Genetic Variations Elucidate Origins of Man
September 21, 2012

New Studies On Genetic Variations Offer Insights Into Origins Of Man

April Flowers for - Your Universe Online

Thousands of years ago, a genetic mutation occurred which might be the answer to how early humans were able to move from central Africa and across the continent. This movement has been called "the great expansion."

Three teams of researchers, from Wake Forest Baptist Medical Center, Johns Hopkins University School of Medicine and University of Washington School of Medicine, have analyzed genetic sequence variation patterns in different populations around the world. Their research, published this week in the online journal PLoS One, demonstrates that about 85,000 years ago, a critical genetic variant arose in a key gene cluster on chromosome 11, known as the fatty acid desaturase cluster (FADS).

This genetic variant would have allowed humans to convert plant-based polyunsaturated fatty acids (PUFAs) to brain PUFAs. The long-chain of PUFAs found in the brain are necessary for increased brain size, complexity and function, and the FADS cluster plays a critical role in determining how effectively medium-chain PUFAs in plants are converted.

According to archeological and genetic studies, Homo sapiens appeared approximately 180,000 years ago. For almost 100,000 years, our early ancestors tended to stay in one location close to bodies of water in central Africa. Scientists have hypothesized that this location was critical because early humans needed large amounts of the long-chain PUFA docosahexaenoic acid (DHA) — commonly found in fish and shellfish — in order to support complex brain function.

"This may have kept early humans tethered to the water in central Africa where there was a constant food source of DHA," explained Dr. Floyd Chilton, director of the Center for Botanical Lipids and Inflammatory Disease Prevention at Wake Forest Baptist.

"There has been considerable debate on how early humans were able to obtain sufficient DHA necessary to maintain brain size and complexity. It's amazing to think we may have uncovered the region of genetic variation that arose about the time that early humans moved out of this central region in what has been called the 'great expansion."

Under the intense pressure of natural section, this new trait was able to spread rapidly throughout the entire Homo sapiens population on the African continent.

"The power of genetics continually impresses me, and I find it remarkable that we can make inferences about things that happened tens of thousands of years ago by studying patterns of genetic variation that exist in contemporary populations," said Dr. Joshua M. Akey from the University of Washington.

The most important result of this conversion was that humans no longer had to rely on just one food source, fish, for brain growth and development. This was particularly important because the genetic variant arose before organized hunting and fishing could have provided more reliable sources of long-chain PUFAs.

The research teams analyzed individuals from two different databases; 1,092 people representing 15 different human populations sequenced as part of the 1000 Genomes Project, and 1,043 individuals from 52 populations sequenced in the Human Genome Diversity Panel. They wanted to investigate the evolutionary forces shaping patterns of genetic variation in the FADS cluster in geographically diverse populations. The scientists focused on the FADS cluster because they already knew that those gene codes for the enzymatic steps in long-chain PUFA synthesis that are the least efficient.

The collaboration of the three groups of internationally recognized scientists from three distinct disciplines — fatty acid biochemistry at Wake Forest Baptist, statistical genetics at Johns Hopkins and population genetics at the University of Washington — made these new finding possible.

The new results build upon previous research of Chilton's done in 2011 that showed how people of African descent have a much higher frequency of the gene variants that convert the plant-based medium-chain omega-6 PUFAs found in cooking oils and processed foods into long-chain PUFAs that cause chronic inflammation. This is one reason why African Americans have much higher rates of hypertension, type 2 diabetes, stroke, coronary heart disease and certain types of cancer than their Caucasian counterparts.

"The current observation provides another important clue as to why diverse racial and ethnic populations likely respond differently to the modern western diet," Chilton said.


Two other studies looking at the genetics of African populations in the sub-Saharan region, where humans are thought to have originated, have revealed that even though the click-language peoples of southern Africa live in close proximity, they belong to two distinct genetic clusters.

The Khoisan, or Bushmen as they are sometimes called, are the world's most genetically diverse people who diverged from other human populations very early in species history.

Both teams were looking at single nucleotide polymorphisms (SNPs) — variations at individual nucleotides between different people — to assess the degree of genetic difference in the DNA of the various populations.

Carina Schlebusch at Uppsala University led the study published in the journal Science, which looked at 2.3 million SNPs from 220 individuals belonging to 11 different southern African populations. Joseph Pickrell at Harvard Medical School led the second study, published in Nature Communications, which examined 565,000 SNPs of 187 individuals belonging to 23 southern and eastern African populations.

The teams were able to identify ancestral relationships by considering the similarities and differences among the SNPs in the various click-speaking peoples. These were compared to patterns from other African populations. The teams' data agrees that the southern African click-speaking peoples, or Khoisan, belong to two genetically differentiated groups. One group is in the north Kalahari, and one in the south. They are thought to have split around 30,000 to 35,000 years ago. The revelation of this genetic divide is raising many questions about how it could have happened.

“It makes you wonder if they became isolated from one another for cultural reasons, or if there was some sort of geographical isolation that led to the differentiation,” says Sarah Tishkoff, a human-origins geneticist at the University of Pennsylvania.

Rasmus Nielsen, an evolutionary geneticist at UC Berkeley, agrees that the environment was probably involved in the split. He says that during the last glacial maximum, Africa was very dry and that might have led to an extended period of smaller population sizes and increased fragmentation.

The Harvard team identified a key time of separation among southern African peoples as well as discovered an ancient genetic relationship between the south and east of the continent. East African hunter-gatherer click language peoples, the Sandawe and the Hadza, derive roughly one-quarter of their genetic heritage from the southern African click-speakers despite being geographically isolated from other Khoisan populations. Pickrell argues that this implies the existence of a link having once existed between these peoples.

This might put to rest a rather heated debate between anthropologists and geneticists about the origins of modern humans. Fossil evidence suggests that modern humans originated in eastern Africa, but genetic studies tend to point to southern Africa. Identifying a genetic link between the two regions may help resolve the issue.

The Uppsala team also stumbled upon several genetic surprises. Some of the genes in the populations they studied seemed to have undergone changes due to natural selection after the two southern-African groups split approximately 30,000 years ago. Many of the communities contain signs of what's called a selective sweep. A selective sweep takes place when a trait shows signs of having ℠swept´ through a population by providing it with an evolutionary advantage. The genes affected involve muscle function and growth, fast muscle performance, bone and cartilage formation and immunity.

Of the two groups, the most southerly, carry evidence for selected changes in two immunity-related genes. The northern group shows no sign of this selection.

There were neural genetic traits as well, two of the five strongest signals were genes associated with neural problems like microcephaly and Alzheimer's. This suggests their normal role is to regulate brain function.

“This signal could be due to this population having early and extensive contact with European colonists and suffering epidemics such as smallpox,” explains Schlebusch.

These genetic selections could also be evidence of the emergence of anatomically modern humans. Anthropologist John Hawks of the University of Wisconsin—Madison says, “They confirm selection on a gene that differs between modern humans and the Neanderthals, RUNX2, which may be involved in the unique physical form of our species relative to archaic humans.”

According to Tishkoff, this is further reason to question whether "these populations were geographically widespread and experienced local adaption to different environments."

Another part of what both teams were searching for is the "birthplace" of modern humans. Unfortunately, neither seems to have found it.

The Uppsala research dates the genetic split between the rest of humanity and the Khoisan around 100,000 years ago, putting them 55,000 years before the next branching, when Central African pygmies appeared. Coincidentally, the time of the appearance of the Central African pygmy seems to be roughly the same time that humans started migrating out of Africa, although it is unknown if this is truly coincidence or if there was a single set of environmental conditions that triggered changes in many human populations at once.

They were unable, however, to trace modern populations back to any one particular region, suggesting that early humans came from highly structured populations where genetic exchange took place between subgroups. Structured populations are distinct groups with very little sharing of genetic material between them, and there is a lot of evidence for this type of population in early Africa.

Conversely, an admixture population is a group of humans that experiences a sudden introduction of material from previously isolated populations. There is also evidence of admixture groups, most pronouncedly in the case of the Bantu, some of Africa's most successful agriculturalists. Some populations that are otherwise old show signs of recent introduction of Bantu DNA, while other groups show sudden influxes of East African DNA.

With both structured and admixture populations present, it is very difficult to determine where in Africa modern humans most likely first appeared.

"It remains unclear whether modern humans originated from a single randomly mating population, or if modern humans emerged from a geographically structured population, potentially exchanging genetic material with archaic humans," the authors conclude.

“The complexity of the South African population is the big story,” says Adam Siepel, a computational biologist at Cornell University.

“It undermines simpler stories trying to pinpoint a single geographic origin of modern humans.”

Tishkoff, agrees that you wouldn´t expect to find the cradle of humanity by looking at the present-day African populations´ evolutionary relationships.

“When you look at modern populations, you see where they live today,” she says. “You don´t know where they were 50,000 or 60,000 years ago.”

Though the precise location of our ancestral birthplace as modern humans may never be found, it seems obvious that we owe much of what we are now to these early African populations, and that more answers will become clear as complete genomic sequencing is done.