Anthropology.net

Many have written how the term ‘junk DNA’ is an imperfect one, and how junk DNA may have a tangential role in evolutionary changes. A new study published in Science visits this topic, specifically focusing on repetitive non-coding sequences in and around promoter regions of the human genome. The authors of this study have published their findings under the title, “Unstable Tandem Repeats in Promoters Confer Transcriptional Evolvability.”

DNA Packaging

The findings concluded that the repeats affect the activity of neighboring genes by way of how tightly the downstream DNA is wrapped around a complex of proteins collectively called a nucleosomes. A nucleosome is one of the half dozen packaging features of the eukaryote genome which allows a genome that is 3 billion base pairs long or 6 feet in length to be squeezed into a tiny little nucleus. About 167 basepairs wrap around one nucelosome. DNA that is more wrapped around a nucleosome is harder to be activated, and thus otherwise non-coding/junk tandem repeats of sequences determine how tightly the local DNA is wrapped around these protein complexes.

The extra cool finding about this paper is that the tandem repeats are very unstable, as you possibly could tell from the title. The authors found out that the number of repeats changes a lot during DNA replication, as if the DNA pol III exonucleases don’t bother proof-reading these areas! These changes affect the local DNA packaging, which in turn alters gene activity. In this way, unstable junk DNA is one of the faster acting mechanisms in altering gene activity with each cellular division.

As an extra step, the researchers conducted a experiment investigating the impact of these tandem repeats on yeast cells. They found out that when a repeat is present near a gene, it is possible to select yeast mutants that show vastly increased activity of this gene. But, when the repeat sequences were removed, this fast evolution was impossible.

So what does this all mean for human evolution? Well, unstable pieces tandem repeats of ‘junk’ non-coding DNA are one of the many ways of regulating gene expression and honing on when a gene’s activity can enable organisms like humans to quickly adapt to changes in their environments.

Vinces, M., Legendre, M., Caldara, M., Hagihara, M., & Verstrepen, K. (2009). Unstable Tandem Repeats in Promoters Confer Transcriptional Evolvability Science, 324 (5931), 1213-1216 DOI: 10.1126/science.1170097

FOXP2 is one of my favorite genes. I studied it extensively while getting my Master’s degree and wrote about it several times on Anthropology.net. For those that do not know much about it, I’ll quickly introduce it. FOXP2 is a transcription factor gene, which means it controls the expression and regulation of many other genes. It is significant in that it is implicated in human language.

I caught news of a new study on FOXP2 today while reading Nicholas Wade’s article in the New York Times about a hot-off-the-press Max Planck study published in Cell on FOXP2. The study comes from Svante Pääbo‘s lab, who created a strain of transgenic mice with the human FOXP2 variant and noted that these mutant mice made whistles that had a slightly lower pitch than ones with the wild-type FOXP2 gene.

The study has been published as an open access paper under the title, “A Humanized Version of Foxp2 Affects Cortico-Basal Ganglia Circuits in Mice.” There are more findings tucked inside the paper that indicate the impact of the human FOXP2. Aside from the changes in dopamine levels, the most interesting one is the increased axonal and dendritic length of medium spiny neurons in the basal ganglia by 80% when compared to FOXP2^wt. These neurons coordinate the movement and timing of multiple organ systems. Check out the differences for yourself:

Foxp2(hum) Increases the Length of Dendritic Trees

The authors hypothesize on the meaning behind this change in these neurons,

“Currently, one can only speculate about the role these effects may have played during human evolution. However, since patients that carry one nonfunctional FOXP2 allele show impairments in the timing and sequencing of orofacial movements (Alcock etal., 2000,Watkins etal., 2002a), one possibility is that the amino acid substitutions in FOXP2 contributed to an increased fine-tuning of motor control necessary for articulation, i.e., the unique human capacity to learn and coordinate the muscle movements in lungs, larynx, tongue and lips that are necessary for speech (Lieberman, 2006). We are confident that concerted studies of mice, humans and other primates will eventually clarify if this is the case.”

What’s also curious is that the mutant FOXP2 mice don’t seem to have any other effects on other organs, despite the fact that FOXP2 is pretty much ubiquitously expressed all over. It seems like the only manifestations of a human variant showed up in the neuron length and dopamine levels of the brain and ultimately vocalization behaviors. This is an excellent paper which investigates the functional differences of FOXP2, and I recommend you downloading a copy and reading it for yourself.

I’ve successfully completed my first term of medical school, and realized I have a lot of free time so I’ve decided to pick up blogging during my short summer break in order to prevent brain rot. Today, I noticed an interesting anthropology-medicine news bit pass by my RSS reader and wanted to share it with y’all. The paper behind the news announces the finding of the oldest evidence of leprosy in India, specifically the Balathal site nearby Udaipur in the state of Rajasthan, India. It has been published in the open access journal, PLoS ONE, under this title, “Ancient Skeletal Evidence for Leprosy in India (2000 B.C.).”

The significance of this finding is that it pushes the existence of leprosy back by 2,000 years, from biblical times, with physical evidence.

Balathal, Indus/Harappan Site in Rajasthan, India

The skeleton of this middle aged (37 or so years old) adult male was buried about 4,000 years ago during a time which Balathal was a large agrarian settlement at the margins of the Indus (or Harappan) Civilization. He displays:

• Erosive lesions at the supraorbital region and glabella
• Remodeling of the margin of the nasal aperture, including the anterior nasal spine,
• Bilateral necrosis of the infraorbital region of the maxilla
• Resorption of the alveolar region of the maxilla with associated antemortem tooth loss
• Pitting near the midline and in the alveolar region of the palatine process
• Root exposure, alveolar resorption, antemortem tooth loss to the mandible and a small apical abscess at the left lower third premolar
• Ventral wedging, osteophytosis, and ankylosis to the cervical vertebrae
• Periostosis to the left tibia

These are all characteristics of leprosy, treponemal infection, leishmaniasis, sinus and oral infections, tuberculosis, osteomyelitis and non-specific infection in the post-crania. But differential diagnosis ruled out all of the other pathologies other than leprosy.

The individual was excavated between 1994–1997. Lots of hallmarks in human existence occurred during this time period, some being inventions in system of writing, standardized weights and measures, monumental architecture, and trade networks that stretched to Mesopotamia and beyond. While the pathophysiology of leprosy is up in the air, it is not surprising that communicable diseases, even not very contagious ones like leprosy, also blossomed during the rapid sedentarisation of human populations.

The cranium of individual 1997-1

Leprosy is a granulomatous (nodule) disease of the peripheral nerves and upper respiratory tract mucosa, caused by immune system unsuccessfully trying to sequester the infectious bacterium Mycobacterium leprae and Mycobacterium lepromatosis. Unlike popular belief, body parts falling off is not the primary symptom of leprosy, but rather skin lesions are the main external manifestation of the disease. The damage to the nerves affects blood flow and ultimately causes necrosis of tissue, which happens in during the advanced lepromatous stages.

Anterior view of the mandible from individual 1997-1

What is curious is that descriptions of leprosy have been noted in Ebers papyrus, an Egyptian medical document and the Atharva Veda, a Sanskrit holy text, which both refer to the disease as early as 1,550 B.C., a few hundred years after this individual died. I wonder if this guy was one of the first Lepers then? Gwen Robbins, first author of the publication, expressed interest in recovering DNA from the Mycobacterium leprae and comparing it to strains common in Africa, Asia and Europe today in order to shed additional light on the origin and transmission routes of this disease, in fact she hypothesized that the disease migrated to the subcontinent from Africa, at a time when substantial interaction among populations throughout Asia, the Middle East, and Africa.

Elements demonstrating pathological conditions in the postcranial skeleton of individual 1997-1.

Robbins, G., Tripathy, V., Misra, V., Mohanty, R., Shinde, V., Gray, K., & Schug, M. (2009). Ancient Skeletal Evidence for Leprosy in India (2000 B.C.) PLoS ONE, 4 (5) DOI: 10.1371/journal.pone.0005669

The face of the first European, reconstructed by forensic artist Richard Neave.

Using the incomplete skull and jaw bone in a cave in the southwest of the Carpathian Mountains in Romania, scientists had revealed for the first time the face of the first European.

Scientists doesn’t know if this modern human is a male or a female but using radiocarbon analysis they found that this individual lived around 34,000 to 36,000 years ago. Around this time, Europe is home to both Neanderthals and modern humans. Modern humans first arrive to Europe from Africa.

The skull of this individual is human-like, though there are also some archaic traits such as large molars. Some scientists speculated that this skull belongs to a Neanderthal and modern human hybrid though it was disproved by many experts.

Richard Neave, a forensic artist used clay to reconstruct this individual for a BBC program about the origins of the human race and evolution.

Originally posted on Prancing Papio.

A new genetic survey by Dr. Sarah A. Tishkoff of the University of Pennsylvania and her team has found that modern humans originated in an area between Namibia and Angola, on the coast of southwest Africa. Read the New York Times Article: Eden? Maybe. But Where’s the Apple Tree?

However, this harsh and inhospitable area is nothing Eden-like, they said. The origin of a species, like modern humans, is generally pinpointed to a place where its individuals show the highest genetic diversity. After comparing genetic data from populations around the world, the researchers pinpointed the population with the highest genetic diversity – somewhere on the coast of southwest Africa near the Kalahari Desert. The Bushmen or San people currently call this area their home.

The researchers have also calculated the exit point of modern humans that left Africa about 50,000 years ago. The exit point lies in an area of the African coast of the Red Sea. If the “Out Of Africa” theory holds true, this tribal group of about 150 people that left Africa at that exit point displaced other archaic Homo sapiens populations from different continents, giving rise to the current modern human populations.

Originally posted on The Prancing Papio.