Two Thirds of European Men Descend From Three Bronze Age Forefathers

Two Thirds of European Men Descend From Three Bronze Age Forefathers

Geneticists from the University of Leicester have discovered that most European men descend from just a handful of Bronze Age forefathers, due to a ‘population explosion’ several thousand years ago.

The project, which was funded by the Wellcome Trust, was led by Professor Mark Jobling from the University of Leicester’s Department of Genetics and the study is published in the prestigious journal Nature Communications.

The research team determined the DNA sequences of a large part of the Y chromosome, passed exclusively from fathers to sons, in 334 men from 17 European and Middle Eastern populations.

This research used new methods for analysing DNA variation that provides a less biased picture of diversity, and also a better estimate of the timing of population events.

This allowed the construction of a genealogical tree of European Y chromosomes that could be used to calculate the ages of branches. Three very young branches, whose shapes indicate recent expansions, account for the Y chromosomes of 64% of the men studied.

Professor Jobling said: “The population expansion falls within the Bronze Age, which involved changes in burial practices, the spread of horse-riding and developments in weaponry. Dominant males linked with these cultures could be responsible for the Y chromosome patterns we see today.”

In addition, past population sizes were estimated, and showed that a continuous swathe of populations from the Balkans to the British Isles underwent an explosion in male population size between 2000 and 4000 years ago.

This contrasts with previous results for the Y chromosome, and also with the picture presented by maternally-inherited mitochondrial DNA, which suggests much more ancient population growth.

Previous research has focused on the proportion of modern Europeans descending from Paleolithic – Old Stone Age – hunter-gatherer populations or more recent Neolithic farmers, reflecting a transition that began about 10,000 years ago.

Dr Chiara Batini from the University of Leicester’s Department of Genetics, lead author of the study, added: “Given the cultural complexity of the Bronze Age, it’s difficult to link a particular event to the population growth that we infer. But Y-chromosome DNA sequences from skeletal remains are becoming available, and this will help us to understand what happened, and when.”

The study ‘Large-scale recent expansion of European patrilineages shown by population resequencing’ is published in Nature Communications.

The DOI for this paper will be 10.1038/ncomms8152. Once the paper is published electronically, the DOI can be used to retrieve the paper by adding it to the following URL: http://dx.doi.org/

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Stem-Cell Scientists Redefine How Blood Is Made, Toppling Conventional ‘Textbook’ View From 1960s

Stem-Cell Scientists Redefine How Blood Is Made, Toppling Conventional ‘Textbook’ View From 1960s

Stem-cell scientists led by Dr. John Dick have discovered a completely new view of how human blood is made, upending conventional dogma from the 1960s.

The findings, published online in the journal Science, prove “that the whole classic ‘textbook’ view we thought we knew doesn’t actually even exist,” says principal investigator John Dick, Senior Scientist at Princess Margaret Cancer Centre, University Health Network (UHN), and Professor in the Department of Molecular Genetics, University of Toronto.

“Instead, through a series of experiments we have been able to finally resolve how different kinds of blood cells form quickly from the stem cell — the most potent blood cell in the system — and not further downstream as has been traditionally thought,” says Dr. Dick, who holds a Canada Research Chair in Stem Cell Biology and is also Director of the Cancer Stem Cell Program at the Ontario Institute for Cancer Research. He talks about the research at http://www.youtu.be/D08FMKDppVQ .

The research also topples the textbook view that the blood development system is stable once formed. Not so, says Dr. Dick. “Our findings show that the blood system is two-tiered and changes between early human development and adulthood.”

Co-authors Dr. Faiyaz Notta and Dr. Sasan Zandi from the Dick lab write that in redefining the architecture of blood development, the research team mapped the lineage potential of nearly 3,000 single cells from 33 different cell populations of stem and progenitor cells obtained from human blood samples taken at various life stages and ages.

For people with blood disorders and diseases, the potential clinical utility of the findings is significant, unlocking a distinct route to personalizing therapy.

Dr. Dick says: “Our discovery means we will be able to understand far better a wide variety of human blood disorders and diseases — from anemia, where there are not enough blood cells, to leukemia, where there are too many blood cells. Think of it as moving from the old world of black-and-white television into the new world of high definition.”

There are also promising implications for advancing the global quest in regenerative medicine to manufacture mature cell types such as platelets or red blood cells by engineering cells (a process known as inducing pluripotent stem cells), says Dr. Dick, who collaborates closely with Dr. Gordon Keller, Director of UHN’s McEwen Centre for Regenerative Medicine.

“By combining the Keller team’s ability to optimize induced pluripotent stem cells with our newly identified progenitors that give rise only to platelets and red blood cells, we will be able develop better methods to generate these mature cells,” he says.

Currently, human donors are the sole source of platelets — which cannot be stored or frozen — for transfusions needed by many thousands of patients with cancer and other debilitating disorders.

Today’s discovery builds on Dr. Dick’s breakthrough research in 2011, also published in Science, when the team isolated a human blood stem cell in its purest form — as a single stem cell capable of regenerating the entire blood system.

“Four years ago, when we isolated the pure stem cell, we realized we had also uncovered populations of stem-cell like ‘daughter’ cells that we thought at the time were other types of stem cells,” says Dr. Dick.

“When we burrowed further to study these ‘daughters’, we discovered they were actually already mature blood lineages. In other words, lineages that had broken off almost immediately from the stem cell compartment and had not developed downstream through the slow, gradual ‘textbook’ process.

“So in human blood formation, everything begins with the stem cell, which is the executive decision-maker quickly driving the process that replenishes blood at a daily rate that exceeds 300 billion cells.”

For 25 years, Dr. Dick’s research has focused on understanding the cellular processes that underlie how normal blood stem cells work to regenerate human blood after transplantation and how blood development goes wrong when leukemia arises. His research follows on the original 1961 discovery of the blood stem cell by Princess Margaret Cancer Centre scientists Dr. James Till and the late Dr. Ernest McCulloch, which formed the basis of all current stem-cell research.

Researchers Reverse Bacterial Resistance to Antibiotics in Lab

Researchers Reverse Bacterial Resistance to Antibiotics in Lab

The rise of antibiotic-resistant bacteria is a growing problem in the United States and the world. New findings by researchers in evolutionary biology and mathematics could help doctors better address the problem in a clinical setting.

Biologist Miriam Barlow of the University of California, Merced, and mathematician Kristina Crona of American University tested and found a way to return bacteria to a pre-resistant state. In research published in the open-access journal PLOS ONE, they show how to rewind the evolution of bacteria and verify treatment options for a family of 15 antibiotics used to fight common infections, including penicillin.

Their work could have major implications for doctors attempting to keep patient infections at bay using “antibiotic cycling,” in which a handful of different antibiotics are used on a rotating basis.

“Doctors don’t take an ordered approach when they rotate antibiotics,” Barlow said. “The doctors would benefit from a system of rotation that is proven. Our goal was to find a precise, ordered schedule of antibiotics that doctors could rely on and know that in the end, resistance will be reversed, and an antibiotic will work.”

Dangers of Antibiotic Resistance

When bacteria grow powerful enough that antibiotics no longer work, it can be a matter of life and death. Recently, at the Ronald Reagan UCLA Medical Center, two people died and seven were injured when a medical scope used in patient procedures harbored drug-resistant bacteria. In the U.S. annually, more than 2 million people get infections that are resistant to antibiotics and at least 23,000 people die as a result, according to the Centers for Disease Control and Prevention.

Resistance to antibiotics is a natural part of the evolution of bacteria, and unavoidable given the many types of bacteria and the susceptibility of the human host. To compensate for bacterial evolution, a doctor fighting infections in an intensive care unit may reduce, rotate or discontinue different antibiotics to get them to be effective in the short term.

The researchers — from UC Merced, AU and UC Berkeley — have been leading the way to uncover how to reverse resistance in the drug environment. They’ve done so by combining lab work with mathematics and computer technology.

“We have learned so much about the human genome as well as the sequencing of bacteria,” Crona said “Scientists now have lots and lots of data, but they need to make sense of it. Mathematics helps one to draw interpretations, find patterns and give insight into medical applications.”

Challenging Work Yields Important Results

After creating bacteria in a lab, the researchers exposed them to 15 different antibiotics and measured their growth rates. From there, they computed the probability of mutations to return the bacteria to its harmless state using the aptly named “Time Machine” software.

Managing resistance in any drug environment is extremely difficult, because bacteria evolve so quickly, becoming highly resistant after many mutations. To find optimal cycling strategies, the researchers tested up to six drugs in rotation at a time and found optimal plans for reversing the evolution of drug-resistant bacteria.

“This shows antibiotics cycling works. As a medical application, physicians can take a more strategic approach,” Crona said. “Uncovering optimal plans in antibiotics cycling presents a mathematical challenge. Mathematicians will need to create algorithms that can deliver optimal plans for a greater amount of antibiotics and bacteria.”

The researchers hope to next test the treatment paths in a clinical setting, working with doctors to rotate antibiotics to maximize their efficacy.

“This work shows that there is still hope for antibiotics if we use them intelligently,” Barlow said. “More research in this area and more research funding would make it possible to explore the options more comprehensively.”