Olfactory receptor genes have more variation than most gene families in the human genome. The only family with greater diversity is the major histocompatibility complex (MHC). Both families also exhibit high heterozygosity. Due to its association with disease, the MHC is well-studied. The explanation for the maintenance of MHC diversity is pathogen-driven selection–either through heterozygote advantage or frequency-dependent selection (see here for a review); a small number of papers (here’s two: 1 and 2) have also argued for divergent allele advantage. A diversity of pathogens will result in a diversity of MHC genes over time; as a species develops resistance to a disease, an evolutionary respones occurs in the disease-causing agent. The common analogy is the evolutionary arms race, also called the Red Queen Hypothesis.
If we apply that same model to olfaction in light of a few recent findings. there might be something worth pursuing. We know we can smell millions of odors. Such a diversity of odorants in the environment that vary from region to region may result in incredible diversity in the human olfactory receptor subgenome–especially if we look at it from the perspective of divergent allele advantage.
This research is a bit old (October 2013) but recently caught my eye:
Research out of Japan shows that walking in the woods also may play a role in fighting cancer. Plants emit a chemical called phytoncides that protects them from rotting and insects. When people breathe it in, there is an increase in the level of “natural killer” cells, which are part of a person’s immune response to cancer.
“When we walk in a forest or park, our levels of white blood cells increase and it also lowers our pulse rate, blood pressure and level of the stress hormone cortisol,” Michelfelder said.
There is rare evidence of cancer (osteocarcanoma) in prehistoric hunter-gatherer populations (see here for a nice public science summary) and mummies (another public science review is found here). This may be because we can’t detect it and accurately determine its frequency. Modern techniques like CT scanning make inroads into non-invasive paleopathology data gathering but skeletons have a limited capacity to reveal diseases of the past. This is partly because the lesions (like most pathologies) often don’t reach the bones, take too long to reach the bones before death, or are nonspecific.
The rarity of evidence for cancer may also be because it simply wasn’t there. Most cancers occur at the end of of or after reproductive years; the shorter human life span ‘in the wild’ would likely lead to fewer cases of cancer experienced by our prehistoric relatives and not impact net reproductive success (meaning any cancer-causing genes would persist in human populations). Persistent cancer-causing genes interact with the modern environment and longer life span to reach modern cancer frequencies. I wonder if lifestyles that take one into the woods for significant periods of time (e.g., prehistoric hunter-gatherers, modern populations leading ‘traditional’ lifestyles) reduce cancer incidence?
I am reminded of something I heard when I was a kid about the actor Dirk Benedict (from Battlestar Galactica–the original Starbuck!–and the A-Team) having had overcome prostate cancer by disappearing into the woods and the wilds of the country and eating a macrobiotic diet. I looked up his story to see if I remembered correctly. I had mostly:
When I learned I had a tumor—I refused to be tested for malignancy—I weighed 180 pounds. When I came out of the mountains of New Hampshire six weeks later, I weighed 155. I went to stay in a friend’s cabin because I didn’t want any distractions, any temptations, anybody calling up to say, “Let’s go have a bagel.” Well, all hell broke loose. Some days I felt on top of the world, and other days I couldn’t get out of bed. Sometimes I couldn’t walk up the stairs, and sometimes I’d ride, run and chop wood for 24 hours.
I never did go into a hospital. Instead, I packed up my duffel bag and became a vagabond, traveling to Montana, Maine, California, New York City, Wisconsin, hitchhiking across the country once and driving across twice.
Did the woods help? Maybe! The sense of smell–yet another benefit!
A new study (published here) suggest that scientists unable to replicate behavioral studies in rats and mice may be due to the presence of male researchers.
The presence of male experimenters produced a stress response in mice and rats equivalent to that caused by restraining the rodents for 15 minutes in a tube or forcing them to swim for three minutes. This stress-induced reaction made mice and rats of both sexes less sensitive to pain.
The chemical signals emitted by males of any species are detectable by other species. Since males secrete these pheromones at higher concentrations than women, the effects tend to be limited to male researchers. Rats and mice acclimatize over time to the male researchers, suggesting an ‘easing’ in period prior to experimentation or perhaps, even better, even more effort to promote women in science!
Since there is growing evidence that humans respond to pheromones, I wonder if there is a similar effect caused by male researchers on human subjects; namely, is stress induced in males and females when experiments are conducted by men? Outside the lab, does the scent of a man induce stress and reduce pain response, but in a good way? I’ll end with ‘Boys‘ by Robots in Disguise.
Between 6000-4000 years ago (according to study published in Nature Communications), indigenous Mesolithic hunter-gatherers acquired pigs from Neolithic farmers immigrating to Europe. I have been interested in Pleistocene pigs for a while (and their continued association with humans into the Holocene). The reason for my interest is that pigs produce a lot of androstenone (a sex steroid), especially males, and humans vary in their genotypic/phenotypic perception of androstenone.
Human variation in androstenone perception depends on two non synonymous SNPs (Keller et al. 2007), R88W and T133M. These SNPs appear to play a role in meat preference: Lunde et al. (2012) found that wild type humans (RT/RT) rated the meat of non-castrated male pigs less favorably than those with variant alleles (RT/WM and WM/WM). HapMap and 1000 Genomes are great resources but do not capture the variation local human populations, let alone the anthropological underpinnings of variation. In my lab and using a wide mix of global human populations, I found significant variation in androstenone perception frequencies, with higher frequencies of mutations throughout Eurasia–an area heavily invested in pig meat throughout human prehistory; in Japanese and Northern Europeans, the frequency of homozygote recessive mutations is much higher and these areas have a rich history with pigs–especially Japan.
Currently, I am working through the archaeological data for human-pig interaction in Europe and Asia (with a special focus on Asia as the origin of all pigs–see here and here for starting places) to interpret the results of the genetic data. Both the archaeological data and genetic data are thin when taken across such a huge space but they are a starting point; a neat study would be to find a locale with a rich archaeological record, human population to test for the gene and perception, and a good ethnohistory on the relationship with pigs–something I am working on right now.
Combining data from the archaeological record and the genetic history of human populations adds depth to what could, on their own, be interesting but uncontextual datasets. Taken together, these datasets can paint a more detailed picture of the evolutionary inter-relationship between genes and diet.
Recent advances in the field of paleogenomics (the study of ancient genomes) have uncovered the story of inter-species mating in those early days out of Africa before dispersal into Eurasia. Prior to these studies we’ve had little evidence supporting either cultural interaction with archaic humans or inter-breeding.
Clandestine trysts or common practice? The draft sequence of the Neanderthal genome published in 2010 revealed that we mated with Neanderthals in the Near East enough to share 1-4% of our DNA with them. On the heels of the draft sequence of the Neandertal genome, the same team published the Denisovan genome using DNA extracted from an exceptionally preserved finger bone from remains found in Denisova Cave in Siberia. The archaeological data at Denisova show a mixed toolkit with elements of Upper- and Middle-Paleolithic industries. Molar morphology indicated Denisovans were distinct from both modern and known archaic humans. The genomic data indicate Denisovans were indeed a new species with unique genomic markers. The power of modern genomics allows us to also find evidence of mating with modern humans, specifically modern Melanesians who share 4-6% of their genomes with Denisovans. Were these matings clandestine trysts or was there more at stake—some flow of genes to modern humans that helped us adapt to the novel environments of Europe and Asia?
Genomic breadcrumbs? Preliminary comparisons between Neandertal and human genes indicate significant differences in aspects of cognition, metabolism, and skeletal and skin morphology. But what about the inherited portion of the genome? Does it have a role in any functional aspect of our biology and physiology? Dr. Green, lead author on the draft sequence of the Neandertal genome described the inherited portion as ‘sparsely distributed across the genome, just a ‘bread crumbs’ clue of what happened in the past’. But two new papers tell a different story, suggesting that inter-breeding may have significantly contributed to successful adaptation to the new environments of Eurasia.
In the summer of 2011, another team identified a Neandertal origin for a unique cluster of co-inherited gene variants (a haplotype) in the non-coding segment of the dystrophin gene on the X-chromosome. This haplotype occurs at a frequency of 9% in all modern non-African human populations and likely first appeared in the genome prior to or very early in the migration out of Africa. The authors of the study posit that either this genetic (and/or cultural) exchange enabled successful modern human adaptations to the novel environments of Eurasia. There is an intriguing possibility that human males left Africa in greater numbers and mated with archaic females: an earlier study on modern human variation found the X-chromosome experienced more than expected genetic drift at the time of human migration out of Africa, a pattern not found in the migrations into East Asia and Europe.The authors of this study conclude that female effective population size was reduced compared to males due to some sex-biased process or natural selection affecting the X-chromosome in non-African populations.
Speculations that inherited genomic material conferred a fitness advantage gained further ground in a study published this summer in Nature. A Stanford University team identified HLA gene variants that are rare in modern Africans but significantly present in West Asians, again suggesting genetic admixture outside Africa prior to Eurasian expansion. HLA class I genes are critical to the immune system because they target and destroy pathogens. The authors of the study argue that inter-breeding restored HLA diversity that was reduced by a population bottleneck in migration out of Africa, citing examples of similar events in the evolutionary genetic history of the peopling of the Americas. Not only was diversity restored to modern humans but new immune variants specifically adapted to local pathogens may have been acquired in the process as well. HLA-A*11 (associated with Epstein-Barr virus protection), for example, has become a dominant form in non-African populations occurring at rates of 64% in East Asia and Oceania (and even more in Papua New Guinea) suggesting strong selection. The high frequency of these gene variants (as compared with other regions of the genome) may be explained by the need for the immune system to be flexible to new pathogens (particularly rapidly evolving viruses), rendering it more susceptible to the forces of natural selection.
The future of the past. If the data from these various studies is supported by future work, we may end up rethinking our relationship to our closest cousins – were we separate species? Even field biologists who have the array of genes, biology, physiology and behavior sometimes have trouble determining whether two groups be classed as separate species or not. For those working in paleoanthropology or paleogenomics, the dataset is even more limited and the creation of new taxa is temporary pending further data but useful as a heuristic tool.
The field of paleogenomics is relatively young and has a tremendous number of methodological and technical challenges to overcome before we can comfortably say that the sequences yielded are authentic and reliably represent the genetic data. A major challenge is verifying and authenticating the endogenous (or local) DNA in a specimen that has been potentially contaminated by microbes and human researchers. The past decade has been punctuated by marvelous advances that have helped us better understand recent human evolution and ourselves. The possibility that our advantage in global colonization derives from early acts of inter-breeding is a fascinating one. With the rapid advancements in technology and increased interest in ancient DNA, the future looks promising for unraveling the story of the immediate past.
- Green, R. E. et al., Science 328, 710 (2010).
- Reich, D. et al., Nature 468, 1053 (2010).