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THE GENOTYPIC INTELLIGENCE OF EUROPEANS DECREASED SINCE BRONZE AGE (III)

Iunie 27, 2017
Between the 70 de novo mutations (DNM) 1.4% are in exome, 1% are nonsynonymous and 0.4% are synonymous. For 70 de novo SNP (and 5 de novo indels), an individual will have 75×1.4%=1.05 total de novo mutations in exome, 75×1%=0,75 de novo nonsynonymous mutations, and 0,30 de novo synonymous mutations.
The percentages of nonsynonymous, synonymous and total SNP in exome between total SNP in genome are around: 0.28%, 0,32% and 0,6% respectively (very slightly higher in non-Africans than in Africans), significantly lower than percentages of de novo mutations (1000 GENOMES, 2015). At an accumulation rate of 70 SNP per generation, the oldest SNP of human genome have at least 1.5 millions years.
It means 74% of de novo nonsynonymous mutations, 20% of de novo synonymous mutations and 47% of all de novo mutations in exome were eliminated each generation by natural selection. But it means that at least 47% of de novo mutations in exome (in one DNA base by two!) are deleterious enough to be eliminated by selection. At this strength of selection pressure on exome, only 53% of individuals in each generation could reproduce, and this individuals must have 4 surviving offspring to maintain the actual number of population. Clark & Hamilton (2006) found between 2.2 and 3.2 surviving children for all economic and social classes in pre-Industrial England, and this is far to strength of selection that operated during last 1.5 millions years.
Also, al least 8.2% of the human genome sequence is functionally significant and selectively constrained (Rands, 2014). Hence, each individual will have, on average, 8.2% x 75 =6.1 deleterious DNM.
According with The Omnigenic Theory of Boyle, Li & Pritchard (2017), it means that 35% of people could have one de novo mutation detrimental for intelligence in the exome, because 15,000 genes (75% of all genes) are expressed in the brain. Although, Spain (2015) found fewer rare SNP in exome of people with very high IQ. Also, the IQ of superpopulations in 1000 GENOMES parallel the proportion of individuals that carry uncommon minor SNP (MAF frequency lower than 5%) in genes (Rao, 2017). Furthermore, according to Omnigenic Theory, all humans have 6 IQ-decreasing DMN in non-coding genome. This signify that polygenic score on IQ/EDU must increase to maintain the genotypic IQ/EDU at the actual level, and even POLY IQ/EDU can increase and genotypic IQ/EDU can decrease, despite selection for high-IQ.
During 100 generations, the accumulation of the IQ-decreasing DMN in non-coding genome will be 600 SNP. If the average effect of an IQ-decreasing DMN equates the average effect of an IQ-increased SNP found by GWAS, the POLY IQ must increase with 600 SNP after 100 generations to maintain the actual level of genotypic IQ. If POLY IQ/EDU contains 30,000 SNP, this signifies a 2% increase of POLY IQ/EDU.
Woodley & Piffer (2017) found a 2% increase of POLY EDU during 114 generations, since Bronze Age.
REFERENCES

 

Boyle, E.A. et al (2017) An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell 169(7): 1177-1186 DOI: http://dx.doi.org/10.1016/j.cell.2017.05.038

Clark, G. & Hamilton, G. (2006) Survival of the Richest: The Malthusian Mechanism in Pre-Industrial England. The Journal of Economic History 66(3): 1-30

Rands, C.M. et al (2014) 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage. PLoS Genet 10(7): e1004525. doi:10.1371/journal.pgen.1004525

Rao, A.R. & Nelson, S.F. (2017) Calculating the statistical significance of rare variants causal for Mendelian and complex disorders. bioRxiv doi: http://dx.doi.org/10.1101/103218

Spain, S.L., Pedroso, I., Kadeva, N., Miller, M.B., Plomin, R. & Simpson, M.A. (2015). A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence. Molecular Psychiatry 21: 1145-1151.

Woodley, M.A. et al. (2017) Holocene selection for variants associated with cognitive ability: Comparing ancient and modern genomes. bioRxiv http://dx.doi.org/10.1101/109678

 

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