Most Harmful Mutations Surviving In People Arose In The Last 10,000 Years
    By News Staff | November 29th 2012 10:30 AM | 3 comments | Print | E-mail | Track Comments

    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. 

    Overall, the researchers predicted that about 81 percent of the single-nucleotide variants in their European samples, and 58 percent in their African samples, arose in the past 5,000 years. Older single- nucleotide variants – first appearing longer than 50,000 years ago – were more frequent in African samples.

    The scientists also noted that mutations affecting genes involved in metabolic pathways – chemical reactions in the body to generate and tap energy – tended not to be weeded out by selective forces. Aberrant metabolism contributes to diabetes, lipid disorders, obesity, and insulin resistance – all common, modern scourges.

    The researchers pointed out that the results illustrate the profound effect recent human evolutionary history has had on the burden of damaging mutations in contemporary populations.

    "The historical details of human protein-coding variation provide practical information for prioritizing approaches to disease gene discovery," Akey said.

    Although the enlarged mutational capacity resulting from population growth has led to a greater incidence of genetic disorders among the world's 7 billion people, there is brighter side to the story.

    Mutations have fostered the great variety of traits seen among modern humans, according to the researchers, who added, "They also may have created a new repository of advantageous genetic variants that adaptive evolution may act upon in future generations."

     Published in Nature.


    This article got me thinking: If the high mutational load being carried through portions of the human gene pool is increasing, this it is likely due to the medical suppression of negative selection.. Medicine and healthy enviroments/lifestyles are increasing our capacity for a greater mutational load. The reprecussions of this could potentially play out as a mass die-off, if there is ever a major event that sufficiently challenges us, or perhaps a mahor decrease in fertility. Likely though, medical genomics will offer a way through this. Interesting stuff...

    My thought was that civilization began some 10K years or so ago. Cities, and the stable environments they produce, might be suppressing selection forces which would otherwise have worked against these negative traits...

    Gerhard Adam
    Without detracting from the original research, this article as little or nothing to do with actual fitness or selection.  It is merely an effort to examine the protein-coding genes [i.e. the minority] to obtain a basic history of such variations.

    Since the study does not address regulatory genes, or epigenetics, or virtually anything else that is associated with the actual expression of such genes, to draw more significant conclusions is unwarranted.  In addition, it is a real stretch to argue that our relatively recent knowledge regarding DNA and genetics is sufficient to have altered human selection pressures when this study is examining the genetics of 5,000-10,000 years ago.  Assuredly whatever "harmful" mutations exist, were there and didn't affect selection long before modern medicine arrived on the scene.
    The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave.
    Note that none of this was examined.
    “Most of the changes that affect disease don’t lie in the genes themselves; they lie in the switches,” said Michael Snyder, a Stanford University researcher for the project, called Encode, for Encyclopedia of DNA Elements.
    Mundus vult decipi