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The Genome Ball

Feature Story: The Genome Ball

Forget Those X-Shaped Chromosomes

A Genome Looks Like This

Visitors to the Genome exhibition are frequently intrigued by the Genome Ball, a three-dimensional model of the human genome that represents a creative synthesis of scientific knowledge and technical innovation. For students and adults raised on clinically produced karyotypes – those artificially arranged pairs of X-shaped chromosomes photographed during cell division – the Genome Ball will challenge all their previous (mis)conceptions and show the human genome in a new light.

How did we first begin to grasp the structure of the nucleus? It all began in 1682 when Anton van Leeuwenhoek, a fabric merchant in the Dutch city of Delft, examined blood cells of fish. Leeuwenhoek used a microscope with lenses he’d ground himself, and reported his observations in a letter to the Royal Society:

I came to observe the blood of a cod and of a salmon, which I also found to consist of hardly anything but oval figures … it seemed to me that some of them enclosed in a small space a little round body or globule …

If you’ve looked at human blood under a microscope, that description may sound odd:  Mature red blood cells (RBCs) don’t contain nuclei – do they? You’re right! However, the RBCs of fish (and amphibians and reptiles) do indeed have nuclei, and Leeuwenhoek was the first to describe them. Nevertheless, the Royal Society wasn’t blown away by his letter (after all, how much could a business man with “little fortune and no formal education” know about science?). The “little round body or globule” remained nameless for the next 150 years.

Then, in 1831, the Scottish botanist Robert Brown was studying plant fertilization when he noticed that pollen moved in and out of “ovals” in the plant cells. He called each oval a “nucleus,” a Latin word meaning “nut” or “kernel” – a bit like a black walnut surrounded by its thick green hull. Not only did Brown’s name stick, but his 1833 paper even suggested that the nucleus was probably involved in fertilization and the development of embryos.

The next step in our nuclear narrative was taken by Friedrich Miescher, a Swiss physician who extracted and isolated a previously unknown substance from pus-soaked bandages at the hospital where he worked. White blood cells, a major constituent of pus, have very large nuclei, and Miescher correctly concluded that the substance came from those nuclei. He called it “nuclein.” Today we call it DNA.

How many chromosomes in a human cell?

Although the fine points of cell division were still unexplained, scientists in the early 1900s were eager to learn the number of chromosomes in human cells. However, counting the number of human chromosomes during cell division turned out to be quite a challenge. Even when chromosomes were lined up on the “midline” of a cell, scientists’ counts ranged from 16 to 36.

Evidently, Hans von Winiwarter got tired of these wide-ranging approximations. Using the best microscopes available to him in 1912, he produced early karyotypes by capturing and fixing human cells at the moment of cell division. Despite his best efforts, Winiwarter’s counts ranged from 46 to 49; and while noting correctly that women have two X chromosomes, he mistakenly concluded that males had only one X and no Y.  For the next 40+ years, students were generally taught that human cells contained 48 chromosomes.

Finally, in 1956, the correct value of “46” was confirmed – 22 pairs of autosomes and 1 pair of sex chromosomes in human cells other than eggs or sperm. It’s surprising to learn that Watson & Crick had published their model of DNA’s structure, opening the world of modern genetics, several years before the number of human chromosomes was firmly established!

Good things come in small packages

By the end of the 20th century, knowledge of DNA structure and the mechanisms of cell division had advanced dramatically. Yet, based on their school textbooks, most people still tended to picture chromosomes as the condensed “X-shaped” bodies seen in karyotypes. DNA was known to uncoil between cell divisions, but it was hard to imagine how such long straggling threads (more than 2 meters, or 6 feet, per cell) could pack into a nucleus only 6/1,000,000 of a meter in diameter (smaller than the diameter of a human hair).

Eventually, studies showed that DNA decreases in length when regions of about 166 base pairs wrap like twine around small proteins to form complexes known as nucleosomes . A short stretch of non-wound DNA falls between each nucleosomal unit, the result looking a bit like a string of beads. In such a configuration, a 1-meter (3-foot) strand of DNA is reduced to 14 cm (about 6 inches). This shortened strand then coils even more, until an X-shaped chromosome in a dividing cell measures roughly 1/10,000 the length of the DNA strand it contains!

The “fractal globule” (aka ramen noodles)

So what does the 3-dimensional model of the nucleus, as seen in the Genome Ball, have to do with all this?

 

One of the most important discoveries in genome biology has been the demonstration that genomes are non-randomly organized in the nucleus.

Even though chromatin looks like long straggly threads, it is amazingly well organized: Thanks to the organized coiling of chromatin, genes are able to interact with the DNA regions that regulate them.

The genome is organized into “distinct regions of open and closed chromatin regulatory domains,” explains Dr. Laura Elnitski, senior investigator at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health. Put more simply, chromatin that is less active in a given cell type, or chromosomes containing few genes, are located just inside the nuclear membrane; but more active chromatin (for example, a gene coding for insulin in healthy pancreatic cells), and chromosomes carrying many genes, occupy the center of the nucleus. Overall, the nuclear location of specific genes correlates with their activity in a given cell.

Erez Aiden (who spearheaded the Genome Ball project) also discussed chromatin organization in his prize-winning essay in Science: “Loci on the same chromosome – even at opposite ends – interact more than loci on different chromosomes.” And within individual chromosomes, “open [active] chromatin interacts more with open chromatin and closed with closed,” wrote Aiden. In short:  Genes have more interactions with regions on their own chromosome; and within any given chromosome, active regions group together with other active regions, while quiet or gene-poor areas group with other quiet regions.

Aiden had found a paper theorizing that long polymers – DNA is a good example – are able to form very tight coils with no knots, “a configuration known as the fractal globule.” One of the most striking characteristics of the fractal globule is that it can be folded and refolded without disturbing the rest of the condensed polymer.

 

The fractal globule is easy to explain to graduate students because it closely resembles the only food we can afford: ramen, said Aiden.

Uncooked, the noodles don’t contain any knots. Even when partially cooked, they don’t get tangled in the cooking pan. However, ramen noodles do become tangled after cooking, whereas chromatin stably maintains its unknotted state throughout interphase – the period between cell divisions when chromatin in the nucleus uncoils. In that condensed but non-knotted configuration, sections of chromatin that are far apart on the long strands may be brought into proximity. Thus, interactions between chromatin on the same chromosome, or between sections with similar properties or functions, are made possible by the way chromatin is organized in the interphase nucleus.

These are but a few of the innovative and complex understandings that inspired the creators of the Genome Ball (for more information about the 3-D printing of the Genome Ball displayed at the exhibition, see the feature article “Super 3D Model: How the Genome Ball Was Created” on this website). Our knowledge of the nucleus has come a long way in the 332 years since Leeuwenhoek. But, as Aiden’s Science essay concluded: “at the fringes of our maps the world is full of surprises.”

The same is certainly true of the nucleus.

Source: Unlockinglifescode.org/the-genome-ball. Access November 19, 2017, Genome Project NIH

Resources:

(1) Zoom!” Science 334 (2 December 2011): 1222-1223.

(2) “DNA packaging: Nucleosomes and Chromatin.” Nature Education 1 (2008):26.

(3) “Regulatory and Epigenetic Landscapes of Mammalian Genomes,” Current Topics in Genome Analysis 2014. March 26, 2014.

(4) “Leeuwenhoek Sees the Cell Nucleus.” Science of Aging: Timeline of Discoveries.

(5) Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome. Science 326 (9 October 2009): 189-324.

African Royal DNA Project

Click on the link for more information:
DNA Tested African Descendants and Roots to Glory Tours have partnered to bring you the African Royal DNA Project. This project is designed to assist Africans in the …
www.rootstoglory.com

Journey From Igboland to South Carolina

 

 

 Resource for further information: “The Voyage of the Slave Ship Hare”

I read This article four times to get a feeling for the author and the story. I realized I had transcended home to Igbo land.

Resource: Access August 9, 2017 – https://www.dnatestedafricans.org/single-post/2017/06/18/The-Invisible-Artifact-Something-Amazing-Happened

The Invisible Artifact ~ A Journey From Igboland to South Carolina

April 16, 2017

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AdaaEze Naja Chinyere Njoku

A Dibia (native healer) in Igboland was awakened from a very disturbing dream. The gods were giving him a message. He went to the Eze (king) and informed him. The Eze told him to go and do what he was directed. He returned to the shrine after gathering wood from the sacred Iroko tree. He personally carved a mysterious artifact, creating a secret compartment at the bottom where he placed inside, a kola nut, alligator pepper , and a message.

 


Meanwhile, the Eze summonsed the town crier to have every elder male and elder female of each family to meet him at his palace immediately. They each arrived wondering why they were assembled at such a later hour. The Dibia returned with the artifact and explained that the gods told him of an impending danger.


He said that a tomb will float on the great water, bringing a choking white fog.
The fog would engulf many of the village people but some will survive. He advised
that when this horrible white smoke came, to run to a place near the evil forest
where they would be invisible to the naked eye. A great fear came over the
villagers because no one went near the evil forest unless they were cast out of the
village. It was an abomination.

The elders all began to speak at the same time.


The clanking sound of the Dibia’s staff striking the ground, caused a silence to
roll across the tongues of each person there. His eyes turned a hazy white as he
went into a trance. He said, “Out of this abomination, our people will return”. He
directed each elder to come to the artifact. He recited an incantation and told
each elder to touch a different area of it. When they touched it, that area displayed
a mystical glowing symbol that was not carved into the artifact.

It sealed their DNA into the symbols.

The Dibia explained that the mystical symbols would only glow when a descendant of the elder that touched it was near.


When the last elder touched the artifact, a second seal was placed upon it and another artifact, an exact duplicate appeared out of a puff of red smoke. They were all amazed. He kept the second artifact with him. It could only be passed from Dibia to his successor, until the time of reckoning.


The Dibia called the strongest man in the group. His name was Obinna (Obi). He was noticeable because of the bright spiritual glow about him that only he could see.
 

The guards were given instructions to hold him, regardless to what happened
next. They did. The Dibia placed a green herb in his mouth and pushed the
artifact into his chest. It started to burn his skin as he screamed in uncontrollable
pain. His skin divided and the artifact went inside of him. Then the pain was
gone as if nothing happened. Eze assigned him warriors to guard him day and
night. They were all sworn to secrecy to NEVER reveal what took place that night.

 

About 7 years later, the dreaded tomb came floating on the great water. The white
fog rolled all around it. Many were taken away in the fog while some made it
safely to the meeting place. A mother screamed in the darkness. She was unable
to find her son Obi. He was the one that the Dibia chose to hold the sacred
artifact inside of him.


 

Three Months on the Great Wata
 


The white fog took him and many others to a foreign land. Obinna (Obi) and those that
were with him in that dreadful tomb were placed on a block and sold into slavery.
Obi lived to be 97 years old. He had many children and grandchildren. They called him Papa Obi. They all remembered the stories he told of how he was brought to this place when the white fog came to his homeland. He told them of how he found that some of his age mates decided that they would rather drown themselves than to be enslaved. He even tried himself but the water would not take him. The artifact inside of him caused the water to push him back to the
surface and back away.


His children loved his stories and decided to research this place that seemed almost mythical. They found that it is now called Nigeria. Some call it Naija.  He always said he could still hear his mother’s voice from back home, guiding him, even until the day he died. His body was laid to rest in a beautiful wooden coffin at the foot of a huge tree, in a place now called South Carolina. His tombstone read ” Here lies Obinna, also known as Papa Obi, born 1724 in Nigeria; died 1821 in SC”.

Each year this amazing tree grows closer to its roots and has several knots and bends in it. There is no other tree like it in the whole land.  Some folks call it an angel oak tree.  Others call it a Spirit tree.  There has always been something different about that tree.

 


275 years later, in Nigeria….2016

A Dibia is awakened from a dream. He performed an incantation and retrieved
the artifact. He took it to the Eze and explained its history. The elders of each
family were called to witness the extraction of the message and the Kola nut. The
message read ““Out of this Obama Nation, our people will return. Obi is Ibo, SC”.
It was a peculiar message.


Several scholars, at the University, were called to try to decipher its meaning. It
was baffling. A Nigerian private investigator, named Emeka, was also contacted.
He was preferred because he was aware of the modern day technology as well as
the ancient customs of his people.


When Emeka was taken to see the artifact, one of the symbols glowed. It was a
tree with the letters SC at the bottom of the tree. He found that Obinna and he
shared the same ancestor. They were family! This investigation became a
personal journey. His family was taken by the white fog. Many questions
consumed him. Where are they now? What happened to them? Emeka had to
know.

His Journey to South Carolina began …

Read more by clicking on the link: https://www.dnatestedafricans.org/single-post/2017/06/18/The-Invisible-Artifact-Something-Amazing-Happened
 
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