Our Fragile Intellect

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"Our Fragile Intellect" is a 2012 article by American biochemist Gerald Crabtree, published in the journal Trends in Genetics . Crabtree's speculative and controversial thesis argues that human intelligence peaked sometime between 2,000 and 6,000 years ago and has been in steady decline since the advent of agriculture and increasing urbanization. Modern humans, according to Crabtree, have been losing their intellectual and emotional abilities due to accumulating gene mutations that are not being selected against as they once were in our hunter-gatherer past. [1] [2] This theory is sometimes referred to as the "Idiocracy hypothesis". [3]

Contents

Thesis

Crabtree argues that advancements in modern science allow new predictions to be made about both the past and the future of humanity and we can predict "that our intellectual and emotional abilities are genetically surprisingly fragile". [4] Recent studies of genes correlated with human intelligence on the X chromosome indicate typical intellectual and emotional activity depends on 10% of genes. Intelligence-dependent (ID) genes appear to be widely distributed throughout the entire genome, leading to a figure of 2,000 and 5,000 genes responsible for our cognitive abilities. Deleterious mutations in these genes can impact normal intellectual and emotional functioning in humans. It is thought that in just the last 120 generations (3000 years), humans have received two or more harmful mutations to these genes, or one every 20-50 generations. [4] [5] Crabtree points out that he loves our society's supportive institutions and wishes that they couldbe extended to include more of our population. The data that support the theory that our intellectual abilities are particularly susceptible to the accumulation of mutations begins with determinations of the human intergeneration mutation rate. This rate has been determined in several human populations to be about 1.20 x10-8 per position per haploid genome [6] [7] [8] [9] with an average father's age of 29.7 years. This rate doubles every 16.5 years with the father's age and ascribes most of the new mutations to the father during the production of sperm. [10] In contrast to popular opinion, this figure indicates that the biologic clock (in terms of accumulation of deleterious mutations with time) is ticking faster for men than for women. This figure of 1.20 x10-8 mutations per nucleotide per generation predicts that about 45 to 60 new mutations will appear in each generation. These mutations might accumulate or be removed by natural selection. The speculation that the nervous system and the brain would be more sensitive than other cell types and organs to the accumulation of these new mutations was based on the estimate of the fraction of genes necessary for normal development of the nervous system. The data quantifying the number of genes required for normal intellectual development comes from thousands of published studies (about 23,000 on PubMed from the National Library of Medicine) in which scientists have identified a mutated gene or a region of DNA associated with or causing human intellectual disability. These genes may not even be expressed in the brain. For example, the phenylalanine hydroxylase gene is expressed only in the liver, yet its mutation leads to severe intellectual disability due to the accumulation of metabolites . [11] [12] Many of these genes operate like links on a chain rather than a robust network underlining the fragility of our intellectual abilities. For example, mutations of a single nucleotide out of the 3 billion human nucleotides in our genomes in one copy of the ARID1B gene are a common cause intellectual disability. [13] Estimates of the total number of genes that when mutated give rise to intellectual disability is thought to be several thousand, perhaps 10-20% of all human genes, which produces a very large target for random mutations. In addition, neuronal genes tend to be large [14] [15] and hence increase the size of the genomic target region for random mutations. The simple combination of the number and size of genes required for normal brain development (>1000) and the fact that each new human generation has 45-60 new mutations per genome led Crabtree to suggest that our intellectual abilities are particularly genetically fragile over many generations. Seemingly the only practical implication of this theory is that perhaps men should have their children when they are young and that women should prefer younger men for mates.

Several counterarguments are presented. The Flynn effect, for example, shows an apparent increase in IQ around the world since 1930. Crabtree attributes the rise in IQ to advancements in environmental and public health measures as well as improved education and other factors. The Flynn effect also shows, argues Crabtree, not an increase in intelligence, but more intelligent test taking. [4] [16]

Reception

Kevin Mitchell, associate professor at the Smurfit Institute of Genetics at Trinity College Dublin agreed that genetic mutations could harm the development of the brain in humans and diminish intelligence; new mutations would become apparent in new generations. However, Mitchell criticizes Crabtree for failing to acknowledge the role of natural selection. According to Mitchell, natural selection "definitely has the ability to weed out new mutations that significantly impair intellectual ability". Mitchell describes Crabtree's argument as a conceptual fallacy and says Crabtree is "thinking about things in a wrong way". [2]

Biologist Steve Jones, Emeritus Professor of Genetics at University College London questioned the journal's decision to publish the paper, calling the study "a classic case of Arts Faculty science. Never mind the hypothesis, give me the data, and there aren't any". [17] Crabtree acknowledges that the data isn't there because a slow genetic deterioration in intelligence can't be detected by comparing it to people today. Instead, Crabtree argues that he is synthesizing already existing data and making a purely mathematical argument that estimates the probability of the number of new mutations that could result in cognitive deficits in future generations. [18]

Anthropologist Robin Dunbar at Oxford University argues against Crabtree's position that brain size was driven by tool use. Instead, Dunbar argues that the social environment drives intelligence. "In reality what has driven human and primate brain evolution is the complexity of our social world", says Dunbar. "That complex world is not going to go away. Doing things like deciding who to have as a mate or how best to rear your children will be with us forever." [19]

Cultural trope

Writer Andrew Brown notes that Crabtree's paper represents a familiar, reoccurring notion in both fiction and evolutionary biology. "The idea that civilized man is a degenerate and self-domesticated variation on the wild type is partly a cultural trope, a result of the anxieties of industrialized life", writes Brown. The idea, Brown observes, was popular in the early 20th century fiction of E. M. Forster ("The Machine Stops") and Jack London ( The Scarlet Plague ). It could also be found in the work of biologists such as Ronald Fisher, who espoused similar concepts in The Genetical Theory of Natural Selection (1930). The most important parts of Fisher's book, Brown writes, expounds on the theme that "civilization is dreadfully threatened by the way the lower classes outbreed the aristocracy." Brown finds related sentiments expressed in the work of W. D. Hamilton, who believed that the "life-saving efforts of modern medicine" threatened the human genome. [20]

See also

Related Research Articles

A microsatellite is a tract of repetitive DNA in which certain DNA motifs are repeated, typically 5–50 times. Microsatellites occur at thousands of locations within an organism's genome. They have a higher mutation rate than other areas of DNA leading to high genetic diversity. Microsatellites are often referred to as short tandem repeats (STRs) by forensic geneticists and in genetic genealogy, or as simple sequence repeats (SSRs) by plant geneticists.

<span class="mw-page-title-main">Fragile X syndrome</span> X-linked dominant genetic disorder

Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features may include a long and narrow face, large ears, flexible fingers, and large testicles. About a third of those affected have features of autism such as problems with social interactions and delayed speech. Hyperactivity is common, and seizures occur in about 10%. Males are usually more affected than females.

<span class="mw-page-title-main">FOXP2</span> Transcription factor gene of the forkhead box family

Forkhead box protein P2 (FOXP2) is a protein that, in humans, is encoded by the FOXP2 gene. FOXP2 is a member of the forkhead box family of transcription factors, proteins that regulate gene expression by binding to DNA. It is expressed in the brain, heart, lungs and digestive system.

Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

<span class="mw-page-title-main">Mutation rate</span> Rate at which mutations occur during some unit of time

In genetics, the mutation rate is the frequency of new mutations in a single gene, nucleotide sequence, or organism over time. Mutation rates are not constant and are not limited to a single type of mutation; there are many different types of mutations. Mutation rates are given for specific classes of mutations. Point mutations are a class of mutations which are changes to a single base. Missense and Nonsense mutations are two subtypes of point mutations. The rate of these types of substitutions can be further subdivided into a mutation spectrum which describes the influence of the genetic context on the mutation rate.

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<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and non-coding genes.

<span class="mw-page-title-main">Maziar Ashrafian Bonab</span>

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<span class="mw-page-title-main">Mutant</span> Phenotypically-different organism resulting from a mutation

In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It is a characteristic that would not be observed naturally in a specimen. The term mutant is also applied to a virus with an alteration in its nucleotide sequence whose genome is in the nuclear genome. The natural occurrence of genetic mutations is integral to the process of evolution. The study of mutants is an integral part of biology; by understanding the effect that a mutation in a gene has, it is possible to establish the normal function of that gene.

A nonsense suppressor is a factor which can inhibit the effect of the nonsense mutation. Nonsense suppressors can be generally divided into two classes: a) a mutated tRNA which can bind with a termination codon on mRNA; b) a mutation on ribosomes decreasing the effect of a termination codon. It is believed that nonsense suppressors keep a low concentration in the cell and do not disrupt normal translation most of the time. In addition, many genes do not have only one termination codon, and cells commonly use ochre codons as the termination signal, whose nonsense suppressors are usually inefficient.

<span class="mw-page-title-main">MT-ND6</span> Mitochondrial gene coding for a protein involved in the respiratory chain

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<span class="mw-page-title-main">AFF2</span> Protein-coding gene in humans

AF4/FMR2 family member 2 is a protein that in humans is encoded by the AFF2 gene. Mutations in AFF2 are implicated in cases of breast cancer.

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Neurogenetics studies the role of genetics in the development and function of the nervous system. It considers neural characteristics as phenotypes, and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same species, may not be identical. As the name implies, it draws aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code an organism carries affects its expressed traits. Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.

<span class="mw-page-title-main">Gene redundancy</span>

Gene redundancy is the existence of multiple genes in the genome of an organism that perform the same function. Gene redundancy can result from gene duplication. Such duplication events are responsible for many sets of paralogous genes. When an individual gene in such a set is disrupted by mutation or targeted knockout, there can be little effect on phenotype as a result of gene redundancy, whereas the effect is large for the knockout of a gene with only one copy. Gene knockout is a method utilized in some studies aiming to characterize the maintenance and fitness effects functional overlap.

<span class="mw-page-title-main">Genome evolution</span> Process by which a genome changes in structure or size over time

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Genome instability refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy.

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Gerald R. Crabtree is the David Korn Professor at Stanford University and an Investigator in the Howard Hughes Medical Institute. He is known for defining the Ca2+-calcineurin-NFAT signaling pathway, pioneering the development of synthetic ligands for regulation of biologic processes and discovering chromatin regulatory mechanisms involved in cancer and brain development. He is a founder of Ariad Pharmaceuticals, Amplyx Pharmaceuticals, Foghorn Therapeutics, and Shenandoah Therapeutics.

Human somatic variations are somatic mutations both at early stages of development and in adult cells. These variations can lead either to pathogenic phenotypes or not, even if their function in healthy conditions is not completely clear yet.

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Further reading