Genetic Geography and Population Structure Oscar Lao - PowerPoint PPT Presentation

Genetic Geography and Population Structure Oscar Lao oscar.lao@cnag.crg.eu 15.11.2018

GENETIC SIMILARITY IN HUMANS “All our social policies are based on the fact that their intelligence is the same as ours — whereas all the testing says not really,” HUMANS MANS (FROM A GENETIC POINT OF VI VIEW) HUMANS ANS GENETICALL CALLY Y Some me scientists entists SIMILAR AR

GUESS THE GENETIC ANCESTRY a) b) d) c)

GUESS THE GENETIC ANCESTRY ( and be wrong !) a) b) d) c)

GUESS THE GENETIC ANCESTRY EUROPEAN ANCESTRY

GUESS THE GENETIC ANCESTRY ( if you dare !) Erased recent historical Tiger Woods calls himself memory & Forensics "Cablinasian “ • Colonization of Americas & slavery • Romani Diaspora • Australian’s Stolen Children • Recent migrations • Bombing attacks • … Ca ucasian, Bl ack, American In dian, Asian

TOPICS TO BE DISCUSSED • Why is there population substructure? • How much population substructure in the human genome? (Do races exist?) • Some examples of population substructure • Final conclusions & suggestions

WHY IS THERE POPULATION SUBSTRUCTURE

METASOURCES OF GENETIC VARIATION Evolutionary parameters Population Sample Stochastic Stochastic “Demographic” Evolutionary Sampling processes process process Mutation ATGCATGGGCTATTGGACCT ATG G ATGGGCTATTG C ACCT Recombination ATGCATGGGC A ATTG C ACCT ATGCATGGGC A ATTGGACCT ATG G ATGGGCTATTG C ACCT Selection Genetic drift Migration/Isolation Inference

DEMOGRAPHY & POPULATION HISTORY Van Oven and Lao International Encyclopedia of Social and Behavioral Sciences 2nd Edition • Physical factors • Distance • Barriers • … • Cultural factors • Language • Religion • …

DEMOGRAPHY & POPULATION HISTORY Nielsen et al 2017, Nature

DEMOGRAPHY & POPULATION HISTORY Scientific American 308, 66 - 71 (2013)

DEMOGRAPHY & POPULATION HISTORY Dolgova and Lao ; Genes 2018, 9(7), 358; https://doi.org/10.3390/genes9070358

DEMOGRAPHY & POPULATION HISTORY Lorente-Galdos *, Lao * et al under review in Genome Biology Mondal, Bertranpetit* and Lao* , accepted for publication in Nature Communications

DEMOGRAPHY & POPULATION HISTORY Curr Biol. 2016;26(9):1241-7 Science. 2016 Feb 12;351(6274):737-41

METASOURCES OF GENETIC VARIATION Evolutionary parameters Population Sample Stochastic Stochastic “Selective” processes Evolutionary Sampling process process Mutation ATGCATGGGCTATTGGACCT ATG G ATGGGCTATTG C ACCT Recombination ATGCATGGGC A ATTG C ACCT ATGCATGGGC A ATTGGACCT ATG G ATGGGCTATTG C ACCT Selection Genetic drift Migration/Isolation Inference

SELECTION CULTURAL ADAPTATION IS THE MAIN FORCE OF OUR SUCCESS https://es.pinterest.com/ http://www.bbc.co.uk/bitesize/ks3/history/industrial_era/the_industrial_revolution/revision/2/

SELECTION Fan et al 2016

SELECTION LCT • Humans are mammals • We consume milk when we are babies • This is done thanks to the enzyme LACTASE ( LCT ) • Milk is a complete source of energy and proteins + defense

SELECTION LCT • The capacity to metabolize lactose disappears at adult age in almost all the mammal species • LCT gene is not expressed anymore because there is no more maternal milk to drink • Or is it not?

SELECTION LCT • How to recognize if you are lactose intolerant ? – Can be asymptomatic – Gas production – Diarrhea – Related to diseases such as inflammatory bowel disease – Usually lactose intolerant people “don’t like milk”

SELECTION LCT

SELECTION LCT Yang et al (2012) Nature Genetics

SELECTION LCT

EVOLUTIONARY MEDICINE: USING EVOLUTION TO UNDERSTAND HUMAN DISEASE

EVOLUTIONARY MEDICINE: USING EVOLUTION TO UNDERSTAND HUMAN DISEASE Conditions thought to be caused by mismatch Acid reflux/chronic heartburn Depression Inflammatory bowel disease Acne Diabetes (type 1) Lactose intolerance Alzheimer’s disease Diaper rash Lower back pain Anxiety Eating disorders Malocclusion Apnea Emphysema Metabolic syndrome Asthma Endometriosis Multiple sclerosis Athlete’s foot Fatty liver syndrome Myopia Attention deficit hyperactivity disorder Fibromyalgia Obsessive-compulsive disorder Bunions Flat feet Osteoporosis Cancers (only certain ones) Glaucoma Plantar fascitis Carpal tunnel syndrome Gout Polycystic ovarian syndrome Cavities Hammer toes Pre-eclampsia Chronic fatigue syndrome Hemorrhoids Rickets Cirrhosis High blood pressure (hypertension) Scurvy Constipation (chronic) Iodine deficiency (goiter/cretinism) Stomach ulcers Coronary heart disease Impacted wisdom teeth Crohn’s disease Imsomnia (chronic)

2) DO RACES EXIST?

FACTS: TOO MANY CLASSIFICATIONS Barbujani, Current Genomics Table 1. Lists of Human Races No. of races Races proposed Author Races proposed Linnaeus (1735) 6 Europaeus, Asiaticus, Afer, Americanus, Ferus, Monstruosus Buffon (1749) 6 Laplander, Tartar, South Asian, European, Ethiopian, American Blumenbach (1795) 5 Caucasian, Mongolian, Ethiopian, American, Malay Cuvier (1828) 3 Caucasoid, Negroid, Mongoloid Deniker (1900) 29 Weinert (1935) 17 Von Eickstedt (1937) 38 Biasutti (1959) 53 Coon (1962) 5 Congoid, Capoid, Caucasoid, Mongoloid, Australoid US Office of Management and 5 African-American, White, American Budget (1997) Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander Risch et al. (2002) Fig. 1 5 African, Caucasian, Pacific islanders, East Asian, Native American Risch et al. (2002) Table 3 5 African Americans, Caucasians, Hispanic Americans, East Asians, Native Americans

FACTS: NOT TOO MUCH VARIATION http://theadvancedapes.com/genetic-origins/

FACTS: NOT TOO MUCH VARIATION Pagani et al, 2016, Nature Mallick et al, 2016, Nature De Manuel et al, 2016 Science

FACTS: NOT TOO MUCH VARIATION AMONG POPULATIONS Classifying individuals according to continental origin is not a good idea Richard Lewontin Lewontin, R "The Apportionment of Human Diversity," Evolutionary Biology, vol. 6 (1972) pp. 391-398

FACTS: GENETIC VARIATION FOLLOWS A GRADIENT Using data from G3 (Bethesda). 2013 May 20;3(5):891-907

FACTS: GENETIC VARIATION FOLLOWS A GRADIENT Henn 2015 Using data from G3 (Bethesda). 2013 May 20;3(5):891-907 Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15942-7

3) SOME EXAMPLES

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE Lao et al 2007 Current Biology Yang et al (2012) Nature Genetics Novembre et al 2007 Nature

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE Maceda-Porto* , Martin-Alvarez*, et al, Lao** and Moral**, in preparation NGS 30 individuals at 30x

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE Maceda-Porto* , Martin-Alvarez*, et al, Lao** and Moral**, in preparation Number of highly damaging variants

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE Mendizabal and Lao et al, Current Biology 2012

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE Mendizabal and Lao et al, Current Biology 2012 Philip IV of Spain , who declared that Romani did not exist (they are Spanish people who had made up an artificial language)

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE Mendizabal and Lao et al, Current Biology 2012

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE Mendizabal and Lao et al, Current Biology 2012

EXAMPLE II:POPULATION SUBSTRUCTURE IN ABORIGINAL AUSTRALIA Sapfo-Malaspina et al, 2016 Nature

EXAMPLE II:POPULATION SUBSTRUCTURE IN ABORIGINAL AUSTRALIA Sapfo-Malaspina et al, 2016 Nature

EXAMPLE II:POPULATION SUBSTRUCTURE IN ABORIGINAL AUSTRALIA Sapfo-Malaspina et al, 2016 Nature 40 mean(generations since first contact) ” Australian ” 30 ”Europe” ”East Asian ” ENY ” Papuan ” RIV NGA 20 PIL WPA BDV CAI 10 WON WCD 80 100 120 140 160 180 time since first contact with Europeans

CONCLUSIONS

FINAL REMARKS • Population substructure must be interpreted in evolutionary terms – Demographic – Selective • The amount of population substructure depends on the genomic region we are considering – Magnitude – Geographic distribution • The amount of population substructure we detect depends on the assumptions we make

FINAL REMARKS • The amount of population substructure must be interpreted in the context of what we are studying • AVOID over-interpretation

FINAL REMARKS A “ small ” or “ modest ” amount of genetic diversity when compared with other species can be “ big ” when trying to detect extremely small effects

Thank you very much! oscar.lao@cnag.crg.eu