Class 17 - Oct 22 - IB35ac Class 17: Thrifty genotypes,...

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Unformatted text preview: IB35ac Class 17: Thrifty genotypes, natural selection Today we'll talk about body fat and hypertension and the interplay between our past environments and the westernized one we find ourselves in today. IB35 Human Biological Variation Class #17 Importance of Evolutionary History Different forces of natural selection Convergence/Parallelism Drift Sexual selection Light skin color of neanderthals Thrifty Genotypes? Obesity and Hypertension Topics for today: The acquisition of the same biological trait in unrelated lineages The change in the relative frequency with which an allele appears in a population due to random sampling and chance What people look like Skin color Hair Eyes Body shape Body fat By 2007, 60million adults in America are obese Measuring Body Fat Hydrodensitometry (underwater weighing) Measures whole body density by determining body volume BMI: The Body Mass Index Calipers ( p (anthropometry skinfold p y measurements) DEXA (dual energy x-ray absorptiometry) Whole body scanner that has two low dose xrays at different sources that read bone and soft tissue mass simultaneously 1 Not as accurate - Fit people with more muscle mass may appear to have higher BMI BMI: The Body Mass Index BMI Categories Underweight < 18.5 Normal weight = 18.5 24.6 Overweight = 25 29.9 Obesity > 30 Restricted Calorie Diets 5'2" 100lbs BMI = 18.3 5'2" 120lbs BMI = 21.9 5'2" 140lbs BMI = 25.6 58 5'8" 120lbs BMI = 18 2 18.2 5'8" 150lbs BMI = 22.8 5'8" 180lbs BMI = 27.4 6'2" 140lbs BMI = 18.0 6'2" 150lbs BMI = 19.3 6'2" 200lbs BMI = 25.7 Canto Owen (at ~ 26 years of age) Ate 25% more calories than Owen Better health indicators than Owen The Health Risks of Obesity Heart disease and stroke High blood pressure Diabetes Cancer Gallbladder disease and gallstones Osteoarthritis Gout Breathing problems, such as sleep apnea (when a person stops breathing for a short time during sleep) and asthma The Health Risks of Obesity Table 1. Prevalence of Medical Conditions by Body Mass Index (BMI) for Men Body Mass Index Medical Condition 18.5 to 24.9 25 to 29.9 30 to 34.9 > 40 Prevalence Ratio (%) Type 2 Diabetes Coronary Heart Disease High Blood Pressure Osteoarthritis 2.03 8.84 23.47 2.59 4.93 9.60 34.16 4.55 4.66 10.10 16.01 48.95 10.65 13.97 64.53 10.04 Source: NHANES III, 1988 - 1994. , Table 2. Prevalence of Medical Conditions by Body Mass Index (BMI) for Women Body Mass Index Medical Condition 18.5 to 24.9 25 to 29.9 30 to 34.9 > 40 Prevalence Ratio (%) Type 2 Diabetes Coronary Heart Disease High Blood Pressure Osteoarthritis 2.38 6.87 23.26 5.22 7.12 11.13 38.77 8.51 9.94 7.24 12.56 47.95 19.89 19.22 63.16 17.19 Source: NHANES III, 1988 - 1994. From: Men and women display similar trends with increasing body fat: health risks increases Environmental Influence Environmental factors are very important on the development of insulin resistance and diabetes in all populations of the world. Rural Japan 4% Rural S. Korea 2-4% Africans 1% Mexican Pima 6-11% Japanese-Americans 21% Seoul 13-16% African-Americans 12% Arizona Pima 37-54% Types of Genetic Affects Monogenic Dominant Codominant Recessive Ears, Lactase Persistence Blood Type Albinism, Hemophilia Eye Color Oligogenic Complex Traits From rural to urban environments, diabetes occurrence increases ->Greater increase in diabetes rate ->Possible predisposition to Type II Diabetes Polygenic Age affects Gene-by-environment interaction Gene-by-sex interaction Environment-by-sex interaction Complex traits - Multiple factors are affecting phenotypes E.g. Height Straight/Curly hair is incomplete dominance 2 Evolution of the Human Lifestyle & Diet Similar to hunter-gatherers And then the Neolithic Consequences of the Neolithic Transition was accompanied by major changes in diet for most human populations Traits that were previously beneficial became harmful in the changed nutritional environment Agricultural Lifestyle Homogenous Diets (Same types of food) TYPE I Diabetes - Not enough Insulin TYPE II Diabetes - Non-insulin Dependent Diabetes Mellitus - Adult onset Diabetes Evolutionary Hypothesis Pandemic of obesity is caused by a profound mismatch between humanity's present environmental circumstances and those that have molded evolutionary selection The "Thrifty" Genotype 1962, James Neel Noninsulin dependent diabetes mellitus is the result of a thrifty genotype rendered detrimental by cultural change Metabolic efficiency in storage of excess calories is achieved through over-secretion of insulin which increases fat tissue formation and the accumulation of an energy store. t Rapid release of the hormone insulin in response to elevated blood-sugar levels (hyperglycemia) was advantageous to our ancestors, allowing them to build up fat deposits in times of plenty In an environment where there is overabundant food, this rapid response is detrimental overproduction of insulin leads to insulin resistance, subsequent high levels of blood glucose, and the set of debilitating symptoms constituting diabetes ->Over-secretion of insulin, can store calories for later ->Over-abundance of food, makes over-secretion of insulin not useful, resulting in insulin resistance Example: Oceanic Populations Example: Oceanic Populations Bindon JR, and Baker PT. 1997. Am J Phys Anthropol 104:201-210. Bindon JR, and Baker PT. 1997. Am J Phys Anthropol 104:201-210. ->In order to populate the outer islands, people needed to be more hardy ->Thrifty genotype selected for Neuru ->High obesity levels ->High incidence of health risks Higher Prevalence of Thrifty Genotype ->Native Americans ->Migration into the Americas: crossing the Bering Strait 3 Chemical compound, foreign to the body, that can disrupt normal development or homeostasis leading to obesity The "thrifty" phenotype The fetus adapts to maternal malnutrition by itself becoming nutritionally thrifty, resulting in decreased growth, hormonal and metabolic adaptations, and altered growth and function in the cells of the pancreas responsible for insulin secretion Over-nutrition later in life makes this developmental adaptation disadvantageous, as it predisposes to NIDDM through reduced secretion of insulin or insulin resistance A provocative new hypothesis: Obesity in infants has risen by 73% since 1980 Hormome-mimicking pollutants Turn more precursor cells into fat cells in the developing fetus Alter metabolic rate so body hoards calories For example: bisphenol A (used in plastic) in culture, this chemical caused some cells to turn into fat cells, and caused fat cells to proliferate Obesogens Used to make baby bottles Phenotype VS Genotype Maternal Environment VS Underlying Genetic Predispositions Systole - Contraction of Heart Diastole - Relaxation of Heart Pressure on arteries as blood flows through The Historical Importance of Salt Human history Animals and salt licks Chimpanzees Hypertension and Salt Salt deposit that animals regularly lick ->Production of salt 3000ya in Egypt ->Used for trade, tanning Hypertension and Salt There is a high prevalence of hypertension (high blood pressure) among African-Americans Their ancestors had a low-salt diet and were prone to losing salt through sweat in a hot climate "Thrifty" adaptation = increased sodium retention 825T allele of the GNB3 gene Associated with hypertension 60-80% allele frequency in sub-Saharan Africans, African-Americans, and Australian Aborigines 40-60% in East Asians 30% in Europeans The BiDil Controversy Europeans selected for resistance to salt in diet ->Originally rejected in '95 but approved in 2005 ->Self-identified African-Americans seem to have a higher survival rate than white patients ->Negative reaction by Black community ->Results suggest underlying genetic differences between races and the concept of race is real ->Undermines underlying socio-economic factors that have an impact on health ->Pharmecogenomics 4 An organism has to acquire a certain amount of polygenes for a trait in order to produce a sufficient amount of a particular chemical to overcome a threshold Applying this to Medical Research Disease as a threshold effect Studying the Extremes of the Distribution Two Approaches Association studies Family-based studies ->Different Populations and how they respond to it ->Find association of higher/lower frequency of something in comparison to other populations Diseases are found in the extremes ->Avoid the potential confounding effects of population stratification by using the parents as controls for the case, which is their affected offspring Heritability (h2) The proportion of the variance that can be attributed to genetic effects Decomposing the Phenotypic Variance Continuously varying trait v TOTAL = v GENES + v ENVIRONMENT Pedigree / Family Tree Baboons ->Family-based studies Quantitative Genetics Phenotypic variance 2 2 p = g + e2 2 G h = 2 P 2 Heritability 5 Southwest Foundation for Biomedical Research Captive Baboons SFBR not yet published Diet-genotype study Alaskan Eskimos Voruganti et al., 2006 A powerful tool to use in conjunction with controlled studies... ->Some Baboons fed high-protein diet ->Some Baboons fed high-fat diet ->Measured ->High density lipoproteins ->Low density lipoproteins (Bad) ->Genes determined by what you're eating High correlation between BMI and low density lipoproteins Conclusions An evolutionary perspective can explain why some common genotypes may exist despite seeming maladaptive, and why they may be found at higher frequencies in some populations Complex traits are influence by multiple genes and multiple environmental affects, but by studying people and populations at the extremes of the distribution we can start to disentangle these factors 6 ...
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