Genetic Geography and Population Structure Oscar Lao - PowerPoint PPT Presentation

Genetic Geography and Population Structure Oscar Lao oscar.lao@cnag.crg.eu 16.11.2017

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,” HUMA UMANS (FRO FROM A GE GENETIC POI OINT OF OF VI VIEW) HUMANS HUM GENE NETI TICALLY Y Som ome sc scie ientists SIMI SI MILAR

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

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

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?) • How to detect population substructure? Available methods & caveats • Some examples of population substructure • Final conclusions & suggestions

1) 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

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

METASOURCES OF GENETIC VARIATION DEMOGRAPHY & POPULATION HISTORY Nature Reviews Genetics 13, 745-753 (October 2012)

METASOURCES OF GENETIC VARIATION DEMOGRAPHY & POPULATION HISTORY Green et al. 2010 Reich et al. 2010 ~5% of Melanesian genome derive from Denisovans ~2.5% of non-African genomes derive from Neanderthals

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

METASOURCES OF GENETIC VARIATION SELECTION • Adaptation to new environments • Food production – new diets • Population increase – new diseases

HUMAN CULTURAL EVOLUTION https://es.pinterest.com/

METASOURCES OF GENETIC VARIATION SELECTION Fan et al 2016

METASOURCES OF GENETIC VARIATION SELECTION IN 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

METASOURCES OF GENETIC VARIATION SELECTION IN 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?

METASOURCES OF GENETIC VARIATION SELECTION IN 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”

METASOURCES OF GENETIC VARIATION SELECTION IN LCT

METASOURCES OF GENETIC VARIATION SELECTION IN LCT Yang et al (2012) Nature Genetics

METASOURCES OF GENETIC VARIATION SELECTION IN LCT

CONSEQUENCES OF HUMAN EVOLUTION EVOLUTIONARY MISMATCH

CONSEQUENCES OF HUMAN EVOLUTION EVOLUTIONARY MISMATCH Stearns and Medzhitov, 2016

EVOLUTIONARY MISMATCH ADHD  Impairing disease & Fitness Faraone, et al ., 2015. Nat. Rev. Dis. Primers

EVOLUTIONARY MISMATCH ADHD  High energy  S pon tane ity PREVALENCE ~2.5% R is k - t a k i n g  SYMPTOMS IMPAIRING HERETABILITY (76%) I n n o v a t i o n   C r e a t i v i t y  … ADHD… AN EVOLUTIONARY MISMATCH? CURRENT ENVIRONMENT Theories: Low motor activity PROBLEM-SOLVING Hunter-farmer theory  Non-impulsive Response-readiness theory  Wader theory  Focused attention Hipervigilant Fighter theory  Impulsive PAST ENVIRONMENT High motor activity RESPONSE-READY Adapted from Jensen et al. , 1997. JAACAP

EVOLUTIONARY MISMATCH ADHD Fu et al ., 2016 dataset Lazaridis et al. , 2016 dataset (initially 51 genomes) (initially 281 genomes) Demontis et al. , 2017

EVOLUTIONARY MISMATCH ADHD LAZARIDIS dataset FU dataset (robust regression) R = -0.26 R = -0.44   P value = 1.37·10 -3 P value = 0.04   P value neutrality = 3·10 -4   P value neutrality = 0.019  ADHD risk alleles in ancient samples seem to be have been negatively shaped by selection. Esteller et al, in preparation

EVOLUTIONARY MISMATCH ADHD SDS statistic (Field et al. , 2016. Science ) Spearman correlation: (risk allele ADHD) ρ observed = 0.198 Pvalue association SDS ADHD P value = 0.0217  There is evidence of recent polygenic adaptation in the alleles that are protective for ADHD at a genomic level. Esteller et al, in preparation

2) DO RACES EXIST?

FACTS: TOO MANY CLASSIFICATIONS 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 Barbujani, Current Genomics

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

FACTS: GENETIC VARIATION FOLLOWS A GRADIENT Jay et al, 2012 MBE

FACTS: GENETIC VARIATION FOLLOWS A GRADIENT Maceda and Lao, in preparation

3) HOW TO DETECT POPULATION SUBSTRUCTURE?

METHODS FOR INFERRING POPULATION SUBSTRUCTURE K = 4 α 4 α 2 α 1 α 3 Dim 2 snp snp snp snp snp snp … snp 1 2 3 4 5 6 n I 1 0 1 2 1 0 0 1 I 2 0 0 2 0 0 2 1 I 3 1 1 2 0 0 2 0 I 4 0 1 2 0 1 2 0 Dim 1 I 5 1 1 2 0 1 2 1 … I m 2 0 1 0 1 2 2 AA = 0 AB = 1 Algorithmic ancestry estimation Model-based ancestry estimation BB = 2 Van Oven and Lao International Encyclopedia of Social and Behavioral Sciences 2nd Edition

METHODS FOR INFERRING POPULATION SUBSTRUCTURE snp snp snp snp snp snp … snp 1 2 3 4 5 6 n I 1 0 1 2 1 0 0 1 I 2 0 0 2 0 0 2 1 I 3 1 1 2 0 0 2 0 I 4 0 1 2 0 1 2 0 I 5 1 1 2 0 1 2 1 … I m 2 0 1 0 1 2 2 AA = 0 AB = 1 Spatial ancestry estimation BB = 2 Wollstein and Lao, under review

METHODS FOR INFERRING POPULATION SUBSTRUCTURE Wollstein and Lao, 2015 Investigative Genetics

METHODS FOR INFERRING POPULATION SUBSTRUCTURE Wollstein and Lao 2015

4) SOME EXAMPLES

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

EXAMPLE I:POPULATION SUBSTRUCTURE IN EUROPE: DATA MASSAGE “In particular, the Catalans have more genetic proximity with the French than with the Spanish; more with the Italians than with the Portuguese; and a little with the Swiss. While the Spanish have more proximity with the Portuguese than with the Catalans and very little with the French. Curious...”

EXAMPLE II:POPULATION SUBSTRUCTURE IN EUROPE: THE ROMANI Mendizabal and Lao et al, Current Biology 2012

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