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A Billion Genes and Not One Beneficial Mutation

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Natural selection cannot invent things. That’s a fact that Douglas Axe establishes clearly in his new book Undeniable. All improvements must come from random mutations. Think of all the progress from the first microbe to a human body. Every single instance of innovation — large or small — had to originate in what amounts to “blind search” for something good that natural selection could preserve at a moment in time and place. The inability of blind search to locate any benefit in a sufficiently large search space is a topic Dr. Axe discusses at length.

Evolutionists often speak in generalities about beneficial mutations. They may be rare, we are assured, but they happen. And when they do, “natural selection is daily and hourly scrutinising, throughout the world, every variation, even the slightest; rejecting that which is bad, preserving and adding up all that is good; silently and insensibly working, whenever and wherever opportunity offers, at the improvement of each organic being in relation to its organic and inorganic conditions of life” (Darwin, Origin of Species). All right, we have some data to look at. We can put a number to the frequency of beneficial mutations in a large sample. The number is zero.

Genome sequencing technology has progressed very rapidly in only the last few years. Nature just published results of the Exome Aggregation Consortium (ExAC), the largest survey of human genes to date. (An “exome” is the portion of the genome that codes for proteins.) The exomes from 60,706 individuals from a variety of ethnic groups have been collected and analyzed. If we multiply 60,000 people by the 20,000 genes in the human genome (the lowest estimate), we get a minimum of 1.2 billion genes that have been examined by ExAC for variants. That sounds like a pretty good sample size for scrutinizing some of those beneficial variations that Darwin said his law of natural selection could add up and preserve.

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human ‘knockout’ variants in protein-coding genes. [Emphasis added.]

Out of this high ratio of variants (one in eight bases shows variation, they said), there should be some proportion, even if small, that improves fitness. But we search the paper in vain for any mention of beneficial mutations. There’s plenty of talk about disease. The authors only mention “neutral” variants twice. But there are no mentions of beneficial mutations. You can’t find one instance of any of these words: benefit, beneficial, fitness, advantage (in terms of mutation), improvement, innovation, invention, or positive selection.

They mention all kinds of harmful effects from most variants: missense and nonsense variants, frameshift mutations, proteins that get truncated on translation, and a multitude of insertions and deletions. Quite a few are known to cause diseases. There are probably many more mutations that never survive to birth. As for natural selection, the authors do speak of “negative selection” and “purifying selection” weeding out the harmful mutations, but nowhere do they mention anything worthwhile that positive selection appears to be preserving.

Jay Shendure had participated in an earlier exome sequencing project on just 12 individuals. That was only seven years ago — an indication of the rapidity of progress in sequencing technology. In Nature, he shares his thoughts on the significance of ExAC, which is 5,000 times larger than his team’s effort was. He mentions “fitness.” Watch for it!

More than half of the approximately 7.5 million variants found by ExAC are seen only once. But collectively, they occur at a remarkably high density — at one out of every eight sites in the exome. For each gene, the authors contrasted the expected and observed numbers of variants that cause the production of truncated proteins, to search for regions containing lower-than-predicted levels of protein-truncating variants. This allowed them to identify several thousand genes that are highly sensitive to such variants — that is, unable to function normally after loss of one copy of the gene, even if the other copy is intact. Most of these genes have not yet been associated with disease, but mutation probably leads to embryonic death or strongly affects fitness in some other way. These genes are also intolerant of variants in regulatory DNA sequences that markedly alter levels of RNA synthesis from the gene, and are more likely than other genes to be implicated in genome-wide association studies of common disease.

Does he know of any variant that “strongly effects fitness in some other way” than embryonic death? If so, he would have listed it. Instead, all both papers talk about are disease, death, and intolerance to change. The amount of variability is indeed quite high, and the people who donated their genes to the project were alive in spite of their variants. But they sure don’t appear to be improving in any measurable way. Natural selection has plenty of bad variation to reject, but not much to add up and preserve.

Darwinians could argue that ExAC is not a large enough sample. We would need millions of exomes, or preferably whole genomes, to find the elusive beneficial mutations. That could be. As technology improves rapidly, perhaps we’ll find out before long. However, Doug Axe shows why this is unlikely.

Axe discusses sample sizes. His lab experience with protein folds leads him to the empirically supported conclusion that the sequence space for proteins (and the genes that encode them) is so fantastically large that blind search is hopelessly inadequate to find the good variants. And since natural selection cannot invent things, that’s all it has to work with. Remember, mutations are random. Finding good mutations is far less probable in a blind search than throwing a dart blindfolded from space and hitting a pre-specified target one millimeter in diameter. When the search space is “fantastically large,” adding more darts won’t help. You run into physical limits of time and energy cost.

For those who complain that Axe relies on intuition with his subtitle “How Biology Confirms Our Intuition That Life Is Designed,” rest assured that he does not (as he explains in a video here). The book is loaded with scientific evidence supporting design. He just shows that the “universal design intuition” common to humans from earliest childhood is scientifically correct in this case: when we see things that take knowledge to build, we know intuitively that someone had to have that knowledge. The news from ExAC provides additional empirical support for his contention that genes, proteins, and life are not fortuitous consequences of blind searches for good things. They look designed because they are designed.

Photo credit: © Sergey Nivens — stock.adobe.com.

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