Sunday, January 24, 2010

PNAS Article of Our Genetic Future

The latest issue of PNAS has this fascinating article on the consequences of human mutations. If we don't develop new genetic interventions, then the populations of industrialized societies will experience a substantial reduction in human fitness due to the rise of deleterious-mutation accumulation.

Critics of new genetic interventions typically invoke the precautionary principle as a reason to not tamper with our genes. But what these critics fail to realize is that our lifestyle and reproduction decisions have already "tampered with" the gene pool. And this article suggests that the status quo is leading us to a dire situation (the solution to which will require new genetic interventions). This particular passage caught my eye:

At least in highly industrialized societies, the impact of deleterious mutations is accumulating on a time scale that is approximately the same as that for scenarios associated with global warming—perhaps not of great concern over a span of one or two generations, but with very considerable consequences on time scales of tens of generations. Without a reduction in the germline transmission of deleterious mutations, the mean phenotypes of the residents of industrialized nations are likely to be rather different in just two or three centuries, with significant incapacitation at the morphological, physiological, and neurobiological levels.

Here is the abstract:

Although mutation provides the fuel for phenotypic evolution, it also imposes a substantial burden on fitness through the production of predominantly deleterious alleles, a matter of concern from a human-health perspective. Here, recently established databases on de novomutations formonogenic disorders are used to estimate the rate and molecular spectrum of spontaneously arising mutations and to derive a number of inferences with respect to eukaryotic genome evolution. Although the human per-generation mutation rate is exceptionally high, on a per-cell division basis, the human germline mutation rate is lower than that recorded for any other species. Comparison with data from other species demonstrates a universal mutational bias toward A/Tcomposition,andleads to thehypothesis that genome-wide nucleotide composition generally evolves to the point at which the power of selection in favor of G/C is approximately balanced by the power of random genetic drift, such that variation in equilibrium genome-wide nucleotide composition is largely defined by variation inmutation biases.Quantification of the hazards associated with introns reveals that mutations at key splicesite residues are a major source of human mortality. Finally, a consideration of the long-term consequences of current human behavior for deleterious-mutation accumulation leads to the conclusion that a substantial reduction in humanfitness can be expected over the next few centuries in industrialized societies unless novel means of genetic intervention are developed.

And one last sample from the article:

Innovations spawned by agriculture, architecture, industrialization, and most notably a sophisticated health care industry have led to a dramatic relaxation in selection against mildly deleterious mutations, and modern medical intervention is increasingly successful in ensuring a productive lifespan even in individuals carrying mutations with major morphological, metabolic, and behavioral defects. The statistics are impressive. For example, fetal mortality has declined by approximately 99% in England since the 1500s (52), and just since 1975, the mortality rate per diagnosed cancer has declined by approximately 20% in the United States population (53). Because most complex traits in humans have very high heritabilities (54), the concern then is that unique aspects of human culture, religion, and other social interactions with well intentioned short-term benefits will eventually lead to the long-term genetic deterioration of the human gene pool. Of course, a substantial fraction of the human population still has never visited a doctor of any sort, never eaten processed food, and never used an automobile, computer, or cell phone, so natural selection on unconditionally deleterious mutations certainly has not been completely relaxed in humans. But it is hard to escape the conclusion that we are progressively moving in this direction.