ISSN: 2074-8132
ISSN: 2074-8132
En Ru
Modern interpretations of evolutionary, anthropological and ecological aspects of the “thrifty genotype” hypothesis

Modern interpretations of evolutionary, anthropological and ecological aspects of the “thrifty genotype” hypothesis

Recieved: 09/18/2023

Accepted: 10/09/2023

Published: 11/20/2023

Keywords: thrifty genotype; metabolic diseases; genetic diversity; anthropological diversity; natural selection; gene alleles; ecology

To cite this article

Kozlov Andrew I., Gasanov Eugeni V., Parfenteva Olga I. Modern interpretations of evolutionary, anthropological and ecological aspects of the “thrifty genotype” hypothesis. // Lomonosov Journal of Anthropology 2023. Issue 4. 47-57 https://doi.org/10.32521/2074-8132.2023.4.047-057.

This work is licensed under a Creative Commons: Attribution 4.0 International (CC BY 4.0). (CC BY 4.0). (https://creativecommons.org/licenses/by/4.0/deed.ru)
Issue 4, 2023

Abstract

Introduction. There are a number of genes, individual alleles of which or their combinations make the carrier susceptible to the disease. In the case of type 2 diabetes, obesity, and metabolic syndrome, the hypothesis of a “thrifty genotype” was put forward as a combination of gene alleles that provided their carriers with advantages in the prehistoric and historical past, but provoked morbidity now. Such a genotype should have previously been under the positive selection, whereas in the modern world it may play a negative role. It is also obvious that the expression of the thrifty genotype as well as the genes that form it and their alleles, should depend on anthropological and ecological conditions: the ecology of the region where the human population lives and their traditional subsistence and farming systems.

The aim of the proposed review is to systematize modern views on the problem of thrifty genotype with special attention to the evolutionary anthropological, and ecological aspects of the problem.

Materials and methods. Herein we represent a review of current data regarding the thrifty genotype hypothesis. The paper reviews the main theses of the hypothesis, its basis, and the arguments of supporters and critics. The evolutionary, anthropological, and ecological aspects of the thrifty genotype hypothesis are discussed.

Results. A significant number of experimental studies and reviews give an idea of the distribution of thrifty genotypes in populations of different origins and anthropological affiliations. However, the coverage of material and inclusion of population data in the analysis is uneven. The genetic geography of thrifty genotypes remains poor and, commonly, insufficiently studied. The most complete and methodologically correct systematization of primary materials on the prevalence of thrifty genotypes, their connection with the ecological conditions of the natural environment, and anthropogenic factors, including traditional subsistence and farming systems and the nature of nutrition, remains still relevant.

Conclusion. We consider the integrated ecological approach to be the most promising direction of theoretical research on the problem of “thrifty genotype”. The approach from the standpoint of the concept of “niche construction” removes the seeming contradictions between the main hypotheses considered in our review – the thrifty genotype, the drifty genotype and the thrifty phenotype. © 2023. This work is licensed under a CC BY 4.0 license.

References

Bondareva E.A., Parfenteva O.I., Sonkin V.D. “Beregliviy” genotype: ozirenie ili sportivnii uspech [“Thrifty” genotype: obesity or success in sport]. Moscow University Anthropology Bulletin [Vestnik Moscovskogo Universiteta. Seriya XXIII. Antropologia], 2017, 3, pp 56–67. (In Russ.).

Borovkova N.P., SheremetyevaV.A., Evsyukov A.N., Spitsyn V.A. Zaconomernosti raspredeleniya allele apolipoproteina E (APOE) sredi mirovogo narodonaseleniya [Frequency distribution of apolipoprotein e (apoe) alleles in world population] Moscow University Anthropology Bulletin [Vestnik Moscovskogo Universiteta. Seriya XXIII. Antropologia], 2010, 2, pp. 21–35. (In Russ.).

Gasanov E.V. [Hybridization events in the human evolution]. Moscow University Anthropology Bulletin [Vestnik Moscovskogo Universiteta. Seriya XXIII. Antropologia], 2022, 3, pp. 72–85. (In Russ.) DOI: 10.32521/2074-8132.2022.3.072-085.

Kozlov A.I. Izmenenie genofonda severnich populacii; “zakat etnosov” ili formirovanie novoi adaptivnoi gruppi? [Changing of a gene pool with northern populations: «the dawn of ethnoses» or formation of a new adaptive group?]. Vestnik arheologii, antropologii i etnografii [Archaeology, Anthropology and Ethnography Bulletin], 2014, 3, pp. 99–107. (In Russ.).

Kozlov A.I., Balanovsky O.P., Vershubskaya G.G., Gorin I.O., Balanovska E.V. et al. Geneticheski determinirovannaia nedostatochnost tregalasi v razlichnich gruppach naselenia Rossii I sopredelnich stran [Genetically determined trehalase deficiency in various population groups of Russia and neighboring countries]. Voprosi Pitania [Problems of nutrition], 2021, 90 (5), pp. 96–103. (In Russ.). DOI:10.33029/0042-8833-2021-90-5-96-103.

Kozlov A.I., Vershubskaya G.G., Lisitsyn D.V., Sanina E.D., Ateeva Y.A. Permskiye i Volzhskiye Finny: Meditsinskaya antropologiya v ekologicheskoy perspektive [Permian and Volga Finns: Medical Anthropology in Ecological Perspective]. Perm, PSPU Publ., 2009. 160 p. (In Russ.).

Maksimenko LV. Epigenetica kak dokazatelnaia baza obraza zisni na zdorovie i bolezni [Epigenetics as an evidence base of the impact of lifestyle on health and disease]. Profilacticheskaya medicina [The Russian Journal of Preventive Medicine], 2019, 22 (2), рр. 115–120. (In Russ.). DOI: 10.17116/profmed201922021115.

 Abondio P., Sazzini M., Garagnani P., Boattini A., Monti D. et al. The genetic variability of APOE in different human populations and its implications for longevity. Genes, 2019, 10 (3), pp. 222. DOI: 10.3390/genes10030222.

Aisyah R., Sadewa A.H., Patria S.Y., Wahab A. The PPARGC1A is the gene responsible for thrifty metabolism related metabolic diseases: a scoping review. Genes, 2022, 13, pp. 1894. DOI: 10.3390/genes13101894.

Ayub Q., Moutsianas L., Chen Y., Panoutsopoulou K., Colonna V. et al. Revisiting the thrifty gene hypothesis via 65 loci associated with susceptibility to type 2 diabetes. Am. J. Hum. Genet., 2014, 94 (2), pp. 176–185.

Barker D. The midwife, the coincidence, and the hypothesis. Br. Med. J., 2003, 327, pp. 1428–1430.

Baschetti R. Diabetes epidemic in newly westernized populations: is it due to thrifty genes or to genetically unknown foods? J. Roy. Soc. Med., 1998, 91 (12), pp. 622–625.

Bernstein M.S., Costanza M.C., James R.W. et al. Physical activity may modulate the effects of APOE genotype on the lipid profile. Arterioscler. Thromb Vasc. Biol., 2002, 22 (1), pp. 133–140.

Bhopal R.S. Genetic explanations 1: the thrifty genotype and its variants. Epidemic of Cardiovascular Disease and Diabetes: Explaining the Phenomenon in South Asians Worldwide. Oxford, 2019; online edn. Oxford Academic, pp. 38–57. DOI: 10.1093/med/9780198833246.003.0002.

Bindon J.R., Baker P.T. Bergmann's rule and the thrifty genotype. Amer. J. Phys. Anthropol., 1997, 104 (2), pp. 201–210.

Borinskaya S.A., Kal'ina N.R., Sanina E.D., Kozhekbaeva ZH.M., Veselovskij E.M. et al. Polymorphism of the apolipoprotein E gene (APOE) in the populations of Russia and neighboring countries. Russ. J. Genet., 2007, 43, pp. 1201–1207. DOI: 10.1134/S1022795407100158.

Cadzow M., Merriman T.R., Boocock J., Dalbeth N., Stamp L.K. et al. Lack of direct evidence for natural selection at the candidate thrifty gene locus, PPARGC1A, BMC Medical Genetics, 2016, 17 (1). pp. 80–93.

Chakravarthy M.V., Booth F.W. Eating, exercise, and “thrifty” genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. Journal of Applied Physiology, 2004, 96, pp. 3–10.

Chermon D., Birk R. FTO common obesity SNPs interact with actionable environmental factors: physical activity, sugar-sweetened beverages and wine consumption. Nutrients, 2022, 14 (19), pp. 4202. DOI: 10.3390/nu14194202.

Corbo R.M, Scacchi R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele? Ann. Hum. Genet., 1999, 63 (4), pp. 301–310.

Egert S., Rimbach G., Huebbe P. ApoE genotype: From geographic distribution to function and responsiveness to dietary factors. Proceedings of the Nutrition Society, 2012, 71 (3), pp. 410–424. DOI:10.1017/S0029665112000249.

Eisenberg D.T., Kuzawa C.W., Hayes M.G. Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history. Am. J. Phys. Anthropol., 2010, 143 (1), pp. 100–111.

Elks C.E., Loos R.J.F., Sharp S.J., Langenberg C., Ring S.M. et al. Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. PLoS Med., 2010, 7 (5), pp. e1000284.

Entringer S., de Punder K., Buss C., Wadhwa P.D. The fetal programming of telomere biology hypothesis: an update. Phil. Trans. R. Soc. B., 2018, 373, pp. 20170151. DOI: 10.1098/rstb.2017.0151.

Genné-Bacon EA. Thinking evolutionarily about obesity. The Yale Journal of Biology and Medicine, 2014, 87 (2), pp. 99–112.

Gicquel C., El-Osta A., Le Bouc Y. Epigenetic regulation and fetal programming. Best Pract. Res. Clin. Endocrinol. Metab., 2008, 22, pp. 1–16.

Gluckman P.D., Hanson M.A. Living with the past: evolution, development, and patterns of disease. Science, 2004, 305, pp. 1733–1736.

Gluckman P.D., Hanson M.A., Beedle A.S. Early life events and their consequences for later disease: a life history and evolutionary perspective. Amer. J. Hum. Biol., 2007, 19, pp. 1–19.

Hales C.N., Barker D.J.P. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia, 1992, 35, pp. 595–601.

Hales C.N., Barker D.J. The thrifty phenotype hypothesis. Br. Med. Bull., 2001, 60, pp. 5–20. DOI: 10.1093/bmb/60.1.5.

Hancock A.M., Clark V.J., Qian Y., Di Rienzo A. Population genetic analysis of the uncoupling proteins supports a role for UCP3 in human cold resistance. Mol. Biol. Evol., 2011, 28 (1), pp. 601–614.

Hanson R.L., Van Hout C.V., Hsueh W.C., Shuldiner A.R., Kobes S. et al. Assessment of the potential role of natural selection in type 2 diabetes and related traits across human continental ancestry groups: comparison of phenotypic with genotypic divergence. Diabetologia, 2020, 63 (12), pp. 2616–2627. DOI: 10.1007/s00125-020-05272-8.

Ho Cha M., Soo Kim K., Suh D., Chung S.I., Yoon Y. A UCP1‐412A> C polymorphism is associated with abdominal fat area in Korean women. Hereditas, 2008, 145 (5), pp. 231–237. DOI: 10.1111/j.1601-5223.2008.02071.x.

Huang C., Chen W., Wang X. Studies on the fat mass and obesity-associated (FTO) gene and its impact on obesity-associated diseases. Genes & Diseases, 2022, DOI: 10.1016/j.gendis.2022.04.014.

Jobling M.A., Hurles M.E., Tyler-Smith C. Human Evolutionary Genetics. NY, Garland Publ., 2004. 523 p. ISSN 2352-3042.

Joffe B., Zimmet P. The thrifty genotype in type 2 diabetes: an unfinished symphony moving to its finale? Endocrine. 1998,9 (2), pp.139–141. DOI: 10.1385/ENDO:9:2:139.

Johnson R.J., Sánchez-Lozada L.G., Nakagawa T., Rodriguez-Iturbe B., Tolan D. et al. Do thrifty genes exist? Revisiting uricase. Obesity, 2022, 30 (10), pp. 1917–1926. DOI: 10.1002/oby.23540.

Koerber-Rosso I., Brandt S., von Schnurbein J., Fischer-Posovszky P., Hoegel J. et al. A fresh look to the phenotype in mono-allelic likely pathogenic variants of the leptin and the leptin receptor gene. Mol. Cell. Pediatr., 2021, 8, p. 10. DOI^ 10.1186/s40348-021-00119-7.

Kozlov A.I., Borinskaya S.A., Sanina E.D. The APOE gene ε4/ε4 “thrifty genotype” and risk of metabolic disorders in populations of the Ural region. Russian Journal of Genetics: Applied Research, 2012, 2 (2), pp.135–140.

Kozlov A., Vershubsky G., Borinskaya S., Sokolova M., Nuvano V. Activity of disaccharidases in Arctic populations: Evolutionary aspects. J. Physiol. Anthropol., 2005, 24, pp. 473–476.

Li E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet., 2002, 3, pp. 662–673.

Li X., Sun X., Jin L., Xue F. Worldwide spatial genetic structure of angiotensin-converting enzyme gene: a new evolutionary ecological evidence for the thrifty genotype hypothesis. Eur. J. Hum. Genet., 2011, 19 (9), pp. 1002–1008. DOI: 10.1038/ejhg.2011.66.

McDermott R. Ethics, epidemiology and the thrifty gene: biological determinism as a health hazard. Soc. Sci. Med., 1998, 47 (9). pp. 1189–1195.

Meeks K.A.C., Bentley A.R., Adeyemo A.A., Rotimi C.N. Evolutionary forces in diabetes and hypertension pathogenesis in Africans. Hum. Mol. Genet., 2021, 30, pp. R110–R118.

Meeks K.A.C., Henneman P., Venema A., Addo J., Bahendeka S. et al. Epigenome-wide association study in whole blood on type 2 diabetes among sub-Saharan African individuals: findings from the RODAM study. Int. J. Epidemiol., 2019, 48, pp. 58–70.

Moleres A., Rendo-Urteaga T., Zulet M.A., Marcos A., Campoy C. et al. Obesity susceptibility loci on body mass index and weight loss in Spanish adolescents after a lifestyle intervention. J. Pediatr., 2012, 161 (3), pp. 466–470.

Neel J.V. Diabetes mellitus: A "thrifty" genotype rendered detrimental by "progress"? Am. J. Hum. Genet., 1962, 14 (4), pp.353–362.

Neel J.V. The "Thrifty Genotype" in 1998. Nutr. Rev., 1999, 57 (5, Pt II), pp. 2–9.

Nishimura T., Katsumura T., Motoi M., Oota H., Watanuki S. Experimental evidence reveals the UCP1 genotype changes the oxygen consumption attributed to non-shivering thermogenesis in humans. Sci. Rep., 2017, 7 (1). pp. 1–7. DOI: 10.1038/s41598-017-05766-3

Odling-Smee F.J., Laland K.N., Feldman M.W. Niche Construction: The Neglected Process in Evolution. Princeton: Princeton University Press, 2003, pp. 488

Prentice A.M. Starvation in humans: evolutionary background and contemporary implications. Mech Ageing Dev., 2005, 126 (9), pp. 976–981.

Raghavan M., Steinrücken M., Harris K., Schiffels S., Rasmussen S. et al. Genomic evidence for the Pleistocene and recent population history of Native Americans. Science, 2015, 349 (6250). pp. aab3884. DOI: 10.1126/science.aab3884

Reddon H., Patel Y., Turcotte M., Pigeyre M., Meyre D. Revisiting the evolutionary origins of obesity: lazy versus peppy-thrifty genotype hypothesis. Int. J. Obes., 2018, 19 (11), pp. 1525–1543. DOI: 10.1111/obr.12742.

Rosenquist J.N., Lehrer S.F., Malley A.J., Zaslavsky A.M., Smoller J.W., et al. Cohort of birth modifies the association between FTO genotype and BMI. Proc. Natl. Acad. Sci. USA, 2015, 112 (2). pp. 354–359. DOI: 10.1073/pnas.1411893111

Sellayah D. The impact of early human migration on brown adipose tissue evolution and its relevance to the modern obesity pandemic. J. Endocrine Soc., 2019, 3 (2), pp. 372–386. DOI: 10.1210/js.2018-00363.

Sellayah D., Cagampang F., Cox R. On the evolutionary origins of obesity: a new hypothesis. Endocrinology, 2014, 155 (5), pp. 1573–1588. DOI:10.1210/en.2013-2103.

Sharma A.M. The thrifty-genotype hypothesis and its implications for the study of complex genetic disorders in man. J. Mol. Med., 1998, 76 (8), pp. 568–571.

Shinozaki K., Okuda M., Hinoda Y., Okayama N., Fukuda T., et al. Fat-mass and obesity-associated gene variant and changes of body mass index from ages 3 to 13 years. I. Pract., 2014, 8 (4), pp. 382–387. DOI: 10.1016/j.orcp.2013.07.005.

Southam L., Soranzo N., Montgomery S.B., Frayling T.M., McCarthy M.I. et al. Is the thrifty genotype hypothesis supported by evidence based on confirmed type 2 diabetes- and obesity-susceptibility variants? Diabetologia, 2009, 52 (9), pp. 1846–1851. DOI: 10.1007/s00125-009-1419-3.

Speakman J.R. Thrifty genes for obesity and the metabolic syndrome – time to call off the search? Diab. Vasc. Dis. Res., 2006, 3 (1), pp. 7–11.

Speakman J. Thrifty genes for obesity, an attractive but flawed idea, and an alternative perspective: the ‘drifty gene’ hypothesis. Int. J. Obes., 2008, 32, pp. 1611–1617. DOI: 10.1038/ijo.2008.161.

Tanaka R., Fuse S., Kuroiwa M., Amagasa S., Endo T. et al. Vigorous-intensity physical activities are associated with high brown adipose tissue density in humans. Intern. J. Envirl. Res. Publ. Health, 2020, 17 (8), pp. 2796. DOI: 10.3390/ijerph17082796.

Wang G., Speakman J.R. Analysis of positive selection at single nucleotide polymorphisms associated with body mass index does not support the "thrifty gene" hypothesis. Cell Metabolism, 2016, 24 (4), pp. 531–541. DOI: 10.1016/j.cmet.2016.08.014.

Watanabe M., Risi R., Tafuri M.A., Silvestri V., D’Andrea D. et al. Bone density and genomic analysis unfold cold adaptation mechanisms of ancient inhabitants of Tierra del Fuego. Sci. Rep., 2021, 11 (1), pp. 23290. DOI: 10.1038/s41598-021-02783-1.

Wu T., Xu S. Understanding the contemporary high obesity rate from an evolutionary genetic perspective. Hereditas, 2023, 160, p. 5. DOI: 10.1186/s41065-023-00268-x.

Zhang Z., Chen N., Liu R., Yin N., He Y. et al. The rs1421085 variant within FTO promotes but not inhibits thermogenesis and is potentially associated with human migration. BioRxiv. 2021, pp. 456245. DOI: 10.1101/2021.08.13.456245.