Via Pacific Standard.

Biology has provided us with a lot of "quality control machinery" in the cell, most of which is dedicated to making accurate copies of our DNA. Still, our genomes are remarkably unstable. Mistakes are made, and some of them are enormous. "Entire paragraphs and pages of our genetic text get duplicated or deleted. These large mutations are called “copy number variants” or CNVs, and they add or subtract copies of genes."

"Finding these mutations is only the beginning. Understanding why they cause particular effects is the next challenge."

The Giant Mutations in the Human Genome

By Michael White • October 10, 2014


(Photo: hakandogu/Shutterstock)

Our genomes are a mess—and we’re only beginning to understand the societal costs behind such genetic uncertainty.
•

Intellectual disability and developmental delay disorders are surprisingly common, but they’re frustratingly mysterious and hard to categorize. Patients often show a baffling mix of symptoms that are sometimes subtle and sometimes severe. Why are developmental disorders so confusing?

It turns out that there is a class of giant DNA mutations that share features of developmental disorders: They are surprisingly common, frustratingly diverse, and hard to categorize. Researchers are now discovering that these mutations play a big role in developmental delay disorders. The baffling symptoms are a consequence of the underlying genetic turmoil.

Despite the tremendous amount of quality control machinery in the cell devoted to making accurate copies of our DNA, our genomes are surprisingly unstable. Mistakes are made, and not just small typos: Entire paragraphs and pages of our genetic text get duplicated or deleted. These large mutations are called “copy number variants” or CNVs, and they add or subtract copies of genes.

Finding these mutations is only the beginning. Understanding why they cause particular effects is the next challenge.

Over the past decade, scientists have discovered CNVs to be shockingly common. One study found that we each carry, on average, about 1,000 CNVs, affecting roughly three percent of our genes. Different individuals have different CNVs, and so across the entire human population, much of the human genome is affected by these radical alterations.

It’s hard to know what impact all of this has on our health. We’re all walking around with these mutations, and most of us are just fine. In fact, many CNVs have existed in the human population for a long time and are broadly shared; many are relatively benign. But other CNV mutations are very rare, or even unique, and researchers are discovering that these giant mutations have a big medical impact. In fact, as one researcher recently put it, the ability to find CNV mutations was “the most substantial clinical benefit to come directly from the Human Genome Project in the first decade of the twenty-first century.”

Why? Because large DNA deletions or duplications explain many cases of developmental delay disorders. The most famous case is Down syndrome, which is caused by an entire extra chromosome. But there are many others disorders turn out to be due, in part, to CNVs, including autism spectrum disorders; more obscure ones like Angelman, DiGeorge, and Williams syndromes; as well as other uncategorized disorders. All together, intellectual disability and developmental delay affect about three percent of children. These disorders are costly to society and a huge challenge to the children and their families. Adding to the parents’ frustration is that they’re often unexplained: Doctors can’t always say what caused them, whether they’re likely to recur in siblings, or even how to treat them.

THAT IS NOW CHANGING. Researchers have begun to discover how these confusingly diverse, frustratingly subtle, and surprisingly common disorders are often caused by CNV mutations that are themselves confusingly diverse, frustratingly subtle in their effects, and surprisingly common in the population.

One team of researchers, led by Evan Eichler at the University of Washington, has been building a CNV “morbidity map” of developmental delay disorders. In a 2011 study, Eichler and his colleagues looked for rare, very large CNV mutations in nearly 16,000 children with developmental delay disorders and in 8,300 healthy subjects. While mutations certainly occurred in the healthy subjects—11 percent of them had relatively large mutations in their DNA—they were much more common in the children with developmental delay. The very largest mutations were almost 50 times more likely to occur in children with developmental delay than in the control subjects.

Finding these mutations is only the beginning. Understanding why they cause particular effects is the next challenge. Because these mutations are so varied, and because they often affect multiple genes at once, it can be hard to figure out exactly what went wrong. To get at this question, Eichler and his colleagues completed an even larger study that included nearly 30,000 children with developmental delay. With so many patients, the researchers were able to find patterns among the mutations and symptoms that at first seemed to have little to do with each other.

For example, the researchers found a group of patients whose various mutations had one thing in common: They damaged a gene called ZMYND11. Ordinarily, these patients wouldn’t be diagnosed with the same disorder: Some had severe intellectual disability, while others showed normal intelligence. But they all had some symptoms in common, including subtle facial deformities, delayed speech, and behavioral difficulties. The authors noted that one of the male patients had been very hard to categorize. He was diagnosed with “borderline personality disorder, bipolar disorder, psychosis, depression, low frustration tolerance leading to aggression and ADHD.” The genetic results show the underlying cause, and by relating his symptoms with other patients who carry ZMYBD11 mutations, they give his physicians a chance to find better ways to treat him.

As geneticists dig into the seismic disruptions caused by CNVs, the confusing landscape of developmental disorders will begin to make more sense. But as one researcher wrote in a comment on Eichler’s study, as we learn more about these common mutations, we’ll find that many people lie in a gray area. They’ll carry mutations “for which the majority of carriers do not meet the criteria for any medical diagnosis or disability,” but which clearly cause problems in some people. This will be a challenge to society: “On the one hand, huge numbers of people might be stigmatized.” But this might also allow us to help people: “On the other hand, these CNVs might be contributing substantially to societal disability and disparity, and affected individuals might be precisely the group that could benefit from early supportive intervention.” Of course, this problem isn’t unique to CNVs—it’s the ever-present dilemma we continue to face as we learn to better understand human genetics.


Michael White is a systems biologist at the Department of Genetics and the Center for Genome Sciences and Systems Biology at the Washington University School of Medicine in St. Louis, where he studies how DNA encodes information for gene regulation. He co-founded the online science pub The Finch and Pea. Follow him on Twitter @genologos.

More From Michael White

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• Sonic Hedgehog, DICER, and the Problem With Naming Genes
• Why Science Won't Defeat Ebola

More on Genes


The Social Life of Genes


We Now Can Edit Our Genes, but Should We? 

Humans Have Been Evolving Like Crazy Over the Past Few Thousand Years (Smithsonian 2012)

Evolution? Most Americans, in the neighborhood of 85%, do not believe in pure evolution (in the absence of a creator).

“Forty-six percent of Americans believe in the creationist view that God created humans in their present form at one time within the last 10,000 years. The prevalence of this creationist view of the origin of humans is essentially unchanged from 30 years ago, when Gallup first asked the question. About a third of Americans believe that humans evolved, but with God’s guidance; 15% say humans evolved, but that God had no part in the process.” (Gallop Poll, June 2012)

[Emphasis added to this quote.]

Despite this troubling ignorance, human beings have continued to evolve - even within the time-frame of Biblical history.

Humans Have Been Evolving Like Crazy Over the Past Few Thousand Years

November 29, 2012

A DNA molecule Photo: ynse / Wikimedia Commons

It’s a common argument of the know-it-all teen, fresh from an introductory biology course: “Life is so cushy now,” he might say, “People aren’t even evolving anymore.” As the argument goes, most people live a decently long life and have a chance to pass on their genes, since we aren’t so often being gobbled up by lions or succumbing to now-curable diseases. With this comes a dampening on the forces of natural selection, and a stagnation, or even weakening, of the human species.
But the truth, it seems, couldn’t be more different. Over the past 5 to 10 thousand years, says Nature, reporting on a new study, the genetic diversity in the human population has exploded, a bloom that serves as stage one in the process of evolution.

The human genome has been busy over the past 5,000 years. Human populations have grown exponentially, and new genetic mutations arise with each generation. Humans now have a vast abundance of rare genetic variants in the protein-encoding sections of the genome.

Brandon Keim, writing in Wired, says, “As a species, we are freshly bursting with the raw material of evolution.”

Most of the mutations that we found arose in the last 200 generations or so. There hasn’t been much time for random change or deterministic change through natural selection,” said geneticist Joshua Akey of the University of Washington, co-author of the Nov. 28 Nature study. “We have a repository of all this new variation for humanity to use as a substrate. In a way, we’re more evolvable now than at any time in our history.

Most of the new genetic shifts are extremely rare, appearing in only a small slice of the human population. The researchers look at their newly unveiled realization of the breadth of human diversity in terms of what it could mean for trying to understand the genetic basis of a number of diseases, or in what it tells us about humanity’s evolution history. But what it also means is that—come the emergence of a new disease or the turned tide of the zombie apocalypse—BAM, rapid evolution. Bring it, selection pressures. We got this.

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Here is the full text of the original article - it's mostly incomprehensible to a non-geneticist, or at least to me.

Analysis of 6,515 exomes reveals a recent origin of most human protein-coding variants

Wenqing Fu [1], Timothy D. O'Connor [1], Goo Jun [2], Hyun Min Kang [2], Goncalo Abecasis [2], Suzanne M. Leal [3], Stacey Gabriel [4], David Altshuler [4], Jay Shendure [1], Deborah A. Nickerson [1], Michael J. Bamshad [1,5], Population Genetics Working Group, Broad GO, Seattle GO, NHLBI Exome Sequencing Project, and Joshua M. Akey [1]

1. Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
2. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
4. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
5. Department of Pediatrics, University of Washington, Seattle, Washington, USA.

Copyright notice and Disclaimer
Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

Abstract

Establishing the age of each mutation segregating in contemporary human populations is important to fully understand our evolutionary history1,2 and will help facilitate the development of new approaches for disease gene discovery3. Large-scale surveys of human genetic variation have reported signatures of recent explosive population growth4-6, notable for an excess of rare genetic variants, qualitatively suggesting that many mutations arose recently. To more quantitatively assess the distribution of mutation ages, we resequenced 15,336 genes in 6,515 individuals of European (n=4,298) and African (n=2,217) American ancestry and inferred the age of 1,146,401 autosomal single nucleotide variants (SNVs). We estimate that ~73% of all protein-coding SNVs and ~86% of SNVs predicted to be deleterious arose in the past 5,000-10,000 years. The average age of deleterious SNVs varied significantly across molecular pathways, and disease genes contained a significantly higher proportion of recently arisen deleterious SNVs compared to other genes. Furthermore, European Americans had an excess of deleterious variants in essential and Mendelian disease genes compared to African Americans, consistent with weaker purifying selection due to the out-of-Africa dispersal. Our results better delimit the historical details of human protein-coding variation, illustrate the profound effect recent human history has had on the burden of deleterious SNVs segregating in contemporary populations, and provides important practical information that can be used to prioritize variants in disease gene discovery.


As part of the NHLBI sponsored Exome Sequencing Project (ESP), we sequenced the exomes of 6,515 individuals (Supplementary Table 1) including 4,298 European-Americans (EAs) and 2,217 African-Americans (AAs). Exome data were subjected to standard quality control filters as previously described6 (Supplementary Information), resulting in a data set of 1,146,401 autosomal protein-coding SNVs with a known ancestral state (709,816 and 643,128 in EAs and AAs, respectively) distributed across 15,336 protein-coding genes. To quantitatively estimate the age of each SNV (i.e., allele age), we developed a simulation approach to generate a series of coalescent trees for a specified demographic model, and estimated allele age based upon the derivation of Griffiths and Tavaré7 (Supplementary Information). We verified the accuracy and robustness of this approach to factors including recombination rate heterogeneity, population growth, migration, and purifying selection. Extensive coalescent simulations demonstrated that we could accurately estimate the expected allele age in the simulated data, although the variance associated with any individual SNV can be large (Supplementary Fig. 6 and 7).

We estimated the age of all 1,146,401 SNVs using six different previously inferred demographic models5,6,8-11, three of which considered recent explosive population growth5,6,8 (Supplementary Table 2). Estimates of allele age were generally robust across different demographic models, with the largest discrepancies resulting in a two-fold difference in average age across all SNVs (Supplementary Table 3 and Supplementary Fig. 8a). However, because most SNVs arose recently (see below), differences among demographic models were highly concordant (Supplementary Information). Accordingly, we report results based on a modified Out-of-African model9 in which accelerated population growth began 5,115 years ago with a per generation growth rate of 1.95% and 1.66% for EAs and AAs, respectively6.

The site frequency spectrum (SFS) of protein-coding SNVs revealed an enormous excess of rare variants (Fig. 1a). Indeed, we observed a SNV approximately once every 52 bp and 57 bp in EAs and AAs, respectively, whereas in a population without recent explosive growth we would expect the SNVs to occur once every 257 bp and 152 bp in EAs and AAs, respectively (Supplementary Information). Thus, the EA and AA samples contain a ~5 and ~3-fold increase in SNVs, respectively, attributable to explosive population growth, resulting in a large burden of rare SNVs predicted to have arisen very recently (Fig. 1b). For example, the expected age of derived singletons, which comprise 55.1% of all SNVs, is 1,244 and 2,107 years for the EA and AA samples, respectively. Overall, 73.2% of SNVs (81.4% and 58.7% in EAs and AAs, respectively) are predicted to have arisen in the past 5,000 years. SNVs that arose >50 thousand years (kyr) ago were observed more frequently in the AA samples (Fig. 1b), which likely reflects stronger genetic drift in EAs associated with the out of Africa dispersal.

The average age across all SNVs was 34.2±0.9 (s.d.) kyr in EAs and 47.6±1.5 kyr in AAs, and these estimates were robust to sequencing errors (Supplementary Information; Supplementary Fig. 9). As expected, SNVs shared between EAs and AAs were significantly older (104.4 kyr and 115.8 kyr for EAs and AAs, respectively) than population-specific variants (5.4 kyr and 15.3 kyr in EAs and AAs, respectively; Fig. 1c) (t-test; p<10-5 by permutation). Furthermore, there were large and significant differences among the average allele age of SNVs stratified by functional type (t-test; p<10-5 by permutation). For instance, splice site, nonsense, and non-synonymous SNVs were two to eight times younger compared to synonymous and noncoding variants (Fig. 1d). Moreover, we classified amino acids into four groups (non-polar and neutral, polar and neutral, acidic and polar, and basic and polar), and nonsynonymous SNVs resulting in changes between groups were significantly younger than those within groups (t-test; p<10-5 by permutation; Supplementary Fig. 10a). These differences in average allele age are likely due to varying intensities of selective constraint among different classes of SNVs12. Consistent with this prediction, we observed significantly higher values of the neutrality index, a measure of the direction and degree of departure from neutral evolution, in genomic regions enriched for younger variants (Spearman's correlation; p=0.004 and 0.001 for EAs and AAs, respectively; Supplementary Fig. 11), indicating a higher burden of deleterious SNVs.

To more directly identify putatively deleterious SNVs, we used four functional prediction methods (SIFT13, PolyPhen214, a likelihood ratio test15, MutationTaster16) applicable to nonsynonymous SNVs and two conservation-based methods (GERP++17 and PhyloP18) applicable to all SNVs (Supplementary Information). We found a strong inverse relationship between average SNV age and the number of methods that predicted a variant to be deleterious (Fig. 2a and 2b). Thus, SNVs predicted to be deleterious by multiple methods likely experience (on average) more intense purifying selection and may be of particular interest in disease mapping studies, or to weight differently in rare variant association tests. The age of nonsynonymous SNVs predicted to be deleterious by all six methods was 3.0 and 6.2 kyr in EAs and AAs, respectively, and 88.7% were <5 kyr (92.9% and 80.6% in EAs and AAs, respectively).

The strengths and weaknesses of functional prediction methods vary substantially and as a result the accuracy of any single method is modest15. Accordingly, we used a majority rule approach to identify a more conservative set of SNVs predicted to be deleterious6. Specifically, nonsynonymous SNVs predicted to be functionally significant by at least four methods and all other SNVs (synonymous, splice, and noncoding variants) predicted by two conservation-based methods were designated as deleterious. In total, 14.4% (164,688) of SNVs, including 152,633 nonsynonymous variants, met these criteria. We found that allele age was strongly related to the probability that a variant was predicted to be deleterious (Supplementary Fig. 12), with the fraction of SNVs predicted to be deleterious diminishing as allele age increased (Fig. 2c and Supplementary Fig. 13). The average age of conservatively defined deleterious variants was 5.2±0.3 kyr for EAs and 10.1±0.6 kyr for AAs. Moreover, 86.4% of these SNVs were predicted to have arisen in the past 5 kyr (91.2% and 77.0% for EAs and AAs, respectively), corresponding to the onset of accelerated population growth (Fig. 3a). In other demographic models, a similarly high proportion of deleterious SNVs were predicted to have arisen since the onset of accelerated growth rates, with the exact timing varying somewhat among models, but always in the timeframe of 5-10 kyr (Supplementary Table 3; Supplementary Fig. 8b and 8c).

Moreover, 7,197 (57.4%) of the 12,533 genes in EAs and 4,534 (37.5%) of the 11,607 genes in AAs that harbor one or more deleterious variants only possess deleterious SNVs with an estimated age of < 5 kyr (Fig. 3b). Thus, recent accelerated population growth has had a large influence on the number of genes harboring deleterious variants in contemporary populations. Notably, after correcting for exon length of each gene, three and eighteen genes in EAs and in AAs, respectively, have a significant excess of deleterious variants that arose after the onset of recent accelerated growth (p≤3×10-6; Supplementary Table 4), including 12 genes that have been associated with human diseases19 such as LAMC1 (premature ovarian failure20), LRP1 (Alzheimer Disease21), CPE (coronary artery atherosclerosis22), and KIAA0196 (hereditary spastic paraplegia23).

Next, we investigated the distribution of ages for conservatively defined deleterious SNVs in 849 genes that cause Mendelian disorders24, 2,663 genes associated with complex diseases19, 1,226 genes considered “essential” (i.e., a mouse knockout associated with lethality or sterility)25, and 11,711 genes classified as “other” (Supplementary Information). The proportion of deleterious SNVs in genes for Mendelian disorders (15.9%), essential genes (15.2%), and genes associated with complex diseases (15.1%) were each significantly higher (Fisher's exact test, p<10-16) compared to other genes (14.0%). In the EA samples, the proportion of deleterious SNVs did not decline monotonically as a function of age for Mendelian and essential genes. Rather, the proportion of deleterious variants with an estimated age of 50-100 kyr in Mendelian disease genes and 100-150 kyr in essential genes were elevated (Fig. 4a). This pattern was not observed in the AAs (Fig. 4a). To explore this observation, we performed simulations to estimate the probability that a deleterious SNV survives to the present day as a function of when the variant arose, the magnitude of selection, and presence or absence of an out of Africa bottleneck (Supplementary Information). Simulations of deleterious alleles in the presence of a bottleneck recapitulated the patterns observed in EAs (Supplementary Fig. 14). Specifically, in the presence of a bottleneck, weakly deleterious alleles (selection coefficient, s≤0.001) have an increased probability of survival precisely in the intervals 50-100 kyr and 100-150 kyr. Thus, our simulations suggest that genes underlying disease and essential genes are more functionally constrained relative to other genes, and the bottleneck associated with the out of Africa dispersal led to less efficient purging of weakly deleterious alleles26.

Finally, we found that the average age of deleterious variants (and the proportion of deleterious variants; Supplementary Fig. 15) was significantly different across 235 KEGG pathways (Kruskal-Wallis Rank Sum Test; p=2.5×10-3 and 1.08×10-6 for EAs and AAs, respectively; Fig. 4b; Supplementary Information). The average age across pathways did not vary significantly when all SNVs were considered (Kruskal-Wallis Rank Sum Test; p=0.259 and 0.075 for EAs and AAs, respectively), indicating the differences observed for deleterious variants likely represent heterogeneity of functional constraint across pathways. In general, the average age of deleterious variants in metabolic pathways was older than that in other pathways (Mann-Whitney test, p=1.11×10-4 and 6.27×10-9 for EAs and AAs, respectively), suggesting they are subject to less functional constraint. Conversely, deleterious variants in human disease pathways (Mann-Whitney test, p=0.03 for AAs) and in pathways involved in organismal systems were significantly younger (Mann-Whitney test, p=0.04 and 0.002 for EAs and AAs, respectively).

In summary, the spectrum of protein-coding variation is considerably different today compared to what existed even as recently as 200 – 400 generations ago. 86.4% of putatively deleterious protein-coding SNVs arose in the last 5-10 kyr, which are enriched for mutations of large effect (Supplementary Fig. 14), as selection has not had sufficient time to purge them from the population. It thus seems likely that rare variants play a significant role inheritable phenotypic variation, disease susceptibility, and adverse drug responses. In principle, our results provide a framework for developing new methods to prioritize potential disease causing variants in gene mapping studies. More generally, the recent dramatic increase in human population size, resulting in a deluge of rare functionally important variation, has important implications for understanding and predicting current and future patterns of human disease and evolution. For instance, the increased mutational capacity of recent human populations has led to a larger burden of Mendelian disorders, increased the allelic and genetic heterogeneity of traits, and may have created a new repository of recently arisen advantageous alleles that adaptive evolution will act upon in subsequent generations27.

Methods Summary

Exome sequences were obtained for 6,823 individuals, who were sequenced to high-coverage (median depth > 100x) on an Illumina GAII or HiSeq2000. Library construction, exome capture, sequencing, mapping, calling and filtering were performed as previously described, with minor modifications6 (and see Supplementary Information). After quality control and removal of related individuals, 6,515 individuals were retained. Ancestry of each individual was inferred by PCA performed on the sequence data. We developed a simulation approach based on coalescent theory to estimate allele age, which was applied to 1,146,401 autosomal SNVs with known ancestral states. A complete description of the materials and methods is provided in Supplementary Information.

Acknowledgements

We acknowledge the support of the National Heart, Lung, and Blood Institute (NHLBI) and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research; and the Population Genetics Project Team. We thank Jim Wilson and Ron Do for critical feedback on the manuscript. Funding for GO ESP was provided by NHLBI grants RC2 HL-103010 (HeartGO), RC2 HL-102923 (LungGO), and RC2 HL-102924 (WHISP). The exome sequencing was performed through NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO).
 

Footnotes

Author Contributions

WF and JMA conceived the analyses. DAN, SG, and DA oversaw data generation and QC. GJ, HMK, and GA developed algorithms and called SNVs. WF performed the majority of analyses with contributions from TDO. WF, MJB, JS, and JMA analyzed the data and wrote the manuscript with contributions from all authors.

Supplementary Information is linked to the online version of the paper at www.nature.com/nature.

References are available at the NIH site.

Are We Really Getting Dumber? Not Very Likely

In a recent pair of articles published in Trends in Genetics ("Our Fragile Intellect," Parts I and II), Gerald Crabtree has argued that we are not nearly as intelligent as we were 3000 years ago (he estimates that we all carry at least two gene mutations arising during that time that makes our intellect of emotions less stable).

Here is the offending quote

I would wager that if an average citizen from Athens of 1000 BC were to appear suddenly among us, he or she would be among the brightest and most intellectually alive of our colleagues and companions, with a good memory, a broad range of ideas, and a clear-sighted view of important issues. Furthermore, I would guess that he or she would be among the most emotionally stable of our friends and colleagues.

Here is more about his argument (The Register UK) - the papers are pay-walled.

"The larger the number of genes required" to carry out everyday tasks, Crabtree writes, "the more susceptible we are as a species to random genetic events that reduce our intellectual and emotional fitness."

Recent advances in genetic research, he says, have shown that "the number of genes required for normal human intelligence and abilities might be surprisingly large" – between 2,000 and 5,000 needed for full intellectual and emotional function.

Crabtree cites studies that have shown that genetic mutations are more common than previously thought, and that "a gene need not be human or brain specific in its function to be essential for our specific human intellectual abilities," due to the fact that genes function as links in a chain, and that "failure of any one of the links gives rise to deficiency."

Those deficiencies add up "Within 3000 years or about 120 generations," he says, "we have all very likely sustained two or more mutations harmful to our intellectual or emotional stability."

Crabtree disputes the idea that nature is a self-improving system. "One could argue that anything that occurs in Nature must be good for us," he says, "but this line of reasoning is quite incorrect."

So, if we're losing our intelligence, how did we get it in the first place? "Needless to say," he writes, "this is one of the most important questions of modern anthropology and the subject of much investigation and debate."

Although Crabtree freely admits that proposing answers to that question is "outside my comfort zone," he speculates that humans' expanding prefrontal cortex allowed the development of profound intellectual abilities earlier than is commonly thought.

"We seem to be forced to the conclusion that life as a hunter gather required at least as much abstract thought as operating successfully in our present society," he believes.

"Surprisingly," Crabtree writes, "it seems that if one is a good architect, mathematician or banker, these skills were an offshoot of the evolutionary perfection of skills leading to our ancestor's survival as nonverbal, dispersed hunter-gathers."

Well, then – if we humans were so smart back then, when did we start losing our intellectual and emotional abilities through gene mutation? According to Crabtree, the slide began when we began living in cities, and genetic selection began to focus more on such things as disease resistance rather than the improvement of abstract thought. As support for this argument, he cites the genetic principle that as an organism selects highly for one trait, other traits are selected against.

"It is also quite likely," he says, "that the need for intelligence was reduced as we began to live in supportive, high-density cities that made up for lapses of judgment or failure of comprehension."

In other words, our intellectual and emotional capabilities decayed because they weren't as important for survival.

As one might expect, not everyone (anyone?) agrees with Crabtree. Here are links (and a taste of) two different rebuttals.

From my perspective, anyone familiar with Ray Kurzweil's theory of exponential progress (law of accelerating returns) will understand that - daily - we process hundreds of times more information (at least) at an unconscious level (not even including the information and decisions we process at a conscious level) than an Athenian likely processed in a month (or more). As Kurzweil reminds us, "So we won’t experience 100 years of progress in the 21st century — it will be more like 20,000 years of progress (at today’s rate)."

Fragile intellect or fragile arguments?

Why Gerald Crabtree's speculations about declining human intelligence are wrong

• GrrlScientist and Bob O'Hara
• guardian.co.uk, Wednesday 14 November 2012

Life before Reality TV. Plato’s Academy mosaic from the Villa of T. Siminius Stephanus in Pompeii (1st century CE). Image: Public domain

It has often been observed that scientists, some rather brilliant, can get things hopelessly wrong when they stray outside their field. Examples are legion, and it has been dubbed the Linus Pauling effect:

The phenomenon is a familiar one: let's call it "the Linus Pauling effect." A highly respected and honored senior scientist, largely out of the mainstream and not up to date with the recent developments (and perhaps a bit senile), makes weird pronouncements about their pet ideas – and the press, so used to giving celebrities free air time for any junk they wish to say, prints and publishes it all as if it is the final truth.

Normally this happens when, say, a physicist starts thinking too hard about brains, but embarrassingly for me (one of my many sins is to be a geneticist), geneticists have a penchant for this too. What is really embarrassing is that more than one has made this mistake with a pet idea about genetics. I will now admit that I am going to step outside of my area of expertise (particularly with respect to human evolution and psychology), so if you are more knowledgeable in these areas, you can have some fun correcting my mistakes.

. . . . A couple hot-off-the-press articles published in Trends in Genetics have been garnering more attention than they're worth. In them, molecular geneticist Jerry Crabtree puts forward an argument that human cognitive abilities are declining:

I would wager that if an average citizen from Athens of 1000 BC were to appear suddenly among us, he or she would be among the brightest and most intellectually alive of our colleagues and companions, with a good memory, a broad range of ideas, and a clear-sighted view of important issues. Furthermore, I would guess that he or she would be among the most emotionally stable of our friends and colleagues. I would also make this wager for the ancient inhabitants of Africa, Asia, India, or the Americas, of perhaps 2000–6000 years ago.

. . . Crabtree fails to analyse the problem correctly.

. . . Crabtree argues that human intelligence has been declining, and remarkably, it has nothing to do with reality TV. Instead, his argument is that if we have lots of genes involved in intelligence, then it's fragile because if one gene "breaks" – mutates – everything goes awry and we become stupid. As the number of genes increases, it is more probable that one of those genes will mutate, and we know that each person carries roughly 60 new mutations in their genomes anyway. (Yup, it is generally accepted that we are all mutants. Collect your superpower on the way out.) 

Read the whole article.

* * * * *

We're Probably Not Getting Dumber

By Neuroskeptic

. . . . Crabtree's argument in a nutshell:

In Part I, he outlines the latest evidence showing that many thousands of genes contribute to human cognitive ability, and that because mutation rates are high (higher than previously believed), any given individual probably carries harmful variants of many of these genes. This is quite possibly true ,and interesting, but by itself it's nothing to do with declining IQ.

In Part II, Crabtree says that during human evolution, all of these genes were under strong selection pressure because any human or proto-human who wasn't smart enough to hunt, fight and survive in the stone age environment, would get eaten by a predator or starve. However, after these hunter-gatherer tribes became settled farming communities (in say 6000 BC), they were no longer so vulnerable, so the less intellectually able could live... and breed... leading to ever-more unintelligence genes.

Now, there's a lot of problems here. Many have said that this is all a bit like eugenics, and indeed it is, but that doesn't necessary mean it's wrong... no, it's wrong because the argument is flawed.

For instance, it's already been pointed out that, even if it recently got easier to stay alive, that doesn't mean it's got easier to get laid lots and have lots of kids; and sexual selection is a powerful force in evolution, perhaps even stronger than survival, and it probably favours higher intelligence.

However, there are other issues.

 Read the whole article.