils, believes that the new species is the most plausible known ancestor of archaic and modern humans. He also believes that if accepted, this finding would radically redraw the present version of the human family tree, placing the new fossils in the center. The new species, in his view, should dislodge Homo habilis, the famous tool-making fossil found by Louis and Mary Leakey, as the most likely bridge between the australopithecenes and the human lineage. In this particular case, there are many uncertainties regarding the fossil record from that time, including when the human lineage first emerged and how Homo habilis fits in the picture. The principal significance of the new fossils is not that Australopithecus sediba is necessarily the direct ancestor of the human genus, other scientists said, but rather that the fossils emphasize the richness of evolutionary experimentation within the australopithecine group.

A Whole New Meaning for Thinking on Your Feet

In a recent study by Smithsonian researchers, it was discovered that, for many tiny spiders, their brains are literally too big to fit inside their heads. In fact, they're even too big to fit inside their bodies. In an ongoing study on miniaturization and its effects, researchers examined nine species of spiders of varying size and determined that, while spiders get smaller their brains stay about the same size, and wind up overflowing into their body cavities.
William Wcislo, one of the staff scientists for the research, explained that even the tinnier spiders must maintain the amount of brain space needed todo complex behavior like weaving webs. Therefore, "the central nervous systems of the smallest spiders fill up almost 80 percent of their total body cavity, including about 25 percent of their legs." The smaller the spider, the more troublesome this can be for the animal. Tiny spiderlings often will have deformities and bulges in their bodies due to the excess amount of brain.
There is a biological basis for why this excess of brain must be the case. The diameter of nerve fibers cannot be smaller without becoming too thin, disrupting the flow of ions that carry the nerve signals. If the nervous system cannot be made smaller, the only alternative is to accommodate it with more room. By Haller's rule, a general rule for all animals, "as body size goes down, the proportion of the body taken up by the brain increases." We see this in all animals, even humans.
Seemingly, these large brains are not cumbersome. Much of what small spiders eat can easily be converted into energy to fee the brain. Larger spiders, such as the Nephila clavipes, weighing 400,000 times more than the smallest spiders in the study, clearly needs more food and energy to support its substantial body mass.


New Discovery in Europe

A group of paleontologists have just discovered what is believed to be the oldest known skeletal remains of anatomically modern humans in all of Europe. The scientists who made the discovery and others who study human origins say they expect the findings to reignite debate over the relative capabilities of the immigrant modern humans and the indigenous Neanderthals. Although the actual skeletal remains were found over four decades ago, scientists have recently re-examined the fossils and concluded that they had been previously underestimated possibly contributing to incorrect evaluations on the other parts of the remains. The earliest reliably dated European modern human specimen came from the Pestera cu Oase site in Romania.

In tests conducted at the Oxford Radiocarbon Accelerator Unit in England, the baby teeth from Italy were dated at 43,000 to 45,000 years old. And in the absence of early fossils, archaeologists had not been sure who made some of the stone tools they were uncovering, the arriving humans or the Neanderthals. It had been generally assumed that modern humans probably entered Europe at least as early as 45,000 years ago, based on changing patterns of artifacts that soon followed. Anyhow, this new discovery will help researchers evaluate some of the evolutionary events in which society has been interested in for decades.

By Alwin Firmansyah

Monday, December 12, 2011

Genomics of Cardiovascular Disease

In this article published December 1, 2011, Doctors Christopher O'Donnell and Elizabeth Nabel review genetic and genomic studies of the past decade which have contributed to our understanding of cardiovascular mechanisms.  As the leading cause of death in the United States, cardiovascular disease has been greatly studied, is increasingly understood, and has become much easier to treat.  The article addresses alleles at loci associated with heart failure and arrhythmias and considers targeted and genome wide DNA sequencing as applied to cardiovascular medicine.  The article thereby delivers a comprehensive overview of recent research in this area through both bottom-up and top-down approaches.  Attached also is an interactive timeline, making the material especially accessible.

Pictured: "Genomic Locations of Genetic Variants Associated with the Risk of Myocardial Infarction and Heart Failure"

You Don’t Have to Hit the Gym to Bulk Up - Juliana Canfield (Dec. 2, 2011)

An international team of scientists has created super-strong, high endurance mice and worms by suppressing a natural muscle growth inhibitor, suggesting treatments for age-related or genetics-related muscle degeneration are within reach.

The collaboration took place among the Salk Institute of Biological Studies and two Swiss institutes, the Ecole Polytechnique Federale de Lausanne, and the University of Lausanne.

The study suggests that here is a tiny inhibitor that could be responsible for determining the strength of our muscles. This conclusion and procedure makes the work being done somewhat unique, because most studies in this area focus on promoting genetic accelerators instead of focusing on inhibiting genetic inhibitors. NCoR1, a gene regulator usually inhibits muscle growth. So when NCoR1 is suppressed, the body is able to send more energy to muscle cells and enhance cellular activity in the muscles. The scientists genetically removed the NCoR1 from fat and muscle cells in mice and in certain types of worms. In the absence of NCoR1, muscle tissue developed much more effectively, and were ultimately more massive and had more cellular mitochondria than the muscles of the mice where NCoR1 was still at work. The mice’s endurance and cold tolerance also dramatically improved.

This discovery enables scientists to give the benefits of exercise to sedentary mice by manipulating NCoR1. Currently, just manipulation is purely genetic, but this work could lead to developing drugs molecules or therapeutic solutions for humans who are unable to exercise due to health complications like obesity, diabetes, frailty (due to old age) or immobility (due to accidents). "This could be used to combat muscle weakness in the elderly, which leads to falls and contributes to hospitalizations," Auwerx, one of the scientists working on the study, says. "In addition, we think that this could be used as a basis for developing a treatment for genetic muscular dystrophy." When human trials begin and drug development begins in earnest, there is no question that the athletic community, as well as the medical one, will be greatly interested by the findings.

Sources: Salk Institute (2011, November 21). Tweaking a gene makes muscles twice as strong: New avenue for treating muscle degeneration in people who can't exercise. ScienceDaily. Retrieved December 1, 2011, from­ /releases/2011/11/111121104509.htm; The Study:

Yale scientists identify gene that causes spread of melanoma

An article in Yale News today describes how Yale Cancer Center researchers have identified a gene linked to the metastasis of melanoma. Scientists have long been in interested in understanding the process behind metastasis, which is responsible for the vast majority of melanoma-related deaths. The gene in question is known as CTNNB1, and it codes for the protein beta-catenin. Mutated beta-catenin has been observed in 5-10% of melanoma cases, but only with this study has an increase of the protein been linked to increased metastasis (and decreased beta-catenin linked to the near elimination of metastasis). Understanding metastasis has obvious implications for medicine, but more research is needed to fully understand the gene's role--the researchers of this study revealed that it is part of a network and very much affected by other mutations.

Mutational Dynamics of Microsatellites

Molecular anthropologists use microsatellites for a number of purposes, yet their mutation dynamics are still not well understood. This article contributes to the understanding of the mutation dynamics of this important class of DNA sequence repeats. In particular, it looks at the mutational mechanics of microsatellites. Before doing so, it provides a thorough definition of these mutations, including their multiple other nomenclatures - SSRs (short sequence repeats) or STRs (short tandem repeats). In class and in the textbook I am sure we have seen microsatellites referred to as STRs, but I'm don't believe we've used the name SSR. This is a helpful abbreviation for anyone trying to remember their particular function - that is, that microsatellites are repeats on the genome sequence. This is a minor point, yet it seems helpful to make a note of it, given that this type of VNTR mutation has a name which directly links it to what it actually affects. However, the mutation mechanics the STRs are the true focus of this study and shows data which precisely measures the (relatively high) mutation rates of microsatellites, along with a host of other features of mutation dynamics.

More from Morris Goodman - "founder of molecular anthropology"

I posted an article earlier which credits Morris Goodman as being the founder of the field of molecular anthropology. This article shows that, while he may have founded the field, he was not always correct in his conclusions. For example, this article sites a study of his which used immunological tests to demonstrate the close relationships between chimpanzees, humans, and gorillas. In this study from the 1960s, he posited that chimps and gorillas should join humans in the class Hominidae, which challenged established taxonomies. As technology improved, Goodman was able to look at protein and DNA sequence data, which provided more accurate information regarding genetic diversity. Still, this article shows that he continued to defy the established order despite the increased availability of more precise data late into his career.

Waiting for Sequences: Morris Goodman, Immunodiffusion
Experiments, and the Origins of Molecular Anthropology

Study Indicates Population Specific Founder Mutation in Jewish Community

This study is certainly relevant to what we've been studying since the midterm. More importantly, it helped develop a new paradigm to assess and treat blindness using molecular methods. What sparked the study that led to the treatment of blindness in a North African Jewish population was the discovery of a shared homozygous region among seven patients, which led researchers to conclude that there was a founder mutation specific to this population and ultimately to the development of medical procedures that would target the genes which were pinpointed as having caused the founder effect - and previously unexplained levels of heritable blindness - among a high number of individuals within population.

Molecular Anthropology Meets Genetic Medicine to Treat Blindness in the North African Jewish Population: Human Gene Therapy Initiated in Israel

An interesting article that contributes to the debate about the "Peopling of the New World"

This study observed the crania of Paleoindians and Archaics from North and South America and compared their observations to a worldwide database. This study also looked at Fst statistics derived from their subjects in order to conclude that the earliest North and South Americans came from an East Asian population. Essentially, it confirmed what scientists already know from looking at fossil records and genomic data - that the "peopling of the new world" involved a migration of a certain sub-population from Eurasia, across some sort of land bridge (now submerged due to the melting of the polar ice caps), to the Americas. 

A Population Genomic Analysis of the Peopling of the New World;2-L/abstract

Morris Goodman, "Founder of Molecular Anthropology" (1925-2010)

This article credits Morris Goodman as being the founding father of the field of molecular anthropology. During his 52 year career, Goodman sought to answer three questions of evolutionary biology using early molecular anthropological methods: 1) What is the placement of humankind in the natural world? 2) What is the genetic basis of humankind? 3) Did humankind's traits evolve recently or are they connected to more ancient roots?

Goodman's work began in the 1960s and continued until his death in 2010. Throughout his extensive career, he published hundreds of articles and received a number of awards - including the Charles Darwin lifetime achievement award - and other honors for his contributions to the field of molecular anthropology.

Morris Goodman (1925–2010): Founder of the Field of Molecular Anthropology

Saturday, December 10, 2011

Human evolution: a place to rest your weary head

Researchers of early human behavior in South Africa have recently found an artifact that dates back 77,000 years and suggests "how Homo sapiens made the transition to modernity": a comfortable mattress.  Caves in South Africa have been a source of information about early human development, and the most recent discovery came from a cave called Sibudu.  There, Lyn Wadley and her coworkers from the University of Witwatersrand found a bedroom whose floor rose over time as different groups occupied the room and abandoned it again, leaving debris behind.

The oldest layer is 77,000 years old and contains a mattress made of layered plants, a few square meters large.  One section of the mattress interesting contained insecticidal plants while other sections were burned, suggesting Sibudu residents also dealt with pest control across the years.  Other artifacts in the bedroom, inhabited by so many different generations, may help scientists learn about human development and their development of the world around them.  The article notes, "The origins of modern, consumer-good-loving humanity might thus be illuminated by this scene of ancient domestic bliss."

Discovering Sepsis On the Spot

When a doctor suspects that a patient is suffering from blood poisoning, they must draw a blood sample and then send it to a central laboratory for testing. Unfortunately this takes up time and this time could cost the patient his or her life. With the recent development of a biochip though, this will not be a problem in the future. The biochip, which makes it possible to analyze blood right there in the hospital and have results within twenty minutes, was developed by scientists at the Fraunhofer Institute for Physical Measurement Techniques IPM in Freiburg.

The biochip requires a "fully automatic deceive to carry out all the examination steps". In the device red blood cells are separated from the blood and the plasma that remains is guided onto the biochip. Our immune systems produce certain proteins when we suffer from sepsis and there are antibodies on the chip that fit these proteins, so that if these proteins are are in fact present in the blood, the antibodies fish them out and bind them to the chip. A solution containing the appropriate antibodies, which have been marked with a fluorescent dye, is then used to rune the chip. If the patient has blood poisoning the chip lights up and if the patient is healthy the chip stays dark. In the future this biochip will be used to test for different proteins at the same time in one cycle.


A Brighter Future for Hospital Room Cleaning Techniques

"More than 100,000 in North America die every year due to hospital acquired infections at a cost of $30 billion. That's 100,000 people every year who are dying from largely preventable infections." Shocking? I know I was extremely shocked to read this. That is why it was slightly relieving to read in this article that recently a Queen's University infectious disease expert, Dr. Dick Zoutman, in collaboration with Dr. Michael Shannon of Medizone International has developed a disinfection system that may hospital rooms all over the world. Not only that, but it may also be used in food preparation areas and processing plats after outbreaks as well as to stop bed bug outbreaks in hotels and apartments.

The system involves pumping Medizone-specific ozone and hydrogen peroxide vapor gas mixture into the targeted room to completely sterilize everything. It is more effective in killing bacteria than wiping down the room and it is also faster than other methods. The technique imitates the antibodies that Mother Nature uses to kill bacteria in humans. As quoted by Dr. Zoutman, "this is the future."


New Method of Designing Antibodies To Combat Disease

Researchers at Rensselaer Polytechnic Institute have developed a new method to design antibodies aimed at combating disease. Designing antibodies is rather difficult because it requires a very specific combination of antibody loops in order to bind to and neutralize each target. Therefore the arrangement and sequence of the antibody loops is extremely important. Scientists have been unable to realize this as a method for designing antibodies to combat specific ailments thus far due to the incredible complexity of the designing process, but just recently the process was used to create antibodies that target the Alzheimer's protein.

The Alzheimer's protein, the specific protein that causes Alzheimer's disease, sticks to other Alzheimer's proteins to create protein particles, which then damage the normal, healthy functions of the brain. The research led by Assistant Professor of Chemical and Biological Engineering Peter Tessier uses the same molecular interactions that cause these harmful proteins to stick together and form the toxic particles that are a "hallmark of the disease". The good thing is that these new Alzheimer's antibodies only latch on to the damaging clumped proteins and not the unassociated harmless monomers or single peptides. Scientists will need to learns more about this method, but for the future, the researchers see this technique being used to target similar types of protein particles in disorders such as Parkinson's disease and mad cow disease.