Gene Mutations Began Showing Up In Last 5,000 Years Of Human Evolution

Lawrence LeBlond for – Your Universe Online

In a world that´s more than 4 billion years old, humans have only existed for a fraction of that–roughly 200,000 years. In those 200,000 years of existence, not a lot is known about genetic mutation until we close in on the last 5 to 10 thousand years. It is within that time that researchers believe nearly 75 percent of gene mutations have occurred, making our DNA distinctly different now than it was way back when.

This finding has been calculated in new research from the University of Washington, published in this week´s issue of the journal Nature. The results, based on a genetic study of roughly 6,500 Americans (4,298 European-Americans and 2,217 African-Americans), were gleaned from studying 1 million single-letter variations in the human DNA code. These variations revealed that most of the mutations seen are of recent origin. And more than 86 percent of the harmful protein-coding mutations found occurred during the past 10 millennia. In all, about 14 percent of mutations identified were found to be harmful.

While the researchers found instances of harmful mutations, most were benign and had no effect on people, and a few more may even be beneficial. While each specific mutation is rare, the findings of the study suggest that the human population acquired abundance of single-nucleotide genetic variants in a relatively short time.

“Recent human history has profoundly shaped patterns of genetic variation present in contemporary populations,” study researcher Joshua Akey, of the University of Washington, told Business Insider in an email. “Our results suggest that ~90% of evolutionary deleterious variants arose in the last 200-400 generations.”

Akey said the expanding human growth in population has enabled DNA errors to occur more abruptly. He noted that people with European ancestry have shown the most of these new deleterious mutations because the population boom was more recent among Europeans, and natural selection has yet to remove them.

“There´s an enormous amount of recently arisen, rare mutations that´s directly attributable to the explosive population growth over the last two to four generations,” Akey told Business Week´s Elizabeth Lapatto in a phone interview.

The population of the planet has just soared beyond 7 billion, according to US Census Bureau data. That´s nearly triple the 1950 population of 2.5 billion. Such a rapid increase in population could allow unusual combinations of gene mutations to affect more people albeit remaining relatively rare, Akey said.

While some mutations are seen in the lettering of our genes, other mutations change the way the proteins made from those genes act. Some of these deleterious mutations can have negative impacts on humans’ ability to survive and reproduce, while others could be evolutionary fodder for improving the human race.

“Each generation, humanity incurs on the order of 10^11 new mutations,” Akey said. “The vast majority of these either have no phenotypic or functional consequences, or are deleterious. However, a small fraction are expected to be advantageous [sic].”

“What specific traits they may influence would just be pure speculation, but we can reasonably posit they exist and will be potential substrates for natural selection to act on in the future,” Akey wrote.

Akey added that as the population continues to balloon, so too will new mutations. The growing population makes it more likely that new mutations will be introduced, such as those linked to autism, leading to an increase in other diseases.

The study´s findings are also consistent with the “out of Africa” theory of human evolution, which explains that modern humans emerged in Africa before spreading across the world, according to researchers.

Eric Topol, a professor of translational genomics at the Scripps Research Institute in La Jolla, California, said events such as the Black Death, a plague that wiped out nearly a third of the European population, could be seen through their effects on the genome. He added that today´s data could provide other hints of how the human population expanded, much like tree rings can provide records of past weather.

“This helps us understand bottlenecks and how humans evolved,” said Topol, who wasn´t involved in the study. Now when scientists see new genes or mutations, they “can also begin to ask when did they crop up,” he said.

The data garnered from such studies may also help doctors identify the genetic basis of disease, he said. Researchers tend to look for frequent variations in common ailments, such as diabetes and heart disease. The results from this new study suggest rare variants occur so often that they contribute to common illnesses more than once thought.

In the past, scientists have not been able to detect increasing mutations. This is because past studies have relied on smaller samplings, and also population changes have occurred so rapidly.

Now, because of larger sampling, scientists know much more about these mutations. For instance, it is known from skeletons that humans have grown much larger over the past 1,000 years, a finding that was not detectable in smaller analyses of the exome, the part of the genome that codes proteins.

“It turns out the reason we couldn´t see it before is because the growth happened so recently that you need thousands to see it,” Akey said. “There´s a massive signature of growth.”

He explained that, “on average, each person has about 150 new mutations not found in either of their parents“¦The number of such genetic changes introduced into a population depends on its size.”

He said that as populations continue to multiply, there exists more opportunities for new mutations to appear. The number of mutations thereby increases with accelerated population growth, such as the population explosion that began roughly 5,000 years ago.

In the study, Akey and colleagues found that, compared to Africans, people of European descent had an excess of harmful mutations in essential genes–those required to grow to adulthood and have offspring–and in genes linked to Mendelian (single-mutation disease).

The team also observed that the older the genetic variant was, the less likely it was to be deleterious. They also learned that certain genes harbored only younger, more damaging mutations that surfaced less than 5,000 years ago. These include 12 genes linked to diseases such as premature ovarian failure, Alzheimer´s, hardening of the arteries and inheritable paralysis.

The study also led to researchers predicting that about 81 percent of the single-nucleotide variants in European samples, and 58 percent in African samples, arose in the past 5,000 years. They further found that older single-nucleotide variants–those first appearing more than 5,000 years ago–were most prevalent in African samples.

Akey and colleagues point out that the study results highlight the profound effect recent human evolutionary history has had on the burden of damaging mutations in contemporary populations.

Although the rapid population growth has triggered an onslaught of new gene mutations and greater incidence of genetic disorders, there is a bright side to this story, according to the researchers. Genetic mutations have fostered a great variety of traits in modern humans. “They also may have created a new repository of advantageous genetic variants that adaptive evolution may act upon in future generations,” the team said.

The project, which began in 2008, was funded by the National Heart, Lung and Blood Institute. The work stems from collaboration among numerous genome scientists, medical geneticists, molecular biologists and biostatisticians at the University of Washington, University of Michigan, Baylor College of Medicine, the Broad Institute at MIT and Harvard, and the Population Genetics Working Group.