L'aiuto della Genetica

Using modern human genetics to study ancient phenomena 



Anthropology, Breakingnews, Genetics, Human Evolution 


We humans are obsessed with determining our origins, hoping to reveal a little of  “who we are” in the process. 

It is relatively simple to trace one’s genealogy back a few generations, and there are many companies and products offering such services. 

But what if we wanted to trace our origins further on an evolutionary timescale and study human evolution itself? In this case, there are no written records and censuses. Instead, the study of human evolution has so far relied heavily on fossil specimens and archaeological finds. 
Now, genetic tools and approaches are frequently used to answer evolutionary questions and reveal patterns of divergence that reflect different selective pressures and geographical movement. 
This is particularly true for studies of human migrations out of Africa, global population divergence, and its consequences for human health. 

Figure 1. Diagrammatic representation of the serial founder effect model  

[Credit: Emma Whittington] 

Humans Originated in Africa

The current best hypothesis suggests anatomically modern humans (AMH) arose in East Africa approximately 200,000 YBP (Years Before Present). 
AMH migrated from Africa around 100,000-60,000 years ago in a series of dispersals that expanded into Europe and Asia between 60,000 and 40,000 YBP. 
It has been scientifically proven that East Africa is the origin of humans, and supported by both archaeological and genetic data. 
Genetic diversity is greatest in East Africa and decreases in a step-wise fashion from the equator in a pattern reflecting sequential founder populations and bottlenecks. 



Figure 1 shows three populations with decreasing genetic diversity (represented by the colored circles) from left to right. The first population, with the greatest genetic diversity, represents Africa. A second population is shown migrating away from ‘Africa’ taking with it a sample of the existing genetic diversity. This forms the founding population for the next series of migrations. Each time a population migrates it represents only a sample of genetic variation existing in its founding population, and in doing so, sequential migration (such as those in Figure 1) leads to a reduction in genetic diversity with increasing distance from the first population. 

Leaving Africa – Where do we go from here? 

Although the location of human origin is generally accepted, there is a lack of consensus around the migration routes by which AMH left Africa and expanded globally. 
There are many studies using genetic tools to identify likely migration routes, one of which is a recent PLOS One article by Veerappa et al (2015). 
In this study, researchers characterized the global distribution of copy number variation, which is the variation in the number of copies of a particular gene, by high resolution genotyping of 1,115 individuals from 12 geographic populations, identifying 44,109 copy number variants (CNVs). 
The CNVs carried by an individual determined their CNV genotype and by comparing CNV genotypes between all individuals from all populations, the authors determined similarity and genetic distance between populations. 

The phylogenetic relationship between populations proposed a global migration map (Figure 2), in which an initial migration from the place of origin, Africa, formed a second settlement in East Asia, which is similar to a founding population seen in Figure 1. 

At least five further branching events took place in the second settlement, forming populations globally. The migration routes identified in this paper largely support those already proposed, but of particular interest this paper also proposes a novel migration route from Australia, across the Pacific, and towards the New World (shown in blue in Figure 2).

Figure 2. A global map showing CNV counts and possible migration routes  

[Credit: Veerappa et al (2015)] 

Global Migration Leads to Global Variation As AMH spread across the globe, populations diverged and encountered novel selective pressures to which they had to adapt. This is reflected in the phenotypic (or observable) variation seen between geographically distant populations. 
At the genotype level, a number of these traits show evidence of positive selection, meaning they likely conferred some advantage in particular environments and were consequently favored by natural selection and increased in frequency. 
A well cited example of this is global variation in skin color, which is thought to reflect a balance between vitamin D synthesis and photoprotection (Figure 3). 

Vitamin D synthesis requires UV radiation, and a deficiency in vitamin D can result in rickets, osteoporosis, pelvic abnormalities, and a higher incidence of other diseases. 

At higher latitudes, where UV radiation is low or seasonal, experiencing enough UV radiation for sufficient vitamin D synthesis is a major concern. 
Presumably, as AMHs migrated from Africa, they experienced reduced levels of UV radiation, insufficient vitamin D synthesis, and severe health problems; resulting in selection for increased vitamin D synthesis and lighter skin pigmentation. 
Consistent with this, a number of pigmentation genes underlying variation in skin color show evidence of positive selection  in European and Asian populations, relative to Africa. 

On the flip side, populations near the equator experience no shortage of UV radiation and thus synthesize sufficient vitamin D; however the risk of UV damage is much greater. Melanin, the molecule determining skin pigmentation, acts as a photoprotective filter, reducing light penetration and damage caused by UV radiation, resulting in greater photoprotection in darkly pigmented skin. 
Selective pressure to maintain dark pigmentation in regions with high UV radiation is evident by the lack of genetic variation in pigment genes in areas such as Africa. 
This suggests selection has acted to remove mutation and maintain the function of these genes.

Figure 3. A map showing predominant skin pigmentation globally  

[Credit: Barsch (2003)]

 Can genetics and human evolution have a practical use in human health? 
Beyond phenotypic consequences, genetic variation between populations has a profound impact on human health. 
It has a direct influence on an individual’s predisposition for certain conditions or diseases. For example, Type 2 diabetes is more prevalent in African Americans than Americans of European descent. 
Genome wide association studies (GWAS) analyze common genetic variants in different individuals and assess whether particular variants are more often associated with certain traits or diseases. 
Comparing the distribution and number of disease-associated variants between populations can assess if genetic risk factors underlie disparities in disease susceptibility. In the case of Type 2 diabetes, African Americans carry a greater number of risk variants than Americans of European descent at genetic locations (loci) associated with Type 2 diabetes. 
It is clear that an individual’s ethnicity affects their susceptibility and likely reaction to disease, and as such should be considered in human health policy. 
Understanding the genetic risk factors linking populations and disease can identify groups of individual at greater risk of developing certain diseases for the sake of prioritizing treatment and prevention. 
Applying modern human genetics to human evolution has opened a door to studying ancient evolutionary phenomena and patterns. 
This area not only serves to quench the desire to understand our origins, but profoundly impacts human health in a way that could revolutionize disease treatment and prevention. 

In this blog, I have given a brief overview of how using genetic approaches can tell us a great deal about human origins, migration and variation between populations. 
In addition, I have outlined the complex genetic underpinnings behind ethnicity and disease susceptibility, which suggests an important role for population genetics in human health policy. 
This blog post covers only a fraction of the vast amount of ongoing work in this field, and the often ground breaking findings. 
It is unclear exactly how far genetics will take us in understanding human evolution, but the end is far from near. The potential for genetics in this field and broader feels limitless, and I for one am excited by the prospect. 

Author: Emma Whittington | Source: PLOS Blogs [August 01, 2015]

Interdisciplinarietà II

 Un'interessante ed articolata postilla al precedente 'Elogio 

dell'Interdisciplinarietà', con accluse carte geografiche ad 

illustrare gli ipotetici percorsi.  


Out of Africa: 

Did humans migrate quickly and all-at-once 

or in phases based on weather? 


  Considerable debate surrounds the migration of human populations out of Africa. 
Two predominant hypotheses concerning the timing contrast in their emphasis on the role of the Arabian interior and its changing climate. 

In one scenario, human populations expanded rapidly from Africa to southern Asia via the coastlines of Arabia approx. 50,000 to 60,000 years ago. 

Another model suggests that dispersal into the Arabian interior began much earlier (approx. 75,000 to 130,000 years ago) during multiple phases, when increased rainfall provided sufficient freshwater to support expanding populations. 

Early Homo sapiens, known from fossils found at Omo and Herto in Ethiopia, began  making stone tools in the Nile Valley of Egypt some 150,000 years ago.

Previous studies have  traced their path out of Africa through Sinai to the Levant. 

New research reveals a second,  more southerly route through Arabia, where modern human populations lingered  for some 50,000 years before migrating north to the Levant [Credit: National Geographic] 

Ash Parton and colleagues fall into the second camp, writing, "The dispersal of early human populations out of Africa is dynamically linked with the changing climate and environmental conditions of Arabia.

Although now arid, at times the vast Arabian deserts were transformed into landscapes littered with freshwater lakes and active river systems.

Such episodes of dramatically increased rainfall were the result of the intensification and northward displacement of the Indian Ocean Monsoon, which caused rainfall to reach across much of the Arabian Peninsula." 

Parton and colleagues present a unique alluvial fan aggradation record from southeast Arabia spanning the past approx. 160,000 years. 
Situated along the proposed southern dispersal route, the Al Sibetah alluvial fan sequence provides a unique and sensitive record of landscape change in southeast Arabia. 

This record is to date the most comprehensive terrestrial archive from the Arabian Peninsula, and provides evidence for multiple humid episodes during both glacial and interglacial periods. 

Map showing location of the study site and extent of bajada system in southeast Arabia,  including other identified sections of the Al Ain fan (UAE—United Arab Emirates)  [Credit: Parton et al.] 

Evidence from the Al Sibetah alluvial fan sequence indicates that during insolation maxima, increased monsoon rainfall led to the widespread activation of drainage systems and grassland development throughout regions that were important for the dispersal of early human populations. Previously, the timing of episodes of increased humidity was largely linked to global interglacials, with the climate of Arabia during the intervening glacial periods believed to be too arid to support human populations. 

Parton and colleagues suggest, however, that periods of increased rainfall were not driven by mid-high latitude deglaciations every ~100,000 years, but by periods of maximum incoming solar radiation every ~23,000 years. 
They write, "The occurrence of humid periods previously identified in lacustrine or speleothem records highlights the complexity and heterogeneity of the Arabian paleoclimate, and suggests that interior migration pathways through the Arabian Peninsula may have been viable approximately every 23,000 years since at least marine isotope state 
(MIS) 6," about 191 thousand years ago.


Source: Geological Society of America [February 20, 2015]

L' Herpes labiale conferma la teoria 'Fuori dall'Africa'

Hitchhiking virus confirms saga of ancient human migration

A study of the full genetic code of a common human virus offers a dramatic confirmation of the "out-of-Africa" pattern of human migration, which had previously been documented by anthropologists and studies of the human genome.

World map featuring the geographic location of the 6 HSV-1 clades with respect to human migration. The phylogenetic data supports the “out of Africa model” of human migration with HSV-1 traveling and diversifying with its human host. Each clade is depicted by a roman numeral inside a circle. Land migration is depicted by yellow lines and air/sea migration is shown by the pink line [Credit: Aaron W. Kolb, Cécile Ané, Curtis R. Brandt. Using HSV-1 Genome Phylogenetics to Track Past Human Migrations. PLoS ONE, 2013; 8 (10): e76267 DOI: 10.1371/journal.pone.0076267]

The virus under study, herpes simplex virus type 1 (HSV-1), usually causes nothing more severe than cold sores around the mouth, says Curtis Brandt, a professor of medical microbiology and ophthalmology at UW-Madison. Brandt is senior author of the study, now online in the journal PLOS ONE.

When Brandt and co-authors Aaron Kolb and Cécile Ané compared 31 strains of HSV-1 collected in North America, Europe, Africa and Asia, "the result was fairly stunning," says Brandt.

"The viral strains sort exactly as you would predict based on sequencing of human genomes. We found that all of the African isolates cluster together, all the virus from the Far East, Korea, Japan, China clustered together, all the viruses in Europe and America, with one exception, clustered together," he says.

"What we found follows exactly what the anthropologists have told us, and the molecular geneticists who have analyzed the human genome have told us, about where humans originated and how they spread across the planet," said Curtis Brandt.

Geneticists explore how organisms are related by studying changes in the sequence of bases, or "letters" on their genes. From knowledge of how quickly a particular genome changes, they can construct a "family tree" that shows when particular variants had their last common ancestor.

Studies of human genomes have shown that our ancestors emerged from Africa roughly 150,000 to 200,000 years ago, and then spread eastward toward Asia, and westward toward Europe.

Scientists have previously studied herpes simplex virus type 1 by looking at a single gene, or a small cluster of genes, but Brandt notes that this approach can be misleading. "Scientists have come to realize that the relationships you get back from a single gene, or a small set of genes, are not very accurate."

The PLOS ONE study used high-capacity genetic sequencing and advanced bioinformatics to analyze the massive amount of data from the 31 genomes.

"Our results clearly support the anthropological data, and other genetic data, that explain how humans came from Africa into the Middle East and started to spread from there."

The technology of simultaneously comparing the entire genomes of related viruses could also be useful in exploring why certain strains of a virus are so much more lethal than others. In a tiny percentage of cases, for example, HSV-1 can cause a deadly brain infection, Brandt notes.

"We'd like to understand why these few viruses are so dangerous, when the predominant course of herpes is so mild. We believe that a difference in the gene sequence is determining the outcome, and we are interested in sorting this out," he says.

For studies of influenza virus in particular, Brandt says, "people are trying to come up with virulence markers that will enable us to predict what a particular strain of virus will do."

The researchers broke the HSV-1 genome into 26 pieces, made family trees for each piece and then combined each of the trees into one network tree of the whole genome, Brandt says. "Cécile Ané did a great job in coming up with a new way to look at these trees, and identifying the most probable grouping." It was this grouping that paralleled existing analyses of human migration.

The new analysis could even detect some intricacies of migration. Every HSV-1 sample from the United States except one matched the European strains, but one strain that was isolated in Texas looked Asian. "How did we get an Asian-related virus in Texas?" Kolb asks. Either the sample had come from someone who had travelled from the Far East, or it came from a native American whose ancestors had crossed the "land bridge" across the Bering Strait roughly 15,000 years ago.

"We found support for the land bridge hypothesis because the date of divergence from its most recent Asian ancestor was about 15,000 years ago. Brandt says. "The dates match, so we postulate that this was an Amerindian virus."

Herpes simplex virus type 1 was an ideal virus for the study because it is easy to collect, usually not lethal, and able to form lifelong latent infections. Because HSV-1 is spread by close contact, kissing or saliva, it tends to run in families. "You can think of this as a kind of external genome," Brandt says.

Furthermore, HSV-1 is much simpler than the human genome, which cuts the cost of sequencing, yet its genome is much larger than another virus that also has been used for this type of study. Genetics often comes down to a numbers game; larger numbers produce stronger evidence, so a larger genome produces much more detail.

But what really jumped out of the study, Brandt says, "was clear support for the out-of-Africa hypothesis. Our results clearly support the anthropological data, and other genetic data, that explain how humans came from Africa into the Middle East and started to spread from there."

The correspondence with anthropology even extends, as before, to the details. In the virus, as in human genomes, a small human population entered the Middle East from Africa. "There is a population bottleneck between Africa and the rest of the world; very few people were involved in the initial migration from Africa," Brandt says. "When you look at the phylogenetic tree from the virus, it's exactly the same as what the anthropologists have told us."

Author: David Tenenbaum | Source: University of Wisconsin-Madison[October 21, 2013]

E' deceduto Martin Bernal,autore di Black Athena

Martin Bernal, 

‘Black Athena’ Scholar, 

Dies at 76

By PAUL VITELLO

Published: June 22, 2013

Martin Bernal, whose three-volume work “Black Athena” ignited an academic debate by arguing that the African and Semitic lineage of Western civilization had been scrubbed from the record of ancient Greece by 18th- and 19th-century historians steeped in the racism of their times, died on June 9 in Cambridge, England. He was 76.

Harvey Ferdschneider

Martin Bernal, who taught at Cornell for almost 30 years.

The cause was complications of myelofibrosis, a bone marrow disorder, said his wife, Leslie Miller-Bernal.

“Black Athena” opened a new front in the warfare over cultural diversity already raging on American campuses in the 1980s and ’90s. The first volume, published in 1987 — the same year as “The Closing of the American Mind,” Allan Bloom’s attack on efforts to diversify the academic canon — made Mr. Bernal a hero among Afrocentrists, a pariah among conservative scholars and the star witness at dozens of sometimes raucous academic panel discussions about how to teach the foundational ideas of Western culture.

Mr. Bernal, a British-born and Cambridge-educated polymath who taught Chinese political history at Cornell from 1972 until 2001, spent a fair amount of time on those panels explaining what his work did not mean to imply. He did not claim that Greek culture had its prime origins in Africa, as some news media reports described his thesis. He said only that the debt Greek culture owed to Africa and the Middle East had been lost to history.

His thesis was this: For centuries, European historians of classical Greece had hewed closely to the origin story suggested by Plato, Herodotus and Aeschylus, whose writings acknowledged the Greek debt to Egyptian and Semitic (or Phoenician) forebears.

But in the 19th century, he asserted, with the rise of new strains of racism and anti-Semitism along with nationalism and colonialism in Europe, historians expunged Egyptians and Phoenicians from the story. The precursors of Greek, and thus European, culture were seen instead as white Indo-European invaders from the north.

In the first volume of “Black Athena,” which carried the forbidding double subtitle “The Afroasiatic Roots of Classical Civilization: The Fabrication of Ancient Greece — 1785-1985,” Mr. Bernal described his trek through the fields of classical Greek literature, mythology, archaeology, linguistics, sociology, the history of ideas and ancient Hebrew texts to formulate his theory of history gone awry (though he did not claim expertise in all these subjects).

The scholarly purpose of his work, he wrote in the introduction, was “to open up new areas of research to women and men with far better qualifications than I have,” adding, “The political purpose of ‘Black Athena,’ is, of course, to lessen European cultural arrogance.”

He published “Black Athena 2: The Archaeological and Documentary Evidence” in 1991, and followed it in 2006 with “Black Athena 3: The Linguistic Evidence.”

Another book, “Black Athena Writes Back,” published in 2001, was a response to his critics, who were alarmed enough by Mr. Bernal’s work to publish a collection of rebuttals in 1996, “Black Athena Revisited.”

One critic derided Mr. Bernal’s thesis as evidence of “a whirling confusion of half-digested reading.” Some were more conciliatory. J. Ray, a British Egyptologist, wrote, “It may not be possible to agree with Mr. Bernal, but one is the poorer for not having spent time in his company.”

Stanley Burstein, a professor emeritus of ancient Greek history at California State University, Los Angeles, said Mr. Bernal’s historiography — his history of history-writing on ancient Greece — was flawed but valuable. “Nobody had to be told that Greece was deeply influenced by Egypt and the Phoenicians, or that 19th-century history included a lot of racial prejudice,” he said in a phone interview Tuesday. “But then, nobody had put it all together that way before.”

The specific evidence cited in his books was often doubtful, Professor Burstein added, but “he succeeded in putting the question of the origins of Greek civilization back on the table.”

Martin Gardiner Bernal was born on March 10, 1937, in London to John Desmond Bernal, a prominent British scientist and radical political activist, and Margaret Gardiner, a writer. His parents never married, a fact their son asserted with some pride in interviews.

“My father was a communist and I was illegitimate,” he said in 1996. “I was always expected to be radical because my father was.”

His grandfather Alan Gardiner was a distinguished Egyptologist.

Mr. Bernal graduated from King’s College, Cambridge, in 1957, earned a diploma of Chinese language from Peking University in 1960 and did graduate work at the University of California, Berkeley, in 1963 and Harvard in 1964. He received his Ph.D. in Oriental studies from Cambridge in 1966 and remained there as a fellow until he was recruited by Cornell.

His other books, which also focused on the theme of intercultural borrowing, were “Chinese Socialism Before 1907” (1976) and “Cadmean Letters: The Westward Diffusion of the Semitic Alphabet Before 1400 B.C.” (1990).

Besides his wife, he is survived by his sons, William, Paul and Patrick; a daughter, Sophie; a stepson, Adam; a half-sister, Jane Bernal; and nine grandchildren.

Mr. Bernal was asked in 1993 if his thesis in “Black Athena” was “anti-European.” He replied: “My enemy is not Europe, it’s purity — the idea that purity ever exists, or that if it does exist, that it is somehow more culturally creative than mixture. I believe that the civilization of Greece is so attractive precisely because of those mixtures.”

A version of this article appeared in print on June 23, 2013, on page A24 of the New York edition with the headline: Martin Bernal, ‘Black Athena’ Scholar, Dies at 76.