Yersinia Pestis and ERAP2

   

The Black Death was the major cause of death in recorded history. Recent research suggests the Black Death has "...placed a significant selective pressure on the human population, changing the frequency of certain immune-related genetic variants and affecting (people) susceptibility to diseases today" The Black Death was caused by the bacteria Yersinia pestis. The disease killed between thirty to sixty percent of Europeans, North Africans and Asians. Dr. Luis Barreiro, Ph.D., Professor of Genetic Medicine at the University of Chicago, and participants in his study, examined ancient DNA samples from bones of over two hundred individuals from London and Denmark, who died before, during and after the plague. By using targeted sequencing for a set of 300 immune-related genes, the scientists discovered four genes that (while depending on variant) either protected against or increased susceptibility to Yersinia pestis. The team concentrated on one gene with a particularly strong association to susceptibility: ERAP2. Furthermore, individuals, who had two copies of one specific genetic variant, dubbed rs2549794, were able to produce full length copies of ERAP2 transcript (Barreiro 2022) Thus, producing more of the functional protein, compared to a different variant that led to a shortened and non-functional ERAP2 transcript. In addition, the research team tested how the rs2549794 variant affected the the ability of living human cells to help fight the plague, concluding microphages that express two copies of the variant were more effective when neutralizing the bacteria Yersinia pestis. It is fascinating to read and understand the significance of the experiment. Having access to ancient DNA and sequencing technologies to observe the unique characteristics of the organisms is captivating. To me, Genetic Medicine is compelling. It is the meeting point of science and human history. Who are we? Where do we come from? Why do we act the way we do? How much of this information can I deduce from my DNA? Those are questions that the methodology, philosophy and history of genetics and medicine urge me to seek answers. 

How Cities are Affecting the DNA of Birds

 

In a recent study, researchers have discovered that birds who live in cities have differences in their DNA when compared to birds who live in the countryside. The populations of great tits in nine popular European cities were examined. Genes involving cognition and various behaviors relating to serotonin were selected and passed down based on the environment they lived in. The behaviors and sleep cycles of the birds living in cities varied from those in the country. To live in a city, birds have to adapt to the light, noise, and air pollution created by these cities. They also need to adapt to living in close proximity to humans. 192 great tits from Malmo, Gothenburg, Madrid, Munich, Paris, Barcelona, Glasgow, Lisbon, and Milan were studied. Blood samples were compared to birds who lived close by in a rural area. Researchers discovered over half a million single-nucleotide polymorphisms. Many genes seemed to be influenced by this city environment. Great tits are found all over Europe and believed to be very similar genetically, but these studies discovered genetic differences based on the location these birds live. Human influence on the behavior of animals has been known, but I find it interesting how rather new modern cities have already influenced the genetic makeup of birds. It would be interesting to see other genetic differences based on location in other animals living in close proximity to humans.

Europe: An Unexpectedly Close-Knit Continent

In research conducted by scientists in California, it was found that Europeans

are more genetically similar to one another than was previously thought. Using

genetic information obtained from 2,257 people across Europe, scientists Peter

Ralph and Graham Coop were able to ascertain that even people as far apart as

UK and Turkey share genetic similarities. This can be traced back to a group of

ancestors that many Europeans share. These ancestors came to the continent 6,500

years ago, which is earlier than previously thought. It is through these shared

ancestors in the not-so-distant past that Europeans across the continent are connected,

and considered “one big family.” This finding, however, is said by researchers to

not mean much in terms of peace between groups. For example, if anti semitic white

supremacists from one country find that they are related to Ashkenazi Jewish people,

it is unlikely that these Anti Semitic people will change their ways just because they

discover that they are related to Ashkenazi Jewish people.



















Although the findings of this research would prove to be surprising to some,

I personally am not surprised by these findings. I’ve heard the theory before

that everyone on Earth is related to everyone through five points of connection,

whether it’s through a friend’s family member, or a friend’s friend’s friend. I have

also heard that many people are the descendents of the Islamic prophet, Muhammed,

including the current queen of England. I have a friend who is a descendent of the

prophet Muhammed, and this would mean that he is related to the queen of England.

If my friend and the queen of England are so close in relation, I find it easy to believe

that the people of Europe are related to one another, and I find it understandable that

although these people are related, bad blood will likely not disappear. Bad relations

between family are easy to come by, after all.

The Plague in Ancient Neolithic Farming Communities

The large population decrease of European Neolithic farming communities had always been a mystery up until a group of researchers discovered a strain of plague found in a the genetic material of a woman in a rural farming area of 5000 years ago.  Another person buried near her also had traces of the strain of plague.  Based on the fact that this plague had reached Northern Europe earlier than the Eurasian migrants (how people originally believed it reached the area), scientists now believe that it developed in the communities by poor sanitation, too many people and animals.  Trade routes allowed for the disease to spread amongst Europe.  Once the Neolithic communities were wiped out, it allowed for the Eurasian migrants to spread out amongst Europe and this changed the genetic makeup of the continent.  After these discoveries, scientists recreated the genome of the ancient plague to dive deeper into how diseases can spread, and how they can disappear or stay prominent.
https://www.cnn.com/2018/12/08/health/ancient-plague-study-scli-intl/index.html
https://www.cell.com/cell/fulltext/S0092-8674(18)31464-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867418314648%3Fshowall%3Dtrue

Dog DNA study maps breeds across the world

Scientists have analyzed 161 breeds of dog's DNA. Over the past 20 years, dogs have been bred to do different things, depending on what they are needed for. Dogs used to be used for hunting and gathering, now there are many hybrid breeds that are available. Dogs origins can be traced to two basic places in the world the United Kingdom or the Mediterranean. Many dogs like the mastiff has not changed genetically over the years. This article was very interesting to read. Dogs are very important in the world and majority of people have them. Now with all these different dog breeds breeding together, this genetic mapping of them will allow us to better understand what dogs are good for what area.

Related Article: http://genome.cshlp.org/content/19/3/500.short

Article: https://www.sciencenews.org/blog/science-ticker/dog-dna-study-maps-breeds-across-world

How Old is Smallpox Really?

     According to research by an international team of researchers Smallpox might have merged way later then we previously thought. Tissue samples were taken from a Lithuanian child mummy that us dated back to the 1600's. It was concluded that the cause of death was smallpox, but not exactly the strain we cause just a hundred years ago. Reconstructing the full RNA sequence of the smallpox virus strain and compared the results to more recent samples. With this information the team was able to make a time line of the smallpox virus and piece together information about the different strands. While looking at the timeline for the diseases the rate of mutations was also studied and their was found to be two major strand groups, and all related back to a simple common ancestor.  With the information uncovered about the common ancestor it was evaluated that smallpox must have not always been such an epidemic. If small pox had been an epidemic for the thousands of years that it has been around researchers would not have been able to find a common ancestor since it would have diverged tremendously over time. 

     This article is extremely fascinating because with a small sample from a mummy that is thousands of years old they were able to make a time line for small pox and better understand how the virus grew and mutated. With more data like this hopefully we can come to better understand how viruses are spreading so rapidly and diverging out of nowhere. With this knowledge we can better understand and develop more vaccines and save thousands of lives.  

For more information on the history of smallpox go to - https://www.cdc.gov/smallpox/history/history.html

Main article: http://blogs.discovermagazine.com/d-brief/2016/12/08/child-mummy-smallpox-timeline/#.WQfiYIn5601 

Genetic History of European Beaver

http://uploads.neatorama.com/wp-content/uploads/2009/06/beaver_pho34.jpg

Link to Article

Further Information

The family Castordae has only two living species left, Castor canadensis, the North American beaver, and Castor fiber, the European beaver. This was not always the case for the Castordae family, but over time only two species survived, and it was a struggle to make it to today. Castor fiber, the European beaver, has recently the topic of research at the University of York, UK and the University of Potsdam, Germany. They wanted to compare and contrast the DNA genomes of the modern day European beaver to it's relatives that have went extinct as far back at 10,000 years. Through the study they looked at 48 DNA samples of extinct beavers ranging rom a few hundred years old to 11,000 years old, and 152 modern day sequences. Their findings show that the beavers can be divided into three groups, the tow main were found in western and eastern Europe, and the third was found in the Danube basin, but went extinct 6,000 years ago. The findings show that the most genetic diversity was in the past when most of the species coexisted, but know the genetic variation is relatively low.

Only the Castor fiber survives, and can be found throughout Europe and into Northern Asia. It is a shame that the genetic diversity was lost along with so many species. In fact the modern European was almost hunted to extinction in the 19th century, with only 1200 left at the lowest population point. The lack of species and interbreeding or the bottleneck of the modern species may have been the culprit to the low genetic variation.  

How the Brown Rat Conquered New York City

The brown rat has managed to populate New York city by the millions, with billions more in other cities across the world. They contaminate crops and food supplied and destroy wires, walls, and cars, while spreading bacteria and disease. However, scientists are not entirely sure as to how Rattus norvegicus became so rampant. Dr. Munshi-South and colleagues finished a study of brown rats that began to answer the question of what is a New York city rat and where did it come from? They found that these rats began spreading slowly for thousands of years, but in the past three centuries they spread much more rapidly. Dr. Munshi-South contacted researchers from around the world and obtained DNA from hundreds of brown rats, from Japan, New Zealand, Brazil, and the Galapagos Islands to name a few,  to compare to that of the rats of NYC. The study revealed that brown rats originated in northern China or Mongolia and fed on wild plants and small animals, until farming in China began, during which rats found a reliable food supply and moved from open plains to farms and villages. The rats then began to expand to other parts of Asia, and eventually west to Europe. It is these rats that are the ancestors of the inhabitants of New York today. As European countries colonized the Western world, they took the rats with them.

Dr. Munshi-South thought that he would find that New York's rats have a mix of genes from ancestors from all over the world, but he found little evidence of genetic mixing in New York or any other city. It seemed that there was not many migrants that arrived and reproduced after a city was already populated with rats. This could be because brown rats are territorial and simply mean, as noted by missing eyes and scars observed by Dr. Mushi-South in many rats. The theory is that the first rats to arrive in a city reproduce rather quickly, so when new rats come along, they are no match for the residents that have already inhabited the city. This is a good thing because it is unlikely that new diseases on new rats can come into a city that is already populated with rats.
Based on the results of the study, I think that we should not take action to eliminate brown rats. Although they do spread bacteria and destroy wires and walls, they are keeping out lots of potential disease because of their territorial nature.

Blood Samples Connected to Malaria's Migration

Spain contained many accounts of malaria in 1925, and Dr. Canicio was specifically interested in this outbreak. He worked with patients and extracted some of their blood, leaving behind samples.  These samples were key to determining the number of strains throughout Europe and how they got there in the first place. 

The samples were recently given to Dr. Lalueza-Fox where he worked specifically with them.  His goal was to gain more factual knowledge about malaria and the strains that were prominent around Europe at that time.  He was able to retrieve genomic data of malaria by reversing a commonly used method.  Dr. Lalueza-Fox searched for DNA in the "leftovers" of the sample and emerged with the parasites that cause malaria.  From his findings, he was able to construct the entire genome of the strain P. falciparum and most of the genome of P. vivax.  His findings were remarkable.  From just a few drops of blood taken about fifty years ago, an entire genome was reconstructed. 

P. vivax, which was found in blood samples from Spain, is found today in areas including Asia, Middle East, South America, Central America, and sections of Africa.  P. falciparum is only found in India.  With this information, conclusions can be made that malaria follows the path of humans.  With people traveling from India to Europe to the Americas, malaria has been consistently with us.

This information builds curiosity about what else can be traced along with the migration of humans. There is no doubt that human movement has caused a transportation and introduction of different species to new areas.  This discovery about malaria has just been made, so what does the future hold?   

Some People 'Hardwired' to Prefer High-Calorie Foods

Dr. Tony Goldstone from Imperial College London in UK and his colleagues have found two genetic variants that seem to influence whether an individual chooses high or low calorie foods. The team conducted DNA genotyping on 45 white European adults ranging from age 19 to 55 in order to identify the presence of the FTO gene, which plays a role in the regulation of dopamine in the brain, the reward hormone. These participants ranged in their body mass from 19.1 kg/m2 to 53.1 kg/m2, ranging from healthy to obese.
The participants were asked to view piectures of high and low calorie foods and rate how appealing they were, and an MRI was used to analyze their brain activity.
It was found that those who posessed some variant near the FTO gene and rated the high calorie foods as more appealing demonstrated greated activity in the orbitofrontal cortex as well as the striatum depending on the DRD@ gene variant they possessed.
They suggest that individuals with the FTO gene may be at a greater risk for obesity early beccause thy experience more cravings than the average person for high calorie foods.
Some treatments have been suggested after this study, such as using gut hormones that target dopamine cells in the brain to alter the hormone's influence on cravings.
The study helps researchers to better understand the biological behaviors that lead to obesity.

Original article

Asians and Europeans; Lactose-Intolerant 5,000 Years Ago

     Studying ancient DNA has always been a big part of genetics as it gives insight into the past history of humans. What was generally already found is that around 5,000 years ago, Europeans and Asians are generally light-skinned and - surprisingly - lactose intolerant. During the Bronze Age, which ranged from the years of 3,000 - 5,000 years ago, was a time of mass human migrations throughout the region of Europe and Asia. Because of these large migrations, the present-day demographic structure has been developed. 

     Researchers have sequenced genomes from 101 unearthed ancient humans from Europe and Asia. Although DNA sequences have previously been studied using ancient DNA, the new technology that is available makes for clearer data. It has recently been discovered by Morten Allentoft of the University of Copenhagen’s Natural History Museum and his colleagues that light-skinned Europeans were present at a high frequency already in the Bronze Age, thus implying that light-skinnedness was first developed previous to 5,000 years ago. Another conclusion from their data tells that during the Mesolithic hunter-gatherer age, the presence of blue eyes was already established. 

     These data are set to answer the question, could there be a greater distribution of Neanderthal DNA in the genomes of Europeans and Asians? This is still unclear, however the findings suggests that these humans were settled into Europe and Asia before the Bronze Age.

     Something also interesting about the data is that 5,000 years ago, humans had not evolved the enzyme to break down lactose - the sugar found in milk. In an evolutionary perspective, this makes sense because ancient humans and - in fact, mammals in general - do not need to drink milk to survive after infancy, thus the lactose intolerance. When humans began to produce the enzyme to break down that indicated the start of domestication of animals which did not occur much before 5,000 years ago thanks to the data. 

     I personally think that this article is interesting because there are people who today are still lactose intolerant. The article tries to explain this as their ancestors did not drink much milk, thus never needing the enzyme to break down lactose. It is amazing how using the preserved DNA from bones that have been under the earth for so long can lead to vast discoveries like this. This discovery tells a lot about the time line of when humans became what we are today.

Original Article

More about the Bronze Age

                                                            Is Europe One Big Family?

Research has been done in order to study the genetic relatedness of European people. It was found that people from the U.K. and Turkey shared a large amount of genetic material. Researchers Peter Ralph and Graham Coop used the genomic data of 2,257 Europeans to represent the continent as a whole. In another study DNA was collected from ancient skeletons and it was discovered that people that these class of DNA came from immigrants that were responsible for the genetic makeup of what we know is Europe today. Ralph and Coop as well as other scientists involved in such studies confirmed that each and every individual on this planet is genetically related, even if it is an extremely small percentage. They did, however, note that the ancestry between different types of Europeans was not equally shared.

The article brings into focus that although all of Europe shares similar genetic material, people classify themselves as different and often hold their own prejudices. Besides their genetic relatedness their views on a different population would not change, and therefore cause people to be skeptical about the results of the research despite the evidence given. In all, I feel that this research has shown that although different nationalities appear to look extremely different from each other and have select features that are common within that nationality, looking at one's raw DNA proves that human beings have a common ancestor. This research serves as further evidence on evolution and how mankind evolved from a common ancestor.

Primary Article: http://rendezvous.blogs.nytimes.com/2013/05/08/genetics-reveal-europe-is-one-big-family/

Secondary Article: http://news.ucdavis.edu/search/news_detail.lasso?id=10557

Ancient DNA Used to Understand Europeans Today

From the beginning of humans venturing out of Africa to different parts of the world changes in genetic composition have occurred. As their environment changed so did their genetic traits, and those who ended up in Europe were no different. Their skin and hair becoming lighter were the most obvious traits to have changed but many other traits also changed and this can be easily observed from looking at living Europeans today.  However, due to the advanced biotechnology which has now recently been harnessed it is possible to extract DNA from bones of Europeans who lived thousands of years ago.

David Reich, a geneticist at Harvard Medical School and his colleagues have analyzed nine genomes of ancient Europeans, eight of which were hunter-gatherers believed to have been living 8,000 years ago, and one farmer who is believed to have lived 7,000 years ago. Comparing the genomes to Europeans living today the researchers revealed Europeans today have genes from three different populations. The oldest population is the first Europeans who were hunters-gatherers, the second being farmers from the near east who expanded into Europe around 8,500 years ago, and the third, surprisingly, from north Eurasia about 7,000 years ago. Most Europeans today carry all three genes. Most exciting of the study is that now there is a timeline created, describing when and how other areas, such as the east, has influenced Europe.

A 7,700-year-old skeleton of a woman found in Hungary has yielded DNA. Scientists have found that she belonged to a wave of early farmers who moved into Europe from the Near East.

This article was particularly interesting to me because I found the results of the European genetics being influenced by the east interesting. Personally I would have thought that it would be the opposite due to Europe’s huge influence on the entire world early in time. I also am always interested in the techniques which can be used to analyze ancient DNA, although this article did not give much information and detail on the process. 

Article: http://www.nytimes.com/2014/10/30/science/from-ancient-dna-a-clearer-picture-of-europeans-today.html?ref=science&_r=0
Related Article: http://www.cam.ac.uk/research/news/ancient-dna-shows-earliest-european-genomes-weathered-the-ice-age-and-shines-new-light-on

Root of Ashkenazi Family Tree

    The origin of an important Jewish population, the Ashkenazim of Central and Eastern Europe has forever been a mystery. A new genetic analysis has been configured, pointing to European women as the female founders, and the Jewish community of the early Roman empire as a source of the Ashkenazi ancestors. In previous studies it was told that the women who founded the Ashkenazi Jewish community were from the Near East, but today's findings express otherwise. A study led by Martin B. Richards of the University of Huddersfield, England, composed a genetic analysis of maternal lineages. The team analyzed the Ashkenazi lineages by decoding the mitochondrial genomes of people from Europe and the Near East. Earlier DNA studies showed that Jewish communities had been founded by men whose Y chromosomes bore DNA patterns found in the Near East. But, unlike the males, when geneticists went to examine the females, their mitochondrial DNA has no common pattern. In the smaller communities it resembled that of the surrounding population, suggesting a migration pattern in which the men arrived single, possibly as traders, and took local wives who converted them to Judaism. But this idea has not been clear as to if this is true or not of the Ashkenazim.
    A 2006 study reported that the four most common mitochondrial lineages among the Ashkenazis came from the Near East, implying that only four Jewish women made up the entire ancestry of about half of today's Ashkenazim. But at the time decoding DNA was expensive and those scientists only analyzed a short length of the DNA. However, in this New York Times article Dr. Richards was able to draw up the Ashkenazi family tree with much finer resolution and more accuracy. His trees showed that the four major Ashkenazi lineages form clusters within descent lines established in Europe between 10,000 and 20,000 years ago. In conclusion, he determined that "at least 80 percent of Ashkenazi maternal ancestry comes from women indigenous to Europe, and 8 percent from the Near East, with the rest uncertain." Richards feels that the four major lineages became incorporated into the Ashkenazi community about 2,000 years ago because at that time a large Jewish community was flourishing in Rome and included many converts. A recent analysis of whole genomes of Jewish communities was noted that almost all overlap with non-Jewish populations. Overall, Richards sees this knowledge as a possible time and place at which the four European lineages could have possibly entered the Jewish community, becoming numerous later as the Ashkenazi population in northern Europe expanded from 25,000 in 1300 A.D., to over 85,000 million in the beginning of the 20th century.

I chose this article to read because I love learning about ancestry. This discovery caught my eye and I feel that new findings in ancestry offer many answers to many questions people may ask. We want to know where we come from and the more we know the more we can express to others.

(Article): http://www.nytimes.com/2013/10/09/science/ashkenazi-origins-may-be-with-european-women-study-finds.html?_r=0


Second Link: http://blog.23andme.com/23andme-customer-stories/ashkenazi-and-me-discovering-unknown-jewish-ancestry-with-23andme/

How was Europe Repopulated After the Ice Age?

Scientists are answering this question through DNA analysis.  During the last Ice Age, most humans were concentrated in two principle areas:  the "Franco-Cantabrian" area, located in curent day northern Spain/southern France, and the "Periglacial province", located in current day Ukranian Plains.  It is generally accepted that humans from these two populations later moved up into Europe to repopulate the area after the Ice Age, nineteen thousand years ago.



Dr. Maria Pala and other scientist from the University of Hudderfield, UK, have analyzed large quantities of mitochondrial DNA from these two groups of humans, whom share a common genetic ancestor.  Their data shows evidence of the two tribes moving into Europe much earlier than previously believed, at the end of the last ice age.  Through this study, the University of Hudderfield has become a key center for archaeo-genetic research.

This research is outlined in the May 2012 issue of the American Journal of Human Genetics.  This is a major breakthrough in the study of archaeo-genetics.  I think this article show the significane of what we can learn from genetic studies, especially about our past.  It is amazing what we can learn from ancient DNA!!!

Bear Hunting Altered Genetics More Than Ice Age Isolation

It was previously believed that the Ice Age, which effected most species twenty thousand years ago, also effected the distribution of bears.  However, recent studies of mitochondrial DNA led by Anders Gotherstam of Sweden, have shown that this is not the case.  In fact, the European Brown Bear was able to roam freely across Southern and Central Europe throughout the Ice Age.



However, these bears no longer live in these regions.  It is believe that this is due to historical hunting and human activity in what would have been the brown bears natural environment.  Today only a few populations of brown bears remain in Spain, Italy, the Balkans, and Scandinavia.

This study was conducted by researches from Sweden, Spain, the UK, Germany, and France.  It was published in the Molecular Ecology journal.  I was surprised that human activity effected the distribution of bears more than the Ice Age did!  It's depressing to know that even twenty thousand years ago humans were already having a negative effect on our environment.

Small Mammals Have a 'Celtic Fringe' Too!

The 'Celtic fringe' is a group of people in the Northern and Western British Isles who are culturally and genetically distinct.  The existence of this 'Celtic fringe' has been debated by scientists for some time now.  New evidence has been found in support of the Celtic fringe theory through the movement of small mammals into Europe after the last Ice Age.  The study analyzed mitochondrial DNA lineages of the bank vole, the field vole, and the pygmy shrew.  This data determined that they colonized Europe in a two-phase process.



This colonization mimics the Celtic human distribution throughout Scotland, Northern Ireland, Eire, Wales, the Isle of Man, and Cornwall.  "We believe this study of the distribution of small mammals can help us to understand why humans in the British Isles form a Celtic fringe," stated Professor Searle of the University of York.  This study was published in Proceedings of the Royal Society B.

I was very interested that these researchers were able to connect genetic similarities between small mammals and the Celtic humans.  I have taken an entire class regarding the history and culture of the Celtic people and find the subject fascinating.  What I learned, however, was based on ancient texts.  I am glad that these small mammals are contributing to the proof of the Celtic existence from a scientific standpoint.