Thrifty phenotype

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The thrifty phenotype hypothesis says that reduced fetal growth is strongly associated with a number of chronic conditions later in life. This increased susceptibility results from adaptations made by the fetus in an environment limited in its supply of nutrients. The thrifty phenotype is a component of the fetal origins hypothesis. These chronic conditions include coronary heart disease, stroke, diabetes, and hypertension.

Contents

Evolutionary rationale

Benefit for offspring

Proponents of this idea say that in poor nutritional conditions, a pregnant woman can modify the development of her unborn child such that it will be prepared for survival in an environment in which resources are likely to be short, resulting in a thrifty phenotype (Hales & Barker, 1992 [1] [2] ). It is sometimes called Barker's hypothesis, after Professor David J. P. Barker, researching at the University of Southampton who published the theory in 1990. [3]

The thrifty phenotype hypothesis suggests that early-life metabolic adaptations help in survival of the organism by selecting an appropriate trajectory of growth in response to environmental cues. Recently, some scientists have proposed that the thrifty phenotype prepares the organism for its likely adult environment in long term.

Benefit for mother

However, environmental changes during early development may result in the selected trajectory becoming inappropriate, resulting in adverse effects on health. This paradox generates doubts about whether the thrifty phenotype is adaptive for human offspring. Thus, the thrifty phenotype should be considered as the capacity of all offspring to respond to environmental cues during early ontogenetic development. It has been suggested that the thrifty phenotype is the consequence of three unlike adaptive processes: maternal effects, niche construction and developmental plasticity, which all are influenced by the brain. While developmental plasticity demonstrates an adaptation by the offspring, niche construction and parental effects are result of parental selections rather than offspring fitness. Therefore, the thrifty phenotype can be described as a manipulation of offspring phenotype for the benefit of maternal fitness. The information that enters offspring phenotype during early development mirror the mother’s own developmental experience and the quality of the environment during her own maturation rather than predicting the possible future environment of the offspring [4]

Adverse effects

Many human diseases in adulthood are related to growth patterns during early life, determining early-life nutrition as the underlying mechanism. Individuals with a thrifty phenotype will have "a smaller body size, a lowered metabolic rate and a reduced level of behavioural activity… adaptations to an environment that is chronically short of food" (Bateson & Martin, 1999 [5] ). Those with a thrifty phenotype who actually develop in an affluent environment may be more prone to metabolic disorders, such as obesity and type II diabetes, whereas those who have received a positive maternal forecast will be adapted to good conditions and therefore better able to cope with rich diets. This idea (Barker, 1992 [6] ) is now widely (if not universally) accepted and is a source of concern for societies undergoing a transition from sparse to better nutrition (Robinson, 2001 [7] ).

Risk factors of thrifty phenotype include advanced maternal age and placental insufficiency. [8]

Molecular mechanisms

The ability to conserve, acquire and expend energy is believed to be an innate, ancient trait that is imbedded in the genome in a way that is quite protected against mutations. [9] These changes are also believed to possibly be inherited across generations. [9] Leptin has been identified as a possible gene for the acquisition of these thrifty traits. [9]

On a larger anatomic scale, the molecular mechanisms are broadly caused by a suboptimal environment in the reproductive tract or maternal physiological adaptations to pregnancy. [8]

See also

Related Research Articles

Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin.

Intrauterine growth restriction

Intrauterine growth restriction (IUGR) refers to poor growth of a fetus while in the mother's womb during pregnancy. The causes can be many, but most often involve poor maternal nutrition or lack of adequate oxygen supply to the fetus.

Hypothalamic–pituitary–adrenal axis Set of physiological feedback interactions

The hypothalamic–pituitary–adrenal axis is a complex set of direct influences and feedback interactions among three components: the hypothalamus, the pituitary gland, and the adrenal glands.

A maternal effect is a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother. In genetics, maternal effects occur when an organism shows the phenotype expected from the genotype of the mother, irrespective of its own genotype, often due to the mother supplying messenger RNA or proteins to the egg. Maternal effects can also be caused by the maternal environment independent of genotype, sometimes controlling the size, sex, or behaviour of the offspring. These adaptive maternal effects lead to phenotypes of offspring that increase their fitness. Further, it introduces the concept of phenotypic plasticity, an important evolutionary concept. It has been proposed that maternal effects are important for the evolution of adaptive responses to environmental heterogeneity.

Small for gestational age

Small for gestational age (SGA) newborns are those who are smaller in size than normal for the gestational age, most commonly defined as a weight below the 10th percentile for the gestational age.

Phenotypic plasticity Trait change of an organism in response to environmental variation

Phenotypic plasticity refers to some of the changes in an organism's behavior, morphology and physiology in response to a unique environment. Fundamental to the way in which organisms cope with environmental variation, phenotypic plasticity encompasses all types of environmentally induced changes that may or may not be permanent throughout an individual's lifespan. The term was originally used to describe developmental effects on morphological characters, but is now more broadly used to describe all phenotypic responses to environmental change, such as acclimation (acclimatization), as well as learning. The special case when differences in environment induce discrete phenotypes is termed polyphenism.

Neurodevelopmental disorders are a group of disorders that affect the development of the nervous system, leading to abnormal brain function which may affect emotion, learning ability, self-control, and memory. The effects of neurodevelopmental disorders tend to last for a person's lifetime.

Protein–energy malnutrition

Protein–energy malnutrition (PEM), sometimes called protein-energy undernutrition (PEU), is a form of malnutrition that is defined as a range of pathological conditions arising from coincident lack of dietary protein and/or energy (calories) in varying proportions. The condition has mild, moderate, and severe degrees.

The thrifty gene hypothesis, or Gianfranco's hypothesis is an attempt by geneticist James V. Neel to explain why certain populations and subpopulations in the modern day are prone to diabetes mellitus type 2. He proposed the hypothesis in 1962 to resolve a fundamental problem: diabetes is clearly a very harmful medical condition, yet it is quite common, and it was already evident to Neel that it likely had a strong genetic basis. The problem is to understand how disease with a likely genetic component and with such negative effects may have been favoured by the process of natural selection. Neel suggested the resolution to this problem is that genes which predispose to diabetes were historically advantageous, but they became detrimental in the modern world. In his words they were "rendered detrimental by 'progress'". Neel's primary interest was in diabetes, but the idea was soon expanded to encompass obesity as well. Thrifty genes are genes which enable individuals to efficiently collect and process food to deposit fat during periods of food abundance in order to provide for periods of food shortage.

Placental insufficiency or utero-placental insufficiency is the failure of the placenta to deliver sufficient nutrients to the fetus during pregnancy, and is often a result of insufficient blood flow to the placenta. The term is also sometimes used to designate late decelerations of fetal heart rate as measured by cardiotocography or an NST, even if there is no other evidence of reduced blood flow to the placenta, normal uterine blood flow rate being 600mL/min.

Metabolic imprinting refers to the epigenetic programming of metabolism during the pre-natal and neo-natal periods, which can have significant consequences later on in an organism's life.

Prenatal nutrition

Prenatal nutrition addresses nutrient recommendations before and during pregnancy. Nutrition and weight management before and during pregnancy has a profound effect on the development of infants. This is a rather critical time for healthy development since infants rely heavily on maternal stores and nutrient for optimal growth and health outcome later in life.

Nutriepigenomics is the study of food nutrients and their effects on human health through epigenetic modifications. There is now considerable evidence that nutritional imbalances during gestation and lactation are linked to non-communicable diseases, such as obesity, cardiovascular disease, diabetes, hypertension, and cancer. If metabolic disturbances occur during critical time windows of development, the resulting epigenetic alterations can lead to permanent changes in tissue and organ structure or function and predispose individuals to disease.

Transgenerational epigenetic inheritance

Transgenerational epigenetic inheritance, (TEI), is the transmission of epigenetic markers from one organism to the next that affects the traits of offspring without alteration of the primary structure of DNA —in other words, epigenetically. The less precise term "epigenetic inheritance" may cover both cell–cell and organism–organism information transfer. Although these two levels of epigenetic inheritance are equivalent in unicellular organisms, they may have distinct mechanisms and evolutionary distinctions in multicellular organisms.

Developmental Origins of Health and Disease is an approach to medical research emphasizing the role of prenatal and perinatal exposure to environmental factors, such as undernutrition, in determining the development of human diseases in adulthood. This approach includes an emphasis on epigenetic causes of adult chronic diseases, including the potential for such environmental causes to influence disease risk across generations.

A predictive adaptive response (PAR) is a developmental trajectory taken by an organism during a period of developmental plasticity in response to perceived environmental cues. This PAR does not confer an immediate advantage to the developing organism; however, if the PAR correctly anticipates the postnatal environment it will be advantageous in later life, if the environment the organism is born into differs from that anticipated by the PAR it will result in a mismatch. PAR mechanisms were first recognized in research done on human fetuses that investigated whether poor nutrition results in the inevitable diagnosis of Type 2 diabetes in later life. PARs are thought to occur through epigenetic mechanisms that alter gene expression, such as DNA methylation and histone modification, and do not involve changes to the DNA sequence of the developing organism. Examples of PARs include greater helmet development in Daphnia cucullata in response to maternal exposure to predator pheromones, rats exposed to glucocorticoid during late gestation led to an intolerance to glucose as adults, and coat thickness determination in vole pups by the photoperiod length experienced by the mother. Two hypotheses to explain PAR are the "thrifty phenotype" hypothesis and the developmental plasticity hypothesis.

Karen A. Lillycrop is a professor of Epigenetics at the University of Southampton in the UK. She is listed as a notable scientist in Thomson Reuters' Highly Cited Researchers 2014, ranking her among the top 1% most cited scientists.

The fetal origins hypothesis proposes that the period of gestation has significant impacts on the developmental health and wellbeing outcomes for an individual ranging from infancy to adulthood. The effects of fetal origin are marked by three characteristics: latency, wherein effects may not be apparent until much later in life; persistency, whereby conditions resulting from a fetal effect continue to exist for a given individual; and genetic programming, which describes the 'switching on' of a specific gene due to prenatal environment. Research in the areas of economics, epidemiology, and epigenetics offer support for the hypothesis.

Intragenomic and intrauterine conflicts in humans arise between mothers and their offspring. Parental investment theory states that parents and their offspring will often be in conflict over the optimal amount of investment that the parent should provide. This is because the best interests of the parent do not always match the best interests of the offspring. Maternal-infant conflict is of interest due to the intensity of maternal investment in her offspring. In humans, mothers often invest years of care into their children due to the long developmental period before children become self-sufficient. 

Fetal programming, also known as prenatal programming, is a theory which suggests that the environment surrounding the fetus during its developmental phase, plays a seminal role in determining its disease risk during the later stages.

References

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  2. Hales, CN; Barker, DJ (2001). "The thrifty phenotype hypothesis". British Medical Bulletin. 60: 5–20. doi: 10.1093/bmb/60.1.5 . PMID   11809615.
  3. Barker, D.J.P. (1997). "Maternal Nutrition, Fetal Nutrition, and Disease in Later Life". Nutrition, '13', pg. 807
  4. Wells JC (February 2007). "The thrifty phenotype as an adaptive maternal effect". Biol Rev Camb Philos Soc. 82 (1): 143–72. doi:10.1111/j.1469-185X.2006.00007.x. PMID   17313527.
  5. Martin, Paul; Bateson, Patrick (1999). Design for a life: How behaviour develops. London: Jonathan Cape. pp. 110–1. ISBN   0-224-05064-8.
  6. Barker, D. J. P., ed. (1992). Fetal and infant origins of adult disease. London: British Medical Journal. ISBN   0-7279-0743-3.
  7. Robinson R (February 2001). "The fetal origins of adult disease : No longer just a hypothesis and may be critically important in south Asia". BMJ. 322 (7283): 375–6. doi:10.1136/bmj.322.7283.375. PMC   1119617 . PMID   11179140. Editorial
  8. 1 2 Aiken, C. E.; Ozanne, S. E. (2013). "Transgenerational developmental programming". Human Reproduction Update. 20 (1): 63–75. doi: 10.1093/humupd/dmt043 . PMID   24082037.
  9. 1 2 3 Stöger R (February 2008). "The thrifty epigenotype: an acquired and heritable predisposition for obesity and diabetes?". BioEssays. 30 (2): 156–66. doi:10.1002/bies.20700. PMID   18197594.