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These children could no longer produce normal hemoglobin. As a result, their red cells became defective and clogged their blood vessels. The condition, now known as sickle cell anemia, leads to extreme pain, difficulty with breathing, kidney failure and even strokes.

In early human societies, most children with sickle cell anemia likely died by age 5. Yet the protection afforded by a single copy of the sickle cell mutation against malaria kept fueling its spread.

Today, over 250 generations later, the sickle cell mutation has been inherited by millions of people. While the majority of carriers live in Africa, many others live in southern Europe, the Near East and India. Those carriers have about 300,000 children each year with sickle cell anemia.

How humans got the sickle cell mutation is a sprawling saga that emerges from new research carried out at the Center for Research on Genomics and Global Health, part of the National Institutes of Health, by Daniel Shriner, a staff scientist, and Charles N. Rotimi, the center's director. Their study was published on Thursday in the American Journal of Human Genetics.

Dr. Shriner and Dr. Rotimi analyzed the genomes of nearly 3,000 people to reconstruct the genetic history of the disease. They conclude that the mutation arose roughly 7,300 years ago in West Africa.

Later, migrants spread the mutation across much of Africa and then to other parts of the world. Wherever people suffered from malaria, the protective gene thrived - but brought sickle cell anemia with it.

Today, sickle cell anemia remains a heavy burden on public health. In many poor countries, most children with the disease still die young. In the United States, the average life span of sufferers has been extended into the early 40s.

Dr. Rotimi said that an improved understanding of the history of sickle cell anemia could lead to better medical care. It might allow researchers to predict who will suffer severe symptoms and who will only experience mild ones.

"It would definitely help physicians to treat patients at a global level," he said.

Doctors in the United States first noticed sickle cell anemia in the early 1900s. The disease got its name from the way it changed the shape of red blood cells from healthy disks to abnormal curves.

Most cases turned up in African-Americans, doctors found. But 8 percent of African-Americans had at least some sickle-shaped blood cells, even though the vast majority had no symptoms at all.

By 1950, researchers had resolved this paradox, discovering the difference between carrying one mutated copy of the hemoglobin gene and carrying two copies. By then it had also become clear that sickle cell anemia was not unique to the United States.

In Africa, researchers found sickle-shaped red blood cells in people across a broad belt, from Nigeria in West Africa to Tanzania in the east. The cells also turned up at high rates in people in parts of the Near East and India, and in southern European countries such as Greece.

Genetically speaking, this made no sense. Because inheriting two copies of the gene is so deadly, the mutation should have become rarer with passing generations, not more common.

In 1954, a South African-born geneticist named Anthony C. Allison observed that people in Uganda who carried a copy of the sickle cell mutation suffered fewer malaria infections than people with normal hemoglobin.

Later research confirmed Dr. Allison's finding. The sickle cell mutation seemed to defend against malaria by starving the single-celled parasite that causes the disease. The parasite feeds on hemoglobin, and so it's possible that it can't grow on the sickle cell version of the molecule.

"Sickle cell is a rare example of human evolution where we have a good idea of what happened and why," said Bridget Penman, a malaria expert at the University of Warwick in England.

Early genetic studies suggested that five different kinds of DNA, known as haplotypes, surround the mutation. These are named for the places where they were most common: Arabian/Indian, Benin, Cameroon, Central African Republic and Senegal.

These haplotypes became important for diagnosing sickle cell anemia, because some appeared to cause more severe disease than others. But the haplotypes also gave scientists a chance to explore the history of the mutation.

"It has been an open question as to whether the actual sickle cell mutation itself emerged several times or just once," said Dr. Penman.

Some researchers saw the five haplotypes as evidence that the mutation arose on five separate occasions in five different places. Other researchers thought it unlikely that genetic lightning could strike so many times.

"We said, 'How do we jump into this forty-year debate?'" said Dr. Rotimi.

He and Dr. Shriner examined the genomes of 2,932 people from around the world. They found that 156 of the subjects - mostly from Africa, but also from Barbados, the United States, Colombia and Qatar - carried a copy of the sickle cell mutation.

The researchers scanned the DNA surrounding the mutation in those people. While most of it was identical from person to person, in some spots it differed.

Combining their findings, the researchers concluded that all 156 people inherited the same mutation from a single person who lived roughly 7,300 years ago. "This alone is a big contribution to our understanding," said Dr. Penman.

The new study also offers hints as to how the mutation spread to millions of descendants.

The oldest version of the sickle cell mutation is found in people from western and central Africa. They may have inherited it from an ancestor in the green Sahara.

The mutation might have spread to other parts of Africa with the expansion of a people called the Bantu. Arising about 5,000 years ago around what is now Cameroon and Nigeria, they converted woodlands to farm fields on a massive scale.

As they cleared land for agriculture, they may have promoted the spread of malaria by mosquitoes. The insects thrived by laying eggs in standing water around the farms and feeding on the growing population of farmers. The intensification of malaria in human populations may also have accelerated the spread of the protective sickle cell mutation.

Over the next few thousand years, the Bantu carried the mutation across much of eastern, central and southern Africa, Dr. Shriner and Dr. Rotimi conclude. In places where malaria was prevalent, the mutation offered protection. But malaria is rarer in southern Africa, and there the sickle cell mutation became rarer, too.

Later, the study suggests, Africans carried the mutation to other parts of the world. Waves of migrants made their way to the Near East. As people from different ancestries interbred, the mutation made its way further afield, into Europe and India.

Some West Africans captured in the slave trade brought the sickle cell mutation to the Americas. But in places like the United States, where malaria was uncommon or nonexistent, the mutation offered less of an evolutionary advantage. As a result, African-Americans have a lower rate of sickle cell anemia than Africans today.

Frederick B. Piel, an epidemiologist at Imperial College London, said he looked forward to bigger genome-based studies on the sickle cell mutation. It remains to be seen if these patterns can be found in thousands of carriers, instead of just 156, he said.

Dr. Penman said that scientists also should study the different genetic variations identified in the new research. These may help explain why the sickle cell mutation leads to deadly symptoms in some people and only mild ones in others - something that scientists still can't explain.

"This knowledge might inspire treatments in itself," she said.

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How One Child's Sickle Cell Mutation Helped Protect the World From Malaria

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These children could no longer produce normal hemoglobin. As a result, their red cells became defective and clogged their blood vessels. The condition, now known as sickle cell anemia, leads to extreme pain, difficulty with breathing, kidney failure and even strokes. In early human societies, most children with sickle cell anemia likely died by age 5.

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In an initial study, the team used master switches in the beetles' genome to manipulate which segments of the body had wings. To their surprise, doing so disrupted portions of anatomy that had seemed unconnected to flight.

This offered some support for the idea that wings were composite tissues. But how might the ancestral wing structures have formed?

The researchers turned their attention to the pupae, which have defensive sets of miniature pincers along their abdomens. These so-called gin-traps sit near the top of the insect, which make them likely models for early wing structures.

To add support for the dual origin hypothesis, Dr. Linz said, evolution would have had to fuse a structure on the dorsal region of the segment and one from the pleural tissue.

The team introduced a fluorescent green protein into the beetles that marked the expression of certain wing-related genes, making it easy to tell which tissues were being affected by genetic tampering. After manipulating genes of the abdomen, they were delighted to see two green tissues: one at the dorsal gin-trap, and one down in the pleural tissue.

And by doing so, they were able to produce pupae in which both tissues fused to form pairs of tiny wings.

"They're obviously very, very sick, because that's not how they normally develop," Dr. Linz said. "They frequently just die, so sadly I was never able to produce an adult beetle with 10 pairs of wings."

While he found the study interesting, Dr. Shockley said the idea that embryonic or larvae development is like a fast-forwarding tape of prior evolutionary modifications has largely been discredited.

Still, he acknowledged that manipulating gene expression is useful for trying to piece together details of structures that are hard to visualize.

"I would like to see if they could get a third pair of wings to express," Dr. Shockley said. "There's been additional debate about whether proto-insects would have actually had three pairs of wings and then lost the first pair, perhaps to deal with aerodynamic instability from three sets of wings beating instead of just two."

The debate about how insect wings evolved is far from over, Dr. Tomoyasu said. "We're still relying on one species," he said. "Although we see that there are two tissues that are contributing to make wings, that could be unique to this lineage."

"It's crucial for us to study more insects," he added. "In my lab, we're now studying cockroaches and some crustaceans to see if the process repeats the same way."

In the meantime, he holds out a bit of hope that the fossil record someday might help solve the mystery.

"We are very confident about our analyses, but it's a prediction," he said. "It would be very cool to actually see the shape of an ancestral insect."

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proceedings of the national academy of sciences

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Insects Flew Before Anything Else Did. So How Did They Get Their Wings?

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In an initial study, the team used master switches in the beetles' genome to manipulate which segments of the body had wings. To their surprise, doing so disrupted portions of anatomy that had seemed unconnected to flight. This offered some support for the idea that wings were composite tissues.

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Paris (France) (AFP) - The risk of cot death may be increased by the presence of a rare genetic mutation which affects breathing muscles, researchers said on Thursday.

The study, published in The Lancet, raises for the first time the possibility of a genetic link to sudden infant death syndrome (SIDS), one of the leading causes of infant mortality.

Carried out by experts in Britain and the United States, the research focused on the SCN4A gene which affects the breathing muscles, thought to play an important role in explaining cot deaths.

Mutations of this gene are typically found in fewer than five people in every 100,000.

In a study of 278 children who died of cot death, researchers found four cases of the mutation, while there were none in a parallel group of 729 healthy controls.

"Our study is the first to link a genetic cause of weaker breathing muscles with sudden infant death syndrome, and suggests that genes controlling breathing muscle function could be important in this condition," said Professor Michael Hanna of MRC Centre for Neuromuscular Diseases at University College London.

"However, more research will be needed to confirm and fully understand this link," said Hanna, one of the authors of the study.

- Not the sole cause -

The gene provides instructions to an important cell surface receptor in the breathing muscles, whose activity is low at birth but which increases over the first two years of life.

Mutations in this gene can cause a range of genetic neuromuscular disorders, as well as life-threatening pauses in breathing and vocal chord spasms that can make breathing temporarily difficult.

SIDS is the unexplained death of a seemingly healthy child within the first year of life, typically affecting babies two and four months old.

It is the leading killer of babies of up to a year, and is said to account for some 2,400 deaths per year in the United States, and around 300 in Britain.

The study only looked at infants of European ancestry, and the authors stressed the need to duplicate the study with other ethnic groups in which the suspect SCN4A mutation may be more or less common.

The gene is almost certainly not the sole cause of death, they said, emphasising that safe sleeping measures were still essential to ensure babies' safety.

Previous research has shown that urging parents to put babies to sleep on their backs helped drive down the death rate in the United States from 120 per 100,000 live births in 1992 to 56 per 100,000 in 2001 -- a 53 percent reduction in one decade.

That advice still stands, the authors said.

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Cot death risk may be heightened by genetic mutation: study

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The risk of cot death may be increased by the presence of a rare genetic mutation which affects breathing muscles, researchers said on Thursday.

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The findings lend support to a disputed conservation strategy called genetic rescue, which involves introducing genetic diversity to boost the survival chances of small, inbred populations, said Jennifer Neuwald, an assistant professor of biology at Colorado State University who was not involved in the new study.

"This study showed that having those new individuals bring in new DNA actually had an effect," she said.

Arctic foxes - which remain abundant in parts of North America and Russia - come in two color morphs. White morphs are snowy in winter and brown-grey in summer, while blue morphs stay a ravishing indigo, brown and charcoal mix year-round.

The blue foxes that arrived in Helagsfjället had come from a captive breeding and restoration program funded by the Norwegian government. In 2009, the program released two blue brothers and another, unrelated white male in southern Norway. The three migrated about 150 miles to the Swedish subpopulation.

Malin Hasselgren, a Ph.D. student in zoology at Stockholm University, led efforts to construct a giant family tree with DNA sampled from 543 foxes, or 105 litters, born in Helagsfjället between 2000 and 2015.

In the five years following the arrival of the new males, the population of the Helagsfjället clan nearly doubled. Over the same period, inbreeding also decreased by 43 percent, which is "really rapid," Ms. Hasselgren said.

Perhaps more important, the first generation of pups born to immigrant fathers was more evolutionarily fit than inbred pups: The former were almost twice as likely to survive their first year of life, and had higher breeding success.

These higher survival and breeding rates help the authors "make the case that a reduction in inbreeding is helping this population grow," said Sarah Fitzpatrick, an assistant professor of integrative biology at Michigan State University not involved in the research.

A larger concern is that the benefits of genetic rescue will be short-lived.

In 1997, a single male wolf immigrated from Canada to Isle Royale in Michigan, causing inbreeding levels to plummet by 89 percent in four years. But then his DNA overtook the entire Isle Royale wolf population, leading to a climb in inbreeding and genetic defects that proved to be devastating. As of this winter, Isle Royale may be down to its last wolf.

Adding new individuals to a threatened population can also introduce disease or swamp local adaptations. Decades ago, conservationists moved some ibexes, a type of wild goat, from the Middle East to mate with a dwindling population in what was then Czechoslovakia. But the resulting hybrids ultimately could not survive the cold, causing the entire population to go extinct.

Still, genetic rescue has had successful outcomes too, for panthers in Florida, bighorn sheep in Montana, vipers in Sweden and others. Many conservationists believe it's a tool with increasing potential, as wildlife populations become more and more fragmented by human activities.

Dr. Neuwald emphasized that the key is "going in with your eyes wide open," by having considered the genetic, ecological and social compatibility between transplants and existing populations.

If that's done, and if genetic rescue gives a species its best chance of survival, "it's worth giving it a try," she said.

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proceedings of the royal society b (journal)

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Arctic Foxes on a Swedish Mountain Turned 'Blue.' It Was a Good Thing.

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The findings lend support to a disputed conservation strategy called genetic rescue, which involves introducing genetic diversity to boost the survival chances of small, inbred populations, said Jennifer Neuwald, an assistant professor of biology at Colorado State University who was not involved in the new study.