| In 1962, JV Neel put forth the'thrift genotype'hypothesis in his famous paper and refined it in later papers. This hypothesis suggests that genetic susceptibility to Diabetes mellitus is to some extent advantageous, and offers individuals with certain survival advantage. In the early years of life, the diabetic genotype was thrifty in the sense of being exceptionally efficient in utilization of food. It would thereby confer a survival advantage in the times of food shortages. However, in contemporary societies, food is usually available in unlimited amounts, the'thrift genotype'no longer provides a survival advantage, but renders its owners more susceptibility to obesity and diabetes.However, except for genes involved in energy metabolism, genes associated with regulation of water and salt can also be recognized as thrift gene under specific selection pressure. Based on genes in RAAS in water-electrolyte metabolism pathway, in this study we proposed that, "When humans lived in equatorial Africa, there were protogene in RAAS in order to adapt to the arid and hot environment condition. While after humans spread out of equatorial Africa, protogenes would lose their advantages in light of'thrift genotype'hypothesis. Humans with this kind of genes would become deleterious according to living disadvantage. Consequently, the mutation rate of related genes should present a striking geographical genetic distribution along humans'migratory route initialized from Africa. And there exists spatial dependence between the mutation rate of key genes in RAAS between populations and the gradient of global climate."Based on the above assumption, in the framework of spatial genetics,spatial statistics and spatial ecology, exploratory and confirmatory factor analysis were conducted to extract the latent global climate factors. On this basis, we further processd spatial autocorrelation analysis, Ordinary Kriging interpolation analysis, spatial overlay analysis, multiple linear regression analysis and geographically weighted regression analysis, in order to explore the new evolutionary evidence of'thrift genotype' hypothesis.Results:1. There are 2 latent factors extracted from the global climate variable, named as synthetic temperature factor and synthetic humidity factor respectively. The synthetic temperature factor dominates annual atmospheric temperature (standardized factor loading value 0.95), temperature climate (standardized factor loading value 0.96) and geography latitude (standardized factor loading value 0.94). The synthetic humidity factor dominates geography climatic zone (standardized factor loading value 0.83) and annual precipitation (standardized factor loading value 0.84).2.The result of spatial autocorrelation analysis indicates that the Moran's I of ACE D allele, AGT 235T allele, AT1R C allele, synthetic temperature factor and synthetic humidity factor were 0.61,0.33,0.59,0.57 and 0.7, respectively, all of them were statistically significant. The two synthetic climate factors and gene frequencies of key genes in RAAS all showed positive spatial correlation.3. ACE D allele, AGT 235T allele, AT1R C allele, synthetic temperature factor and synthetic humidity factor all revealed second trend order, after evaluating mean of prediction errors,root-mean-square of prediction errors, average standard error, standardized mean of prediction errors and standardized root-mean-square of prediction errors, we chose Spherical model as semi-variogram for ACE D allele, synthetic temperature factor and synthetic humidity factor and Gaussian model as semi-variogram for AGT 235T allele, AT1R C allele, respectively, in order to conduct the Ordinary Kriging interpolation method.4.The global regression model between synthetic climate factors(synthetic temperature factor and synthetic humidity factor) and mutation gene frequencies in RAAS indicated that the relationships between synthetic climate factors and ACE D allele, AGT 235T allele and AT1R C allele are statistically significant, furthermore, synthetic temperature factor affected the D allele positively while synthetic humidity factor negatively influenced the D allele, synthetic temperature factor and synthetic humidity factor had a positive influence on 235T allele and a negative effect on C allele.5. The local regression model between synthetic climate factors(synthetic temperature factor and synthetic humidity factor) and mutation gene frequencies in RAAS demonstrated the higher the temperature is, the bigger the coefficient of synthetic temperature factor is, which means, the higher the temperature is, the higher the D allele frequency is. On the other hand, the higher the humidity is, the smaller the coefficient of synthetic humidity factor is, which means, the higher the humidity is, the lower the D allele frequency is. Furthermore, this spatial dependence conforms to the route of out-of-africa migration.Conclusion:1. There are 2 latent factors extracted from the global climate variable. The synthetic temperature factor dominates annual atmospheric temperature, temperature climate and geography latitude, the higher the synthetic temperature factor, the higher the temperature. The synthetic humidity factor dominates geography climatic zone and annual precipitation, the higher the synthetic humidity factor, the higher the humidity. Via factor analysis, the multicollinearity problem is avoided.2. The genetic cline of D allele presents a striking geographical genetic distribution along humans'migratory route initialized from Africa.3. The spatial dependence between D allele and the synthetic climate factors reveals striking spatial structure and spatial heterogeneity, complies with humans'migratory route initialized from Africa. This indicates that the D allele is affect by the selection of climate.4. We have proved that the D allele is a'thrifty'genotype, providing new evolutionary ecology evidence for the'thrifty genotype'hypothesis.Innovations:1. We extend the concept of'thrifty genotype'hypothesis, regard the genes involved in water and salt metabolism as good candidates of'thrifty genotype", providing new vision to the proof of'thrifty genotype'hypothesis through non-energy metabolism approach.2. We employ new spatial genetics methods to identify the D allele as a'thrifty genotype', offering new evolutionary ecology evidence for the'thrift genotype' hypothesis.3. With the combination of spatial genetics, spatial statistics, spatial epidemiology, evolutionary ecology and climatology theories and methods, we offer new approaches to explore the'thrift genotype'hypothesis.Deficiencies: For ATIR and AGT gene, we fail to discover the evolutionary ecology evidence to prove them as'thrifty'genes, it may caused by the great error of Kriging interpolation generating from small and nonuniform distributed samples. Further work requires us to continue collecting data and optimizing the distribution pattern, in order to prove if these two genes are'thrift'genes. |
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