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Most significant article published in the Society of Evolution, Medicine and Public Health won Prize: polygenic scores, polygenic adaptation, and human phenotypic differences
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED on 8/30/2020
Analysis of polygenic risk score usage and performance in diverse human populations
A historical tendency to use European ancestry samples hinders medical genetics research, including the use of polygenic scores, which are individual-level metrics of genetic risk. We analyze the first decade of polygenic scoring studies (2008–2017, inclusive), and find that 67% of studies included exclusively European ancestry participants and another 19% included only East Asian ancestry participants. Only 3.8% of studies were among cohorts of African, Hispanic, or Indigenous peoples. We find that predictive performance of European ancestry-derived polygenic scores is lower in non-European ancestry samples (e.g. African ancestry samples: t = −5.97, df = 24, p = 3.7 × 10−6), and we demonstrate the effects of methodological choices in polygenic score distributions for worldwide populations. These findings highlight the need for improved treatment of linkage disequilibrium and variant frequencies when applying polygenic scoring to cohorts of non-European ancestry, and bolster the rationale for large-scale GWAS in diverse human populations.
You might be interested in the paper “interpreting polygenic scores, polygenic adaptation, and human phenotypic differences” by N. Rosenberg, M. Edge, J. Pritchard, and M. Feldman, published in Evolution, Medicine and Public Health (2019). Rosenberg and Pritchard are my former PhD students, both full professors at Stanford, and M.Edge is a student of Rosenberg.
It is my pleasure in my role as President of the International Society for Evolution, Medicine and Public Health to inform you that your 2019 EMPH article, “Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences” has won The George C. Williams Prize which is awarded each year to the first author of the most significant article published in the Society’s flagship journal, Evolution, Medicine and Public Health.
The Prize recognizes the contributions of George C. Williams to evolutionary medicine and aims to encourage and highlight important research in this growing field. It includes $5,000 and an invitation to present at the online lecture series, Club EvMed. The Prize is made possible by donations from Doris Williams, Randolph Nesse, and other supporters of EMPH.
Recent analyses of polygenic scores have opened new discussions concerning the genetic basis and evolutionary significance of differences among populations in distributions of phenotypes. Here, we highlight limitations in research on polygenic scores, polygenic adaptation and population differences. We show how genetic contributions to traits, as estimated by polygenic scores, combine with environmental contributions so that differences among populations in trait distributions need not reflect corresponding differences in genetic propensity. Under a null model in which phenotypes are selectively neutral, genetic propensity differences contributing to phenotypic differences among populations are predicted to be small. We illustrate this null hypothesis in relation to health disparities between African Americans and European Americans, discussing alternative hypotheses with selective and environmental effects. Close attention to the limitations of research on polygenic phenomena is important for the interpretation of their relationship to human population differences.
We are currently witnessing a surge in public interest in the intersection of evolutionary genetics with such topics as cognitive phenotypes, disease, race and heritability of human traits [1–7]. This attention emerges partly from recent advances in genomics, including the introduction of polygenic scores—the aggregation of estimated effects of genome-wide variants to predict the contribution of a person’s genome to a phenotypic trait [8–10]—and a new focus on polygenic adaptations, namely adaptations that have occurred by natural selection on traits influenced by many genes [11–13].
Theories involving natural selection have long been applied in the scientific literature to explain mean phenotypic differences among human populations [14–16]. Although new tools for statistical analysis of polygenic variation and polygenic adaptation provide opportunities for studying human evolution and the genetic basis of traits, they also generate potential for misinterpretation. In the past, public attention to research on human variation and its possible evolutionary basis has often been accompanied by claims that are not justified by the research findings [17]. Recognizing pitfalls in the interpretation of new research on human variation is therefore important for advancing discussions on associated sensitive and controversial topics.
The contribution of polygenic score distributions to phenotype distributions. Two populations are considered, populations 1 (red) and 2 (blue). Each population has a distribution of genetic propensities, which are treated as accurately estimated in the form of polygenic scores (left). The genetic propensity distribution and an environment distribution sum to produce a phenotype distribution (right). All plots have the same numerical scale. (A) Environmental differences amplify an underlying difference in genetic propensities. (B) Populations differ in their phenotypes despite having no differences in genetic propensity distributions. (C) Environmental differences obscure a difference in genetic propensities opposite in direction to the difference in phenotype means. (D) Similarity in phenotype distributions is achieved despite a difference in genetic propensity distributions by an intervention that reduces the environmental contribution for individuals with polygenic scores above a threshold. (E) Within populations, heritability is high, so that genetic variation explains the majority of phenotypic variation; however, the difference between populations is explained by an environmental difference. Panels (A–C and E) present independent normal distributions for genotype and environment that sum to produce normal distributions for phenotype. In (D), (genotype, environment) pairs are simulated from independent normal distributions and a negative constant—reflecting the effect of a medication or other intervention—is added to environmental contributions associated with simulated genotypic values that exceed a threshold
Summary
These limitations illustrate that much of the complexity embedded in use of polygenic scores—the effects of the environment on phenotype and its relationship to genotype, the proportion of variance explained, and the peculiarities of the underlying GWAS data that have been used to estimate effect sizes—is obscured by the apparent simplicity of the single values computed for each individual for each phenotype. Consequently, in using polygenic scores to describe genomic contributions to traits, particularly traits for which the total contribution of genetic variation to trait variation, as measured by heritability, is low—but even if it is high (Fig. 1E)—a difference in polygenic scores between populations provides little information about potential genetic bases for trait differences between those populations.
Unlike heritability, which ranges from 0 to 1 and therefore makes it obvious that the remaining contribution to phenotypic variation is summarized by its difference from 1, the limited explanatory role of genetics is not embedded in the nature of the polygenic scores themselves. Although polygenic scores encode knowledge about specific genetic correlates of trait variation, they do not change the conceptual framework for genetic and environmental contribution to population differences. Attributions of phenotypic differences among populations to genetic differences should therefore be treated with as much caution as similar genetic attributions from heritability in the pre-genomic era.
The mirror self-recognition (MSR) test is commonly used to evaluate nonhuman animals’ self-awareness, and has been reportedly passed by several mammals and birds including apes, elephants, dolphins, and magpies. According to a study published earlier this month (March 11) in TheJournal of Ethology, there’s now evidence to add manta rays to that list.
Contingency checking and self-directed behaviors in giant manta rays: Do elasmobranchs have self-awareness?
Elaborate cognitive skills arose independently in different taxonomic groups. Self-recognition is conventionally identified by the understanding that one’s own mirror reflection does not represent another individual but oneself, which has never been proven in any elasmobranch species to date. Manta rays have a high encephalization quotient, similar to those species that have passed the mirror self-recognition test, and possess the largest brain of all fish species. In this study, mirror exposure experiments were conducted on two captive giant manta rays to document their response to their mirror image. The manta rays did not show signs of social interaction with their mirror image. However, frequent unusual and repetitive movements in front of the mirror suggested contingency checking; in addition, unusual self-directed behaviors could be identified when the manta rays were exposed to the mirror. The present study shows evidence for behavioral responses to a mirror that are prerequisite of self-awareness and which has been used to confirm self-recognition in apes.
X-RAY MAG: How did you become interested in studying the behavior of manta rays?
CA: I knew that I wanted to dedicate my life to study and protect marine life since I was 13 years old. It was during a family vacation in Croatia when I first had the chance to try scuba diving. I was so mesmerized by the experience that when I surfaced I decided to try to find out more about this magical world. I became especially fascinated by the majestic and mysterious manta rays after watching a nature documentary, soon after this first dive. It described how little we know about them and how vulnerable they are.
But growing up in Hungary, a landlocked country, I did not have much option to pursue my dream as a marine biologist, so I got my master’s degree in zoology and my doctorate in neurobiology, while volunteering at oceanography institutes in different countries during the summers. During my PhD studies, I worked on the neuroanatomy and neurohistology of several shark and ray species, including mobulids (mantas and mobulas). During these years, I had the chance to explore the brain structures of mantas and mobulas, which reflected some very unique and surprising features. It was the unusual enlargement of some of their brain parts that got me interested in focusing on their behavior.
“Manta rays are likely the first fish species found to exhibit self-awareness, which implies higher order brain function, as well as sophisticated cognitive and social skills,” study coauthor Csilla Ari told X-Ray Mag.
Observing two rays in a tank at the Atlantis Aquarium in the Bahamas, the researchers noticed that the animals changed their behavior when a mirror was placed on one of the walls. New behaviors included apparently checking out their fins (see this video) and blowing bubbles at their reflections. https://youtu.be/LQ1KErB_2oU
X-RAY MAG: What were the findings that caused you to conclude that these animals are using cognition?
CA: Animal cognition, often referred to as animal intelligence, is an exciting scientific field that attempts to describe the mental capacity of an animal. It developed from the field of comparative psychology and it includes exciting research questions, such as perception, attention, selective learning, memory, spatial cognition, tool use, problem solving or consciousness.
There are no easy ways to test these on manta rays, but I found a widely-used and well-established test that can give us insight on their cognitive abilities. The mirror self-recognition (MSR) test is considered to be a reliable behavioral index to show the animal’s ability for self-recognition/self-awareness. Recognizing oneself in a mirror is a very rare capacity among animals. Only a few, large-brained species have passed this test so far, including Asian elephants, bottlenose dolphins and great apes, but no fish species so far.
So, employing a protocol adapted from primates and bottlenose dolphin MSR studies, I exposed captive manta rays to a large mirror and recorded their behavior. The manta rays showed significantly higher frequency of repetitive behavior, such as circling at the mirror or high frequency cephalic fin movements when the mirror was placed in the tank. Contingency checking and self-directed behavior included body turns into a vertical direction, exposing the ventral side of the body to the mirror while staying visually oriented to the mirror. Most surprisingly, such self-directed behaviors were sometimes accompanied with bubble blowing front of the mirror and sharp downward swims.
“This new discovery is incredibly important,” Marc Bekoff of the University of Colorado in Boulder who was not involved in the study told New Scientist. “It shows that we really need to expand the range of animals we study.”
But the MSR test’s developer, Gordon Gallup of the State University of New York at Albany, told New Scientist that the observed movements might reflect curious, rather than self-aware, behavior. “Humans, chimpanzees, and orangutans are the only species for which there is compelling, reproducible evidence for mirror self-recognition,” he said.
Manta ray hears the dinner bell Norbert Wu/Minden Pictures/FLPA
Giant manta rays have been filmed checking out their reflections in a way that suggests they are self-aware.
Harmless but zippy
Rattlesnakes and other vipers are well-known for their lightning-quick bites, but nonvenomous snakes may be just as speedy, according to a study published this month (March 15) in Biology Letters.
Debunking the viper’s strike: harmless snakes kill a common assumption
To survive, organisms must avoid predation and acquire nutrients and energy. Sensory systems must correctly differentiate between potential predators and prey, and elicit behaviours that adjust distances accordingly. For snakes, strikes can serve both purposes. Vipers are thought to have the fastest strikes among snakes. However, strike performance has been measured in very few species, especially non-vipers. We measured defensive strike performance in harmless Texas ratsnakes and two species of vipers, western cottonmouths and western diamond-backed rattlesnakes, using high-speed video recordings. We show that ratsnake strike performance matches or exceeds that of vipers. In contrast with the literature over the past century, vipers do not represent the pinnacle of strike performance in snakes. Both harmless and venomous snakes can strike with very high accelerations that have two key consequences: the accelerations exceed values that can cause loss of consciousness in other animals, such as the accelerations experienced by jet pilots during extreme manoeuvres, and they make the strikes faster than the sensory and motor responses of mammalian prey and predators. Both harmless and venomous snakes can strike faster than the blink of an eye and often reach a target before it can move.
“There’s this kind of pre-emptive discussion that [vipers] are faster,” study coauthor David Penning of the University of Louisiana, Lafayette, told Smithsonian. But, he added, “as sexy as the topic sounds, there’s not that much research on it.”
To Scientists’ Surprise, Even Nonvenomous Snakes Can Strike at Ridiculous Speeds By Marcus Woo
The Texas rat snake was just as much of a speed demon as deadly vipers, challenging long-held notions about snake adaptations
To put the assumption to the test, Penning and his colleagues used a high-speed camera to film strikes from three snake species—the western cottonmouth and the western diamond-backed rattlesnake (both vipers), and a relatively harmless Texas rat snake that kills its prey using constriction.
When a snake strikes, it literally moves faster than the blink of an eye, whipping its head forward so quickly that it can experience accelerations of more than 20 Gs. “It’s the lynchpin of their strategy as predators,” says Rulon Clark at San Diego State University. “Natural selection has optimized a series of adaptations around striking and using venom that really helps them be effective predators.”
When Penning and his colleagues compared strike speeds in three types of snakes, they found that at least one nonvenomous species was just as quick as the vipers. The results hint that serpents’ need for speed may be much more widespread than thought, which raises questions about snake evolution and physiology. They compared the western cottonmouth and the western diamond-backed rattlesnake, which are both vipers, and the nonvenomous Texas rat snake. They put each snake inside a container and inserted a stuffed glove on the end of a stick. They waved the glove around until the animal struck, recording the whole thing with a high-speed camera. The team tested 14 rat snakes, 6 cottonmouths and 12 rattlesnakes, recording several strikes for each individual.
The recordings revealed that although the highest head acceleration—279 meters per second squared, or nearly 29 g—did indeed come from a rattlesnake, one of the rat snakes followed close behind, accelerating its head at 274 meters per second squared. All the snakes turned out to be speed demons, the team reports this week in Biology Letters. The rattlesnake scored the highest measured acceleration, at 279 meters per second squared. But to their surprise, the nonvenomous rat snake came in a close second at 274 meters per second squared. That’s lightning-quick, considering that a Formula One race car accelerates at less than 27 meters per second squared to go from 0 to 60 in just one second.
“I was really surprised, because this comparison hadn’t been made before,” Rulon Clark of San Diego Statue University who was not involved in the work told Smithsonian. “It’s not that the vipers are slow, it’s that this very high-speed striking ability is something that seems common to a lot of snake species—or a wider array than people might’ve expected.”
Penning told Discover Magazine that the results make sense, since even nonvenomous snakes have to catch their food. “Prey are not passively waiting to be eaten by snakes,” he said.
Rather than offering the snakes some sacrificial prey animals, the researchers baited the snakes into striking in self-defense. They used a stuffed glove on a stick. The glove would move around the snake until the animal realized the glove was “clearly not going away,” Penning says, and struck at it. High-speed cameras and mirrors captured these attacks, which happened in the blink of an eye.
Emerging evidence suggests that both humans and superb fairywrens begin learning the vocal patterns of their mothers even before birth. Now, a study published this month (March 16) in The Auk: Ornithological Advances indicates that the same is true of the red-backed fairywren, offering the possibility of studying the phenomenon across related species.
“Fairywrens have become a new model system in which to test new dimensions in the ontogeny of parent-offspring communication in vertebrates,” study coauthor Mark Hauber of New York City’s Hunter College said in a statement.
Following on their previous discovery of prenatal learning in superb fairywrens, the researchers compared the structure of nestling calls in the red-backed fairywren to the calls of the birds’ mothers. The team found that the more calls per hour that nestlings received when in the egg, the higher the similarity to maternal calls after hatching. (The number of calls received during the nestling period had no effect on call similarity.)
“Prenatal vocal learning has rarely been described in any animal, with the exception of humans and Australian superb fairywrens,” William Feeney of the University of Queensland, Australia, who was not involved in the work said in the statement. “This result is exciting as it opens the door to investigating the taxonomic diversity of this ability, which could provide insights into why it evolves.”
Diane Colombelli-Négrel, Michael S. Webster, Jenélle L. Dowling, Mark E. Hauber, andSonia Kleindorfer (2016) Vocal imitation of mother’s calls by begging Red-backed Fairywren nestlings increases parental provisioning. The Auk: April 2016, Vol. 133, No. 2, pp. 273-285.
Prenatal imitative learning is an emerging research area in both human and non-human animals. Previous studies in Superb Fairywrens (Malurus cyaneus) showed that mothers are vocal tutors to their embryos and that better imitation of maternal calls yields more parental provisions after hatching. To begin to test if such adaptive behavior is widespread amongst Australasian wrens in Maluridae, we investigated maternal in-nest calling patterns in Red-backed Fairywrens (Malurus melanocephalus). We first compared the structure of maternal and nestling call elements. Next, we examined how in-nest calling behavior varied with parental behaviors and ecological contexts (i.e. prevalence of brood parasitism and nest predation). All Red-backed Fairywren females called to their eggs during incubation and they continued to do so for several days after hatching at a lower rate. Embryos that received more calls per hour during the incubation period (but not the nestling period) developed into hatchlings with higher call element similarity between mother and young. Female call rate was mostly independent of nest predation but in years with more interspecific brood parasitism, nestling element similarity was greater and female call rates tended to be higher. Playback experiments showed that broods with higher element similarity to their mother received more successful feeds. The potential for prenatal tutoring and imitative begging calls in 2 related fairywren taxa sets the stage for a full-scale comparative analysis of the evolution and function of these behaviors across Maluridae and in other vocal-learning lineages.
Traveling junk-foodies
White storks may be addicted to junk food, in some cases making migratory trips of tens of kilometers to landfill sites during the breeding season, according to a study published earlier this month (March 15) in Movement Ecology.
“We found that the continuous availability of junk food from landfill has influenced nest use, daily travel distances, and foraging ranges,” study coauthor Aldina Franco of the University of East Anglia said in a statement. “Storks now rely on landfill sites for food—especially during the non-breeding season when other food sources are more scarce.”
Using GPS tracking, the researchers focused on 17 storks traveling between nesting and feeding areas over the course of a year. They found that most long-distance trips were made to landfill sites, and that “having a nest close to a guaranteed food supply also means that the storks are less inclined to leave for the winter,” Franco explained in the statement. “They instead spend their non-breeding season defending their highly desirable nest locations.”
“It’s clear migratory behaviors are quite plastic, in that the [storks] are adaptable and can change quickly,” Andrew Farnsworth of the Cornell Lab of Ornithology who was not involved in the work told National Geographic. He added that the new, detailed dataset will help scientists “consider how such changes in behavior may affect the future population of these birds.”
Are white storks addicted to junk food? Impacts of landfill use on the movement and behaviour of resident white storks (Ciconia ciconia) from a partially migratory population
Nathalie I. Gilbert Email author, Ricardo A. Correia, João Paulo Silva,…, Jenny A. Gill and Aldina M. A. Franco
The migratory patterns of animals are changing in response to global environmental change with many species forming resident populations in areas where they were once migratory. The white stork (Ciconia ciconia) was wholly migratory in Europe but recently guaranteed, year-round food from landfill sites has facilitated the establishment of resident populations in Iberia. In this study 17 resident white storks were fitted with GPS/GSM data loggers (including accelerometer) and tracked for 9.1 ± 3.7 months to quantify the extent and consistency of landfill attendance by individuals during the non-breeding and breeding seasons and to assess the influence of landfill use on daily distances travelled, percentage of GPS fixes spent foraging and non-landfill foraging ranges. Results Resident white storks used landfill more during non-breeding (20.1 % ± 2.3 of foraging GPS fixes) than during breeding (14.9 % ± 2.2). Landfill attendance declined with increasing distance between nest and landfill in both seasons. During non-breeding a large percentage of GPS fixes occurred on the nest throughout the day (27 % ± 3.0 of fixes) in the majority of tagged storks. This study provides first confirmation of year-round nest use by resident white storks. The percentage of GPS fixes on the nest was not influenced by the distance between nest and the landfill site. Storks travelled up to 48.2 km to visit landfills during non-breeding and a maximum of 28.1 km during breeding, notably further than previous estimates. Storks nesting close to landfill sites used landfill more and had smaller foraging ranges in non-landfill habitat indicating higher reliance on landfill. The majority of non-landfill foraging occurred around the nest and long distance trips were made specifically to visit landfill. Conclusions The continuous availability of food resources on landfill has facilitated year-round nest use in white storks and is influencing their home ranges and movement behaviour. White storks rely on landfill sites for foraging especially during the non-breeding season when other food resources are scarcer and this artificial food supplementation probably facilitated the establishment of resident populations. The closure of landfills, as required by EU Landfill Directives, will likely cause dramatic impacts on white stork populations.
WEIRD & WILDJunk Food-Loving Birds Diss Migration, Live on Landfill By Brian Handwerk
Spain and Portugal’s white storks are forgoing their annual journeys to African wintering grounds, a new study says
You’ve heard of the staycation. Some white storks in Europe are now opting for the staygration.
The big birds are skipping their annual trip to African wintering grounds to remain year-round in Spain and Portugal, a new study shows.
Why? They’ve developed an addiction to junk food at landfills.
“White storks used to be wholly migratory. Before the 1980s, there were no white storks staying in” Spain and Portugal, says study leader Aldina Franco, a conservation ecologist at the University of East Anglia in the U.K.
Israel’s barren Negev desert is home to striped hyenas and gray wolves—two large scavenger species with considerably overlapping diets. But although such conditions might be expected to create fierce competition, researchers in Israel and the U.S. have now presented evidence that—at least in some cases—these animals form alliances and may even hunt collaboratively for food. The findings were published last month (February 10) in Zoology in the Middle East.
Wolves and hyenas in the desert might “just need each other to survive, because food is so, so limited,” study coauthor Vladimir Dinets of the University of Tennessee in Knoxville told The Washington Post.
Collating observations made over the past two decades (including reports of overlapping paw prints, and sightings of hyenas among packs of wolves), the researchers note that the findings could reflect the behavior of a few, oddly behaving hyenas, or a more widespread commensal, or even cooperative, relationship between the species.
“Animal behavior is often more flexible than described in textbooks,” Dinets said in a press release. “When necessary, animals can abandon their usual strategies and learn something completely new and unexpected. It’s a very useful skill for people, too.”
Mathematicians developed a solution to Selye’s riddle which has puzzled scientists for almost 80 years.
In previous research, it was suggested that adaptation of an animal to different factors looks like spending of one resource, and that the animal dies when this resource is exhausted. In 1938, Hans Selye introduced “adaptation energy” and found strong experimental arguments in favor of this hypothesis. However, this term has caused much debate because, as it cannot be measured as a physical quantity, adaptation energy is not strictly energy.
Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death
• We formalize Selye׳s ideas about adaptation energy and dynamics of adaptation.
• A hierarchy of dynamic models of adaptation is developed.
• Adaptation energy is considered as an internal coordinate on the ‘dominant path’ in the model of adaptation.
• The optimal distribution of resources for neutralization of harmful factors is studied.
• The phenomena of ‘oscillating death’ and ‘oscillating remission’ are predicted.
In previous research, it was suggested that adaptation of an animal to different factors looks like spending of one resource, and that the animal dies when this resource is exhausted.
In 1938, Selye proposed the notion of adaptation energy and published ‘Experimental evidence supporting the conception of adaptation energy.’ Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description.
We aim to demonstrate that Selye׳s adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye׳s axioms of adaptation energy together with Goldstone׳s modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the ‘dominant path’ in the model of adaptation. The phenomena of ‘oscillating death’ and ‘oscillating remission’ are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors.
In this work, an international team of researchers, led by Professor Alexander N. Gorban from the University of Leicester, have developed a solution to Selye’s riddle, which has puzzled scientists for almost 80 years.
Alexander N. Gorban, Professor of Applied Mathematics in the Department of Mathematics at the University of Leicester, said: “Nobody can measure adaptation energy directly, indeed, but it can be understood by its place already in simple models. In this work, we develop a hierarchy of top-down models following Selye’s findings and further developments. We trust Selye’s intuition and experiments and use the notion of adaptation energy as a cornerstone in a system of models. We provide a ‘thermodynamic-like’ theory of organism resilience that, just like classical thermodynamics, allows for economics metaphors, such as cost and bankruptcy and, more importantly, is largely independent of a detailed mechanistic explanation of what is ‘going on underneath’.”
Adaptation energy is considered as an internal coordinate on the “dominant path” in the model of adaptation. The phenomena of “oscillating death” and “oscillating remission,” which have been observed in clinic for a long time, are predicted on the basis of the dynamical models of adaptation. The models, based on Selye’s idea of adaptation energy, demonstrate that the oscillating remission and oscillating death do not need exogenous reasons. The developed theory of adaptation to various factors gives the instrument for the early anticipation of crises.
Professor Alessandro Giuliani from Istituto Superiore di Sanità in Rome commented on the work, saying: “Gorban and his colleagues dare to make science adopting the thermodynamics style: they look for powerful principles endowed with predictive ability in the real world before knowing the microscopic details. This is, in my opinion, the only possible way out from the actual repeatability crisis of mainstream biology, where a fantastic knowledge of the details totally fails to predict anything outside the test tube.1”
Citation: Alexander N. Gorban, Tatiana A. Tyukina, Elena V. Smirnova, Lyudmila I. Pokidysheva. Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death. Journal of Theoretical Biology, 2016; DOI:10.1016/j.jtbi.2015.12.017. Voosen P. (2015) Amid a Sea of False Findings NIH tries Reform, The Chronicle of Higher Education.
Bone is a highly dynamic tissue that responds to changes in its external environment. Our bones adapt their mass and architecture according to the external mechanical loading conditions. Any long term alterations in loading conditions result in alteration of bone mass and architecture. This is highlighted in the following examples:
Astronauts tend to lose their bone when they are in space. This is because the bones are not mechanically loaded externally due to absence of or reduction in gravitational force.
Tennis players gain more mass in their playing forearm as compared to the non-playing forearm.
In both these examples bones tend to readjust their internal structural mass and alignment as per the external loads or their absence. How bones can achieve this? How bone forming and bone resorbing cells can be orchestrated to bring about this adaptation?
Bone cells
The questions mentioned above can be answered by knowing more about the cellular components of bone and their functions. Our bones primarily have four cell types: osteocytes, osteoblasts, osteoclasts and bone lining cells. Osteocytes are believed to be the ‘professional’ mechanosensors of bone i.e. they sense the external loads put on bone. Osteoblasts are the bone forming cells. Osteoclasts are the bone resorbing cells and as the name suggests, bone lining cells line the bone surfaces and play a role in regeneration of osteogenic cells. Osteocytes, following mechanical loading, secrete signalling molecules such as nitric oxide (besides others). These signalling molecules then modulate the activity of bone forming osteoblasts and/or bone resorbing osteoclasts. Thus osteocytes orchestrate this process wherein adequate bone mass and architecture is achieved in accordance with the external loading conditions.
Anatomically, the osteocytes reside with in the hard bony matrix. They are the majority cell types in bone and are ideally placed to sense the mechanical loads. Osteocytes have a cell body and from the cell body arise nearly fifty cell processes. Through these cell processes each osteocyte forms a network with the surrounding osteocytes. Through this network, following mechanical loading, osteocytes can stimulate the activity of osteoblasts and inhibit the activity of osteoclasts. This process of maintenance of bone mass and architecture is called bone remodelling. Bone remodelling occurs through out our life. It occurs in response to microfractures, which can appear in our bone without being noticed clinically. As long as our bone metabolism is physiologically normal these stimuli, such as microfractures, result in bone remodelling.
In diseases such as osteoporosis, the mechanism of bone remodelling is disrupted and there is more bone resorbtion than new bone formation thus leading to reduction in bone mass and alteration of bone architecture. Drug therapies for osteoporosis such as bisphosphonates, act by inhibiting the activity of osteoclasts thereby resulting in reduction in bone resorbtion and hence helping in maintenance of adequate bone mass and architecture. Newer therapies that target to modulate a part of bone remodelling are being investigated.
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