Ruiz-Narváez E
Department of Nutrition, Room 202, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA.
J Med Genet. 2005 Jul;42(7):547-50. doi: 10.1136/jmg.2004.026765.
The thrifty genotype hypothesis proposes that genetic susceptibility to type 2 diabetes results from the positive selection of "thrifty" alleles in the past. A corollary of this hypothesis is that genetic variants protecting against the development of diabetes are "unthrifty" and thus subject to negative selection during human evolution.
It was assessed whether age estimates of the diabetes protective PPARG Ala12 allele indicate effects of natural selection. Based on published data from four populations, the date of origin of the diabetes protective PPARG Ala12 variant was estimated using both allele frequency and linkage disequilibrium (LD) with the C1431T single nucleotide polymorphism in exon 6 of the PPARG gene.
The best LD based estimate of the age of the Ala12 allele gave an average of approximately 32,000 years with a maximum upper bound of approximately 58,000 years. Assuming a population with a growth rate of r = 0.01 per generation, the frequency based estimate of the age of the Ala12 variant gave an average of approximately 27,000 years with a maximum upper bound of approximately 42,000 years.
The similarity of both time estimates is consistent with selective equivalence of the diabetes protective PPARG Ala12 allele and the diabetes susceptible PPARG Pro12 allele.
节俭基因型假说提出，2型糖尿病的遗传易感性源于过去对“节俭”等位基因的正向选择。该假说的一个推论是，预防糖尿病发生的基因变异是“不节俭的”，因此在人类进化过程中会受到负向选择。
评估了糖尿病保护性PPARG Ala12等位基因的年龄估计是否表明自然选择的作用。基于来自四个人群的已发表数据，使用等位基因频率以及与PPARG基因第6外显子中C1431T单核苷酸多态性的连锁不平衡（LD）来估计糖尿病保护性PPARG Ala12变异的起源日期。
基于LD对Ala12等位基因年龄的最佳估计平均约为32000年，最大上限约为58000年。假设一个种群的世代增长率r = 0.01，基于频率对Ala12变异年龄的估计平均约为27000年，最大上限约为42000年。
两种时间估计的相似性与糖尿病保护性PPARG Ala12等位基因和糖尿病易感性PPARG Pro12等位基因的选择等效性一致。
