Nunavik Inuit's Genetic Distinctiveness Analysis PDF

Nunavik Inuit’s Are they becoming genetically distinct? Anna Derrick [email protected]  Quiz Test your knowledge from last lecture! (BRCA gene mutat...

Nunavik Inuit’s Are they becoming genetically distinct? Anna Derrick [email protected]  Quiz Test your knowledge from last lecture! (BRCA gene mutations) https://kahoot.it Also available on: Learning Outcomes Understand the evolutionary processes contributing to the Canadian Inuits becoming genetically distinct. Outline the physiological and genetic adaptations of the Canadian Inuits.  Who are the Inuit population? Inuit population inhabit Artic regions of Canada, Alaska, Greenland. One of the three major groups of indigenous people living in Canada. Legally recognized in the Constitution Act of 1982 - Inuit, First Nations and Metis. Term ‘Eskimo’ considered offensive. Where did the Inuit population originate? They are descendants from ‘Thule People’, Thule people originally from Siberia. Inhabited western Alaska by 1,000CE. Migrated east across northern Canada, reaching Greenland by 1,200CE. Replaced Dorset population that previously inhabited the regions. Inuits colonised the region fully by 1,400CE.  Where do the Inuit population live? Nunavik Nunavut Inuvialuit Settlement Nunatsiavut Region Nanangat area  Nunavik Inuit Climate The Inuit population have Temperature accomplished something that no Months Normal Warmest Coldest other community have managed. January -23.5°C -19.0°C -28.2°C February -23.1°C -18.2°C -28.1°C To independently survive in the March -18.5°C -13.2°C -23.9°C high Artic without supplies of food, April -9.4°C -4.4°C -14.5°C technology and fuel from more May -0.1°C 3.9°C -4.1°C June 6.8°C 11.9°C 1.6°C temperate climates. July 11.0°C 16.6°C 5.4°C August 10.4°C 15.3°C 5.4°C September 5.3°C 9.2°C 1.5°C October -0.8°C 2.0°C -3.8°C November -8.3°C -4.7°C -12.0°C December -19.1°C -14.9°C -23.3°C Physiological adaptions for climate. Stocky body and shorter limbs create smaller "body surface-area-to-volume ratio" prevent excessive heat loss in cold climate. Larger eyes and brain (visual cortex) to improve visual ability at low light intensity present at high latitudes. Nunavik Inuit Food Sources Fatty meats of wild animals, such as polar bears, artic hares, sealions, whales and fish. Consume many parts of the animals including the meat, bone marrow, brains and organs. As well as seaweeds and wild berries.  Nunavik Inuit Food Sources Traditional diet: 50% fats - monounsaturated fats and omega-3 fatty acids. 40% - protein from animals. Almost no nutrition is consumed as carbohydrates. Have physiological adaptions for the metabolism of this diet reduced risk of cardiovascular disease and diabetes. https://www.youtube.com/watch?v=Dc3_LLXsguw  Physiological adaptations for high fat diet High rates of gluconeogenesis - the process in which glucose is produced in the body from non carbohydrate sources. Lactate, Pyruvate and Glutamate from fatty foods and protein diets feeds into the TCA cycle. The liver is one of the main sites, along with the kidneys, for gluconeogenesis to occur this is supported by a larger liver size. Physiological adaptations for high fat diet Reduced levels of low-density lipioprotein (LDL) ‘bad’ cholesterol regardless of high fat diet. LDL transports lipids and cholesterol to the cells via the arteries. Too much cholesterol and lipids leads to atherosclerosis, a build up of plaque within the arteries. Increased risk of blood clots leading to a heart attack or a stroke. Plaque build up can also reduce blood flow and oxygen to major organs. Physiological adaptations for high fat diet Lower fasting insulin levels - contributes to the reduced risk of heart disease, kidney disease, diabetes and cancer. Insulin is the hormone that your body uses to control blood glucose. Insulin also a key factor in hyperplasia - the growth of tissue, so high levels of fasting insulin can lead to increase cell growth and hence possibly cancer development. The Nunavik Inuit population have a reduced risk of cancers such as prostate and colorectal.  Genetic architecture of Nunavik Inuit A study by Zhou. S., et al. (2019) performed WES on 170 Nunavik Inuit individuals. Genetic background of Nunavik Inuit to be distinct from any known present-day population. Little evidence of gene flow from European or present-day Native American peoples. Zhou. S., et al. (2019). Genetic architecture and adaptations of Nunavik Inuit. PNAS. 116(32), 16012–16017.  Gene variants under Natural Selection Compared the frequency of 387,339 single nucleotide variants found in coding regions between Nunavik Inuit and Han Chinese population with European ancestry population as an outgroup. Show allele frequency differences particularly in genes whose pathways involving fatty acid metabolism and cellular adhesion. Zhou. S., et al. (2019). Genetic architecture and adaptations of Nunavik Inuit. PNAS. 116(32), 16012–16017.  CPT1A The variant with the highest score validated previous findings: A genotyping study took 113 Nunavik Inuit individuals from 13 inhabited villages of Nunavik, and compared variant frequency against HapMap genotype data from Asian (CHB and JPT), European (CEU) and African (YRI) populations. CPT1A NP_001867.2: p.Pro479Leu (rs80356779) is an Inuit specific variant. The variant is present in almost all the described population - ‘Fixation’. Zhou. S., et al. (2015). Increased Missense Mutation Burden of Fatty Acid Metabolism Related Genes in Nunavik Inuit Population. PLOS0. 10(5) CPT1A CPT1A is located on chromosome 11q13.3. Encodes the Carnitine Palmitoyltransferase 1A (CPT1) enzyme. CPT1, is predominantly expressed in the liver. Essential for fatty acid oxidation, a multistep process that metabolises fats and converts them into energy.  FADS1 Previously reported selection in the Greenlandic Inuit population. (Fumagalli. M., et al., 2015) Allele-frequency difference between Nunavik Inuit and other populations within the MYRF-FADS1-3 cluster (chr11: 61.5–61.6 Mb), highest in FADS1. FADS1 is located on chromosome 11q12.2. Encodes the fatty acid desaturase 1 enzyme which is involved in both the omega-3 and omega-6 biosynthesis pathways. Probably under selection, driven by a diet high in omega-3 polyunsaturated fatty acids (PUFAs).  CPNE7 An alternatively splicing variant in CPNE7 (NP_705900.1:p.Gly445Gly, rs12445560) Extremely high allele frequency in the Nunavik Inuit population (95%), compared to Northeast Siberians (40%), Native Americans (74%), Europeans and East Asians (1%) and much rarer in Africans (0.1%). Zhou. S., et al. (2019). Genetic architecture and adaptations of Nunavik Inuit. PNAS. 116(32), 16012–16017.  CPNE7 CPNE7 is located on chromosome 16q24.3. Encodes a member of the Copine protein family. Calcium dependant phospholipids binding proteins and also belongs to the von Willebrand factor A domain-containing proteins - important in cell adhesion and migration events. Copines are associated with coronary artery disease and obesity indicating they also function in lipid metabolism pathways. Zhou. S., et al. (2019). Genetic architecture and adaptations of Nunavik Inuit. PNAS. 116(32), 16012–16017.  ICAM5 Two missense single nucleotide variants seen at a ‘near- fixation ‘ level (98%) within the Nunavik Inuit population. ICAM5 is located on chromosome 19p13.2 and Encodes a neuronal-specific intercellular adhesion protein a Type 1 transmembrane glycoproteins. Critical component in normal brain development. ICAMs known to be involved in fatty acid metabolism, oxidative stress and inflammatory response. What evolutionary processes have contributed to the Nunavik Inuit becoming genetically distinct? 1. Population Migration (NO Gene flow) - The Founder effect 2. Barriers to movement 3. Natural Selection - Adaption to local environmental conditions  Population Migration - Founder Effect The Thule population moved (migrated) to another geographical area from Siberia, to Alaska, through to Canada and Greenland. mtDNA study shows no evidence of genetic mixing with the pre-existing Dorset population. Gene flow/gene migration did NOT occur. More typical of the Founder effect Barriers to movement Nearly no ancestry from other present-day populations. Distinct from other Arctic indigenous population. Adaption to local environmental conditions Some individuals in a population may possess genetic combinations that are valuable for survival in the local environment. These individuals find the environment less hostile. The individuals in the population with unfavourable genetic combinations leave the population more often, either by death or migration. Removing their genetic combinations from the population - SURVIVAL OF THE FITTEST Local populations that occupy sites that differ greatly from conditions at other locations would be expected to consist of individuals having gene combinations suited to local conditions – MICROEVOLUTION. That the end of todays lecture…. Thank you and don’t forget to look over the content for the quiz next time!