The 42nd Annual Meeting of the Japanese Environmental Mutagen Society (JEMS42) was held on November 29 and 30, 2013, at the Okayama Convention Center in Okayama. The venue is two minutes walk from the Okayama Station. The main theme of JEMS42 was “Mutation and evolution: where do we come from and where are we going?” The number of attendants was approximately 300. One day before the meeting, the Editorial Board Meeting, the Administrative Board Meeting, the Council Meeting, and three subgroup meetings were held at Shujitsu University. The subgroups were the Mammalian Mutagenicity Study Group (MMS), the Bacterial Mutagenicity Study Group (BMS), and the Environmental Epigenomics Study Group (EGG).
Bipedalism paved the way to delivery of immature babies and development of the brain after birth. This communication presents the argument that hairlessness allowed hominins to access fire through wildfires, which occurred frequently after a climate shift from a wet to a dry environment 2.5 million years ago (Ma). Initially, naked hominins approached fire for warming, but soon must have come across burnt animals in the aftermath of wildfires. They learned the taste of burnt meat, which must have been a driving force compelling them to become meat-eaters. Hominins must have learned gradually how to control fire and how to repel hairy animals that abhor fire. Because they could neither run fast nor have muscles sufficiently strong to compete with large carnivores' fangs and claws, they chose not to be hunters but robbers. When they found that a carnivore had killed a prey animal, they approached the hungry predator and repulsed it using fire and stones, then claiming the prey intact. This is the core of the human robber hypothesis. The timing of global cooling, the appearance of savannahs, the appearance of transitional humans, decline of large predators, the manufacture of stone tools, and the start of cooking largely coincide at 2.5 Ma. They also smoked out animals from their dens or caves, and robbed them of shelter and territory. Cooked meat is both tasty and easily digested, providing hominins with rich nutrients sufficient to enlarge the brain, while most large carnivores were forced to extinction. Consequently, the use of fire, facilitated by hairlessness, must have played important roles in protecting hominins from cold, in repelling predators, in robbing large carnivores of prey and dwellings, and in providing the brain with nutrients for strong growth into adolescence. Development of the eccrine glands is also discussed as a result of hairlessness.
Three characteristics, i.e., bipedalism, nakedness, and the family reproductive unit, distinguish humans from other primates. Once a hairless mutation was initially introduced, these three could be explained inseparately. All primates except humans can carry their babies without using their hands. A hairless mother would be forced to stand and walk upright to hold a baby. As her activities were markedly limited, the male partner had to collect food and carry it to her to keep their baby from starving. He must have been sexually accepted by her at any time as a reward for food. Sexual relations irrespective of estrus cycles might have strengthened the pair bond, leading to family formation. Savannahs appeared 2.5 million years ago (Ma), which forced hominins to terrestrial life, but the ground was full of danger and a larger brain became advantageous. Wildfires occurred frequently; naked hominins approached fire for warming, but soon must find burnt animals in the aftermath of wildfires. The taste of burnt meat must be a driving force for hominins to become meat-eaters. They must have learned how to control fire and how to repel hairy animals that hate fire. To compete with large carnivores with fangs and claws, they became not hunters but robbers. When robber hominins found that a carnivore had killed a prey animal, they approached the predator and repelled it away from the victim using fire, then claiming the prey intact. Major events such as the timing of global cooling, the appearance of savannahs, the appearance of early humans, decline of large predators, the manufacture of stone tools, and the start of cooking largely coincide at 2.5 Ma. Cooked meat must be tasty and easily digested, providing hominins with nutrients sufficient to enlarge the brain, while most large carnivores were forced to extinction. Thus, hairlessness created humans.
There are more than 300 species of primates, including human beings, on earth. Human beings share various characteristics such as morphology, physiology, ethology, and sociology with other primates. Primates have a common ancestor, and so a common evolutionary history. Various social units formed in primate societies exhibit a range of behaviors including monogamy, polygyny, polyandry, and multi-male/multi-female relations. Among all primates, however, only humans have a social “family” unit. The family is defined as a small-scale kin group consisting of a husband, a wife, and a child. This is the smallest social unit in human society, and it is found in almost all human societies. How would this social unit, unique to humans, have been formed? Johanson and White (1976) discovered the fossilized remains of Australopithecus afarensis, the Hominidae, who lived 3.75 million years ago, in Hadar, Ethiopia. These fossils were found to be a lineal ancestor to the human race, and were named the “first family,” because the fossils of 13 individuals (both sexes, including children) were excavated from the same ruins. However, the first family's behaviors and societies were not fossilized. Development of the family unit was a dynamic process, and therefore it is only speculation that human evolution resulted from a group of close relatives who had in turn evolved from a common ancestor. Imanishi (1951) identified four conditions necessary to a human family as being: 1. a taboo against incest, 2. exogamy, 3. community, and 4. the division of labor. I would like to discuss the origins of human society by comparing our closest relatives, the society of apes, to the four conditions Imanishi described as necessary to a human family.
Approximately 200,000 years ago, early modern humans (Homo sapiens) appeared somewhere in Africa, and approximately 60,000 years ago, a few members of the early modern humans migrated from Africa to the rest of the world. Finally approximately 10,000 years ago, they were distributed almost all land surfaces of the globe. In the course of expansion, modern humans drove off pre-modern Homo that existed in various regions. However, recent genomic analysis of the nuclear DNA extracted from pre-modern Homo fossils revealed that some pre-modern Homo interbred with some modern humans and left their genes in our genomes.
People often would like to think themselves as special existence. In studies on organismal evolution, unexpectedly many researchers believe in contribution of positive selection for evolution of characters which made us human. However, most of evolution at genomic level is neutral process, and this is also true for evolution at protein level. There is no exception in evolution toward human lineage. I would like to show various examples on this point, including studies of my group, and would like to confirm natural phenomenon that most of evolution which produced Homo sapiens was neutral. It should also be noted that majority of this paper is from “Introduction to Evolutionary Genomics” written by Saitou (Saitou N. Berlin: Springer; 2014).
Epidemiological studies suggest UVA play a significant role in the induction of skin cancers. Nucleic acids and proteins have extremely weak extinctions in UVA and visible light regions. The absorption of UVA energy is dependent on endogenous or exogenous sensitizers, and the photogenotoxicity of UVA is derived from the excited sensitizers. Photosensitive medicines, carcinogens and endogenous compounds can participate in UVA-induced photogenotoxicity and photomutagenicity. Irradiated medicines reported to be involved in photosensitization and phototoxicity such as antipsychotics, antihistamine agents, non-steroidal anti-inflammatory drugs, antihypertensive drugs, anti-diabetic agents, antibiotics, antifungal drugs and antibacterial agents. As an alternate pathway for activation, several carcinogens can be converted with UVA to reactive intermediates that bind DNA in the absence of the activation enzymes. Several endogenous compounds have also been reported to act photosensitizers. Photogenotoxicity and photomutagenicity are unwanted side-effects related to the UV-mediated activation of chemicals. In considering risks and benefits, the interrelationship between light, chemicals and human health remain an important topic of research.
Photogenotoxicity is generally defined as the ability of chemicals to induce genotoxic effects under ultraviolet (UV) and/or visible light. The potential of chemically-induced epigenetic alterations in the nucleus to affect the genotoxicity of UV has been discussed in this review. UV induces the formation of pyrimidine dimers and is, therefore, considered to be genotoxic. Pyrimidine dimers are effectively repaired by nucleotide excision repair (NER), a process in which the relaxation of nucleosome interactions is considered necessary. Histone modifications such as acetylation are a cause of the change of nucleosome interactions, and previous studies and reviews demonstrated that these modifications altered the generation as well as repair of DNA damage. We previously reported that the hyperacetylation of histones enhanced sensitivity to UV light and suppressed NER. Some chemicals, metals, pesticides, and hormones have been shown to acetylate histone residues. The dysregulation of histone modifications caused by these chemicals may affect the formation of pyrimidine dimers following exposure to UV light as well as repair ability, which suggests the new concept of “photogenotoxicity”.
To reveal the contamination levels of ambient air with particulate matter and mutagens in Japan and the influence of their long-range transport from the Asian continent, we collected airborne particles at 10 sites, from rural sites to metropolitan areas, in central and western areas of Japan for a year, from July 2008 to June 2009. The fluctuation patterns and levels of airborne particle concentration were similar among the 10 sites, and remarkable increases of the concentrations were seen on a few sampling dates, including March 16 and 17, 2009. Most airborne particles collected at the 10 sites showed mutagenicity toward Salmonella typhimurium YG1024 without a mammalian metabolic system (S9 mix) in the Ames test. The mutagenicity levels were quite different among the sampling sites, and the levels seemed to be dependent on the extent of urbanization and industrialization of the subject areas. At Yurihama, a rural site on the west coast of Japan, the mutagenicity level of airborne particles was low, but the particles collected on March 16 and 17, 2009, showed relatively high mutagenicity, >40 revertants/m3, in YG1024 without S9 mix. Airborne particles collected on March 16 and 17, 2009, at most sites showed relatively high or high mutagenicity, >80 revertants/m3, in YG1024 without S9 mix. High coefficients of correlation were found between the concentration and mutagenicity of airborne particles collected in spring, from March to May, for many sites. The results of back trajectory analysis indicated that air masses for March 16 and 17, 2009, had moved from the Asian continent to Japan. The arrival of Asian dust in central and western areas of Japan on those days was reported by the Japan Meteorological Agency. These results suggest that the arrival of mutagens accompanied by Asian dust could be evidently found at Yurihama on March 2009.
Asian dust storm (ADS) contains airborne particles that can have negative effects on health in Asian countries. The objective of the study was to investigate the association of ADSs with asthma and airway inflammation in western Japan. We designed a telephone survey to assess the influence of an ADS on upper and lower respiratory systems in adult patients with asthma. The patients also recorded scores for daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF). Production of interleukin-8 was assessed in THP-1-derived IL-8 reporter cell line (THP-G8) cells that were exposed to airborne particles collected during ADS days. Our results showed that 11–22% of patients with asthma had worsening of lower respiratory tract symptoms on ADS days. The ADS also had a significant negative association with pulmonary function of patients with asthma. However, emergency treatment for augmented symptoms caused by the ADS was not needed because exacerbation of asthma was mild in adult patients. Comorbid allergic rhinitis has been suggested to be an important determinant of worsening of lower respiratory symptoms during an ADS in patients with asthma. Airborne particles collected on ADS days induced interleukin-8 in THP-G8 cells, but this effect was not observed for the original soil sample of the ADS. Thus, exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma and ADS airborne particles may increase airway inflammation through elevation of interleukin-8.
Relocation of bacteria over long distances is a key issue in global bacterial inoculation. Certain of mobile bacteria then can adapt to their new location and affect the established ecosystem. Aeolian dust particles are thought to be carriers of microbes but definitive research is lacking. The contribution of aeolian dust to global migration of bacterial cells and their genes was therefore examined by culture-independent approaches. Asian dust particles were collected over the Japan Sea (10 km from coasts) at an altitude of 900 m to avoid contamination of soil particles lifted from ground, on 12 November 2010 (midst of the event, visibility: less than 10 km), 13 Nov. 2010, 16 Nov. 2010 (end of the event, visibility: 25 km) and 2 May 2011 (midst of the event, visibility: less than 10 km), with a sampler set in a small airplane. Microbial cells on dust particles were directly visualized by bio-imaging with laser scanning microscopy equipped with a microspectrophotometer, based on their specific fluorescence. 16S rRNA gene was directly extracted and it was then confirmed by quantitative PCR that bacterial abundance on collected dust particles drastically declined from 105 cells/m3 to less than 1/100 as the dust event subsided. Taxonomically diverse bacteria were found by sequencing of 16S rRNA genes of clones obtained from each collected Asian dust sample, such as Actinobacteria, Bacilli and Sphingobacteria. Some of these bacteria retained growth potential despite the long-range transportation. These results demonstrate that bacteria attach to aeolian dust particles and migrate globally during dust events thus may contribute to the diversity of the bacterial gene pool.
Airborne particulates have been continuously collected at four cities in Japan starting in the late 1990s, at major cities in China, Korea and Russia starting in 2001 and at Noto peninsula starting in 2004. After extracting and cleaning up particulates, nine polycyclic aromatic hydrocarbons (PAHs) and eleven nitropolycyclic aromatic hydrocarbons (NPAHs) were determined by HPLC with fluorescence and chemiluminescence detections, respectively. Annual concentrations of PAHs and NPAHs at the cities were in the order, China>Russia>Korea>Japan. Concentrations of PAHs and NPAHs in Japanese cities significantly decreased but different tendencies were observed in Chinese and Russian cities. On the Noto peninsula, which is in the main path of winter northwest winds and a year-round jet stream that blow from the Asian continent to Japan, the concentrations of PAHs and NPAHs were high in winter and low in summer every year. A cluster analysis and back trajectory analysis indicated that PAHs and NPAHs at the Noto peninsula in winter mainly came from coal burning systems in Northeast China.
Lung adenocarcinoma (LADC) is the most common histological type of lung cancer and its incidence is increasing worldwide. Genetic polymorphisms, including single nucleotide polymorphisms (SNPs), underlie inter-individual differences in cancer susceptibility, and genetic loci for LADC risk have been identified by genome-wide association studies (GWAS) and candidate gene association studies. Recently, three GWAS of LADC and subsequent pooled GWAS analyses identified genetic susceptibility variants on chromosome 15q25 (CHRNA), 5p15 (TERT), 3q28 (TP63), 6p21 (BAT3-MSH2 and BTNL2), and 17q.24 (BPTF). SNPs in TERT and TP63 are associated with increased risk for LADC in both never-smokers and smokers, whereas those in CHRNA are associated with increased risk of lung cancer irrespective of histological type. However, the risk alleles for CHRNA SNPs are rare in Asian populations, including Japanese. The association of 5p15 and 3q28 variants with increased risk of LADC was validated in both European and Asian populations; however, strength of association with LADC risk seems different by ethnicity. The association of SNPs in BTNL2 and BPTF with LADC risk was replicated in one study. On the other hand, significant associations of functional variants in DNA repair and metabolic genes have not been reported in lung cancer GWAS. Here, we review previously reported GWAS and candidate gene analyses and discuss identified genetic factors for LADC risk, which may be useful for early detection or prevention of LADC.