The deleterious mutation load is insensitive to recent population history
Yuval B Simons et al.
Nature genetics 2014 Feb
We use population genetic models to show that recent human demography has likely had little impact on the average burden of deleterious mutations.
This prediction is supported by two exome sequence datasets showing that individuals of west African and European ancestry carry very similar burdens of damaging mutations.
Given these observations, it is natural to ask whether recent demographic history has impacted the burden of genetic disease in modern human populations3, 6, 11,12.
Keinan and Clark3 recently hypothesized that “Some degree of genetic risk for complex disease may be due to this recent rapid increase in the number of rare variants in the human population”.
We studied three types of demographic models thought to be relevant for human populations:
(i) a bottleneck;
(ii) exponential growth starting from a constant-sized population;
(iii) a complex demographic model for African Americans (including rapid recent growth) and European Americans (including two bottlenecks followed by growth) inferred by Tennessen et al.5.
Figure 1 illustrates the impact of a bottleneck and population growth on the numbers of deleterious variants with strong selection (s=1%).
Each data line shows the expected number of variants, or alleles per MB, assuming semi-dominant mutations (C and D) or recessive mutations (E and F) with s = 1% and mutation rate per site per generation=10−8. Versions of these plots with linear scales can be found in Supplementary Figures 13, 14, and 16.
The plot shows mean frequencies in each population, plus and minus two standard errors, using exome sequence data from Fu et al.6. Here a site is considered an SNV if it is segregating in the combined AA-EA sample of 6515 individuals. The functional classifications of sites are from PolyPhen222 with bias-correcting modifications. The AA and EA mean frequencies are essentially identical within all five functional categories (p>0.05).
Yuval B Simons et al.
Nature genetics 2014 Feb
この論文によれば、過去においてボトルネック効果を経ていないアフリカ系アメリカ人とボトルネック効果を経ているヨーロッパ系アメリカ人との比較から、両者で集団内から削除されるべき遺伝子比率は異ならず、事実上はボトルネック効果は、害悪遺伝子頻度変化にはあまり影響しないという重要な仮説を提示したものと言える。
朝鮮人は私の推定が正しいのであれば、13世紀のモンゴル侵攻と一時的な寒冷化により、1230～1259年頃において人口が約85％程度減少したと思われる。これをボトルネック効果と呼びうるのかどうかは、減少後の人口も約20万～30万程度（＝遺伝的多様性が100％確実に保ちうる人口サイズ）あることから疑問であるものの、非同義変異比率が他の集団よりも高いという致命的な欠陥を有する奇妙な民族集団が形成された主原因であると推察される。しかし、理論上、人口の大幅な減少→非同義変異比率の上昇は、直ちにはつながらない。今後の課題である。
昨日、韓国では大統領が弾劾され大統領職を外れたが、同時に尹氏は内乱罪でも別途刑事告発されており今後は全軍の司令官であった尹氏の内乱罪刑事裁判が行われる。一体全体、馬鹿げた法律論は別として、全軍の最高司令官に内乱罪に問うことなどバカの極致であり、朝鮮人の精神面での遺伝的な異常性を象徴しているともいえる
朝鮮人は私の推定が正しいのであれば、13世紀のモンゴル侵攻と一時的な寒冷化により、1230～1259年頃において人口が約85％程度減少したと思われる。これをボトルネック効果と呼びうるのかどうかは、減少後の人口も約20万～30万程度（＝遺伝的多様性が100％確実に保ちうる人口サイズ）あることから疑問であるものの、非同義変異比率が他の集団よりも高いという致命的な欠陥を有する奇妙な民族集団が形成された主原因であると推察される。しかし、理論上、人口の大幅な減少→非同義変異比率の上昇は、直ちにはつながらない。今後の課題である。
昨日、韓国では大統領が弾劾され大統領職を外れたが、同時に尹氏は内乱罪でも別途刑事告発されており今後は全軍の司令官であった尹氏の内乱罪刑事裁判が行われる。一体全体、馬鹿げた法律論は別として、全軍の最高司令官に内乱罪に問うことなどバカの極致であり、朝鮮人の精神面での遺伝的な異常性を象徴しているともいえる
Abstract
We use population genetic models to show that recent human demography has likely had little impact on the average burden of deleterious mutations.
This prediction is supported by two exome sequence datasets showing that individuals of west African and European ancestry carry very similar burdens of damaging mutations.
Given these observations, it is natural to ask whether recent demographic history has impacted the burden of genetic disease in modern human populations3, 6, 11,12.
Keinan and Clark3 recently hypothesized that “Some degree of genetic risk for complex disease may be due to this recent rapid increase in the number of rare variants in the human population”.
Results
We studied three types of demographic models thought to be relevant for human populations:
(i) a bottleneck;
(ii) exponential growth starting from a constant-sized population;
(iii) a complex demographic model for African Americans (including rapid recent growth) and European Americans (including two bottlenecks followed by growth) inferred by Tennessen et al.5.
Figure 1 illustrates the impact of a bottleneck and population growth on the numbers of deleterious variants with strong selection (s=1%).
Figure 1. Time course of load and other key aspects of variation through a bottleneck (A) and exponential growth (B).
Each data line shows the expected number of variants, or alleles per MB, assuming semi-dominant mutations (C and D) or recessive mutations (E and F) with s = 1% and mutation rate per site per generation=10−8. Versions of these plots with linear scales can be found in Supplementary Figures 13, 14, and 16.
Figure 3. Observed mean allele frequencies in African and European Americans at various classes of SNVs.
The plot shows mean frequencies in each population, plus and minus two standard errors, using exome sequence data from Fu et al.6. Here a site is considered an SNV if it is segregating in the combined AA-EA sample of 6515 individuals. The functional classifications of sites are from PolyPhen222 with bias-correcting modifications. The AA and EA mean frequencies are essentially identical within all five functional categories (p>0.05).
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