Most Harmful Mutations Surviving In People Arose In The Last 10,000 Years
2012-11-29 0:00

From: Science 2.0

Evolutionarily speaking, most of the harmful mutations that still exist in people are recent, which makes the case that nature is still out to get us, even in modern times.

A study dated the age of more than 1 million single-letter variations in the human DNA code and revealed that 86 percent of the harmful protein-coding mutations of this type arose in humans just during the past 5,000 to 10,000 years. These kinds of mutations change one nucleotide – an A, C, T or G – in the DNA sequence.

Some of the remaining mutations of this nature may have no effect on people and a few might be beneficial, according to the researchers. Each specific mutation is rare and they suggest that the human population acquired a lot of these single-nucleotide genetic variants in a relatively short time.

To place this discovery in the context of the prehistory and ancient history of people, humans have been around for roughly 100,000 years. In the Middle East, cities formed nearly 8,500 years ago, and writing was used in Mesopotamia at least 5,500 years ago.

The researchers assessed the distribution of mutation ages by re-sequencing 15,336 protein-coding genes in 6,515 people. Of them, 4,298 were of European ancestry, and 2,217 were African.

"The spectrum of human diversity that exists today is vastly different than what it was only 200 to 400 generations ago," said Dr. Joshua Akey, associate professor of genome sciences at the University of Washington in Seattle. He is one of several leaders of a multi-institutional effort among evolutionary geneticists to date the first appearance of a multitude of single nucleotide variants in the human population.

The researchers based their explanation for the enormous excess of rare genetic variants in the present-day population on the Out-of-Africa model of the human diaspora to other parts of the world.

"On average, each person has about 150 new mutations not found in either of their parents," Akey said. "The number of such genetic changes introduced into a population depends on its size."

Larger populations, continuing to multiply by producing children, have more opportunities for new mutations to appear. The number of mutations thereby increases with accelerated population growth, such as the population explosion that began 5,115 years ago.

During the Out of Africa migration of some early humans into Europe and beyond some 50,000 years past, a population bottleneck occurred: The number of humans plummeted, and the shrinking remnant became more genetically similar. Back then, mutations that were only slightly damaging had a greater probability of being carried from one generation to the next, Akey explained.

"Those mutations don’t influence the ability to survive and reproduce," he said. "The Out of Africa bottleneck led to inefficient purging of the less-harmful mutations."

They found that, compared to Africans, people of European descent had an excess of harmful mutations in essential genes, which are those required to grow to adulthood and have offspring, and in genes linked to Mendelian, or single-mutation diseases. The study team also observed that the older the genetic variant, the less likely it was to be deleterious. In addition, certain genes, they learned, harbored only younger, more damaging, mutations that surfaced less than 5,000 years ago. These include 12 genes linked to such diseases as premature ovarian failure, Alzheimer’s, hardening of the heart arteries, and an inherited form of paralysis.


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