Paper short abstract:

To investigate how and why modern humans have adapted to endemic pathogens, we examined the polymorphism at primate DRB1, which encode a protein playing an important role in pathogen recognition. We found the presence of a human specific allele group that has been maintained in the population before the divergence from chimpanzees.

Paper long abstract:

Modern humans live in a wide variety of environments, from polar to tropical regions. The endemic pathogens in these areas differ, and humans are possible to be infected by these pathogens. Modern humans disseminated across the world from Africa 100,000 to 50,000 years ago and have adapted to regions with various endogenous pathogens. On the other hand, chimpanzees have remained in Africa since their divergence from humans approximately 6 million years ago. This begs a question of how modern humans acquired resistance to a variety of pathogens in different environments. In the present study, we examined phylogenetic relationships among primate alleles of the major histocompatibility complex (MHC) DRB1 gene, which is an important genetic system for protection against infectious disease. The analysis identified two major groups of HLA-DRB1 alleles, Groups A and B, and demonstrated that Group A was a human-specific. Our estimates of divergence time of these alleles suggested that HLA Group A alleles have been maintained in the human population before the divergence of humans and chimpanzees. On the other hand, most orthologs of HLA Group A alleles have been lost in the chimpanzee probably due to changes in selective pressures. Three HLA Group A alleles have likely increased in frequency among human populations after their out-of-Africa event, suggesting that these HLA molecules contribute to the local adaptation of humans.

Paper short abstract:

Human cold adaptation was important for survive during ice age. mtDNA haplogroup is suggested to relate cold adaptation. We try to discuss the relationship between modern human cold adaptability and mtDNA haplogroup.

Paper long abstract:

Human cold adaptability is affected by various factors; seasonal change, lifestyle, and genetic factor. However, genetic factor is still unclear. mtDNA haplogroup which determined by mtDNA polymorphism is one of genetic factor. Since mitochondria functions closely relate to human thermogenesis involving shivering thermogenesis (ST) and non-shivering thermogenesis (NST) to maintain body temperature, some previous studies suggested that mtDNA polymorphism shaped by cold climate and some polymorphism relate to human cold adaptation. We already reported haplogroup D had higher body temperature during severe cold (10 C°) in summer, but no difference in winter. The purpose of present study was to the interaction between mtDNA haplogroup and seasonal variation that contributes to cold adaptability under mild cold, focusing on NST and haplogroup D in Japanese. Seventeen university students (eight haplotype D participants and nine haplotype non-D participants) participated in the present study in the summer and winter. The climate chamber used was programmed so that ambient temperature dropped from 28 °C to 16°C over the course of an 80 min period. Oxygen intake, rectal temperature, skin temperature of participants was recorded during experiments. Results show that, in summer, there was no significant difference between D and non-D group. In winter, the increase in energy expenditure calculated by oxygen intake was higher in the haplogroup D than in the haplogroup non-D group. Because shivering was not occurred during experiment, this increase of energy expenditure was considered to be NST. Thus, present study suggests that mitochondrial haplogroup affects cold adaptability, and haplogroup D have higher NST in winter.

Paper short abstract:

Humans show various responses to the environmental stimulus, “physiological polytypisms.” In this study, we examined an association between the physiological polytypism of response to light stimulus and genetic polymorphism(s), and found that the ratios of melatonin suppression were evidently related to the PER2 haplotypes.

Paper long abstract:

Various responses to the environmental stimulus in the individual level of humans are called “physiological polytypisms.” However, it has been unclear if these are regulated by genetic variations. In this study, we measured ratios of melatonin suppression of 43 Japanese subjects under light-stimulus in constant darkness, and genotyped 6 SNPs in the PER2 gene, which is one of important clock genes related to human circadian rhythm, for the subjects and 145 non-subject Japanese.

Three common haplotypes accounted for more than 95 % of the subjects, and one of the haplotypes had a significantly low sensitive response to light-stimulus (p < 0.01) than the others. The homozygote of the low-sensitive haplotype showed significantly lower rates of melatonin suppression (p < 0.05), and the heterozygotes of the haplotypes varied their ratios. Comparing with the global haplotype frequencies, the low-sensitive haplotype was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree.

These results suggest that (1) the physiological polytypisms for light-stimulus is evidently related to the PER2 polymorphisms, and that (2) the haplotype with low-sensitive response is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types, suggesting that the high-sensitive haplotypes have spread to the world after out-of-Africa migration of modern humans.

Paper short abstract:

Human sleep and circadian rhythm adapt to a 24-hour light/dark cycle. The melanopsin photoreceptor in the retina plays an important role in circadian photoentrainment. We found that melanopsin gene polymorphism is associated with sleep/wake timing.

Paper long abstract:

The human sleep/wake cycle is adjusted by circadian rhythms that adapt to a 24-hour light/dark cycle. The melanopsin photoreceptor in the retina plays an important role in circadian photoentrainment in the natural environment. However, artificial light at night has adverse effects on human sleep and circadian rhythm in modern society. We have already found that melanopsin gene polymorphism is associated with pupillary light response, but the association with sleep/wake timing has remained unclear. A total of 348 healthy Japanese university students participated in this study. The genotypes of rs1079610 (I394T) located in the coding region were analyzed. Bedtime, wake time and midpoint of sleep on weekdays of CC subjects were significantly later than those of TT and TC subjects. We have already found that pupilloconstriction in subjects with the C allele is highly responsive to light. The delayed sleep/wake timing of CC subjects might be a consequence of the high responsiveness to light at night since exposure to light at night induces phase delay. C allele frequency of I394T in the European population is larger than that in the Asian-Japanese and Sub-saharan African populations. High responsiveness to light may be an adaptive trait for a short photoperiod in European people living in high latitude areas. However, our results suggest that high responsiveness to light is a cause of delayed sleep timing in adolescents living under artificial light at night in modern society.