Population and evolutionary genetics

Genes and language, Part VII: Population and evolutionary genetics DGFS Summer School 2013 Berlin 26th 30th of August, 2013 Language and Genetics Max Planck Institute for Psycholinguistics Nijmegen The Netherlands 1

Overview Part VII Population genetics Evolutionary genetics New developments Innateness Overview 12

Nuclear and mitochondrial DNA mitochondrial DNA (mtdna) nuclear membrane Genome nuclear DNA cell membrane mitochondria nucleus mitochondrial membrane Nuclear and mitochondrial DNA 13

Nuclear and mitochondrial DNA Nuclear and mitochondrial DNA Some genes (energy production) Own genetic code D-loop hypervariable regions (HVR-I & HVR-II) Maternal inheritance 14

Nuclear and mitochondrial DNA Chromosomes: single linear molecules of DNA Karyotype = all chromosomes in the nucleus Humans: 23 pairs of chromosomes (diploid) 22 pairs autosomes 1 pair sex chromosomes XX= XY= Inheritance: X & autosomes: both parents Y: paternal inheritance Nuclear and mitochondrial DNA 15

Nuclear and mitochondrial DNA the inheritance of the nuclear genome recombination, independent assortment autosome pair XY sex chromosomes parents offspring XX mtdna XY Nuclear and mitochondrial DNA XY XX 16

Population, locus, allele & gene pool Bi-allelic autosomal locus A & a Aa Individuals Population AA aa Aa AA Aa Homozygous Aa aa Aa Heterozygous Population, locus, allele & gene pool 17

Population, locus, allele & gene pool Bi-allelic autosomal locus A & a Allele frequencies pa & pa Genotype frequencies paa, paa & paa Aa AA aa Aa Aa AA Aa Aa Aa AA aa aa Aa aa Aa t pa, pa; paa, paa & paa conditions & factors Aa Aa aa AA Aa aa aa Aa... AA t+1 p'a, p'a; p'aa, p'aa & p'aa t+n Time Population, locus, allele & gene pool 18

The Hardy-Weinberg Equilibrium Hardy-Weinberg Equilibrium (HWE): if nothing interesting happens no change simple null hypothesis Aa AA aa Aa Aa AA Aa Aa aa AA aa Aa Aa t pa, pa; paa, paa & paa infinite population no mutation no natural selection random mating no migration Aa AA Aa aa Aa t+1 pa, pa; paa, paa & paa Time The Hardy-Weinberg Equilibrium Dan Dediu 19

Genetic drift, bottlenecks & founder effects Finite populations reproduction = random sampling Genetic drift 1

Genetic drift, bottlenecks & founder effects Finite populations reproduction = random sampling Bottlenecks founder effect (e.g., SLI on Robinson Crusoe Island) Bottlenecks 1

Genetic drift, bottlenecks & founder effects Finite populations reproduction = random sampling Bottlenecks founder effect (Effective) population size, Ne Effect Danpopulation Dediu size (Ne) 1

Genetic drift, bottlenecks & founder effects Finite populations reproduction = random sampling Bottlenecks founder effect (Effective) population size, Ne reduces genetic diversity Genetic drift 1

Mutation Mutation changes the genetic information (e.g., A a) Many types: point mutation, chromosomal rearrangements, gene duplications, CNVs... increases genetic diversity Mutation 1

Selection Selection differential survival and reproduction Selection 1

Selection Selection differential survival and reproduction Types: natural Types selection DanofDediu vs sexual vs artificial 1

Selection Selection differential survival and reproduction Types: Heterozygote advantage Stabilizing/Purifying/ Negative vs Types selection DanofDediu vs Directional/Positive Disruptive/Balancing Fitness Frequencydependent ne ga ti ve sit po ive Phenotype frequency 1

Selection Selection differential survival and reproduction Walking the fitness landscape Fitness Dan landscape Dediu 1

Selection Selection differential survival and reproduction Walking the fitness landscape Dynamic fitness landscape Co-evolution & arms races Niche construction Fitness Dan landscape Dediu 1

Detecting selection Detecting selection: Between species data Within species data Detecting selection 12

Detecting selection Between species data synonymous vs non-synonymous substitutions Detecting selection 12

Detecting selection Between species data synonymous vs non-synonymous substitutions ~ same probability if they are neutral < 1 purifying selection dn/ds (or Ka/Ks) ratio 1 neutrality > 1 positive selection homologous genes between species (human chimp) multiple selective changes ongoing/recurrent selection Detecting selection 12

Detecting selection Within species data differences between populations (FST): positive selection in one population (partial) reproductive isolation Frequency of sickle-cell allele (HbS) Detecting selection 12

Detecting selection Within species data differences between populations (FST): positive selection in one population (partial) reproductive isolation same patterns: demographic history (bottlenecks) Population 2 Population 1 strong positive selection for A1 drift strong founder effect/bottleneck Source population Detecting selection 12

Detecting selection Within species data differences between populations selective sweep Chromosomes (within individuals) Neutral alleles Mutation/introgression 1 Detecting selection Time 12

Detecting selection Within species data differences between populations selective sweep Chromosomes (within individuals) Neutral alleles Adaptive (selected) allele 1 Detecting selection Time 12

Detecting selection Within species data differences between populations selective sweep Adaptive allele spreads 1 Detecting selection 2 Time 12

Detecting selection Within species data differences between populations selective sweep Linked loci (incl. neutral alleles) hitchhike Haplotype Adaptive allele spreads 1 Detecting selection Recombination 2 Time 12

Detecting selection Within species data differences between populations selective sweep Incomplete/partial sweep 1 Detecting selection 2 Time 13

Detecting selection Within species data differences between populations selective sweep Incomplete/partial sweep 1 Detecting selection 2 Complete sweep Time 13

Detecting selection Within species data differences between populations selective sweep Incomplete/partial sweep Complete sweep Low diversity + excess of rare alleles High frequency of derived alleles Long haplotypes Detecting selection 13

Detecting selection is hard: the FOXP2 case Enard et al. (2002): top 5% most conserved proteins 2 AA substitutions on the human lineage in exon 7 Human specific AA substitutions in exon 7 Selection on FOXP2 13

Detecting selection is hard: the FOXP2 case Enard et al. (2002): top 5% most conserved proteins 2 AA substitutions on the human lineage in exon 7 tests of selection: more low-frequency alleles (Tajima's D) & more derived alleles at high frequency (H) both highly significant strong selective sweep Selection on FOXP2 13

Detecting selection is hard: the FOXP2 case Enard et al. (2002) 200kya, modern humans Krause et al. (2007): Neandertal adna same 2AA in FOXP2 as us on same haplotype human specific FOXP2 was shared with the Neandertals and much older (400-800kya) Selection on FOXP2 13

Detecting selection is hard: the FOXP2 case Enard et al. (2002) 200kya, modern humans Krause et al. (2007) shared with N, 400-800kya? Ptak et al. (2009): human specific 2AA are not the target of the selective sweep! 2nd selective sweep in moderns after split from Neanderthals Selection on FOXP2 13

Detecting selection is hard: the FOXP2 case Enard et al. (2002) 200kya, modern humans Krause et al. (2007) shared with N, 400-800kya? Ptak et al. (2009) 2nd sweep not affecting the 2AA Maricic et al. (2012): intron 8 (POU3F2 binding site) derived allele in moderns but not in Neandertals and Denisovans FOXP2 regulation? human specific change, the 2nd sweep! but: old allele (N & D) ~10% in African populations... Selection on FOXP2 13

Detecting selection is hard: the FOXP2 case Enard et al. (2002) 200kya, modern humans Krause et al. (2007) shared with N, 400-800kya? Ptak et al. (2009) 2nd sweep not affecting the 2AA Maricic et al. (2012): intron 8 (POU3F2 binding site)? Hard to: - detect selection, - date it, - localize it and - interpret it! Selection on FOXP2 13

Databases Data sources:... Databases 14

Population structure Non-random mating inbreeding assortative mating population subdivision Population structure 14

Population structure Non-random mating inbreeding assortative mating population subdivision gene flow/admixture Population structure 14

Extending the phenotype Classical phenotypes: morphology, physiology, behaviour Extended phenotypes: beyond the individual Dawkins, R. (1982). The Extended Phenotype. Oxford University Press: Oxford, UK. The extended Dan Dediuphenotype 4

Extending the phenotype Odling-Smee,, John F.; Laland, Kevin N.; Feldman, Marcus W. (2003). Niche Construction The Neglected Process in Evolution. Princeton University Press. - standard view: niches are fixed and organisms adapt to them - walking on a fixed fitness landscape - organisms do change their niche they construct one feedback on organisms - the constructed niche could be transgenerational (inherited across generations) Selective pressures Niche construction Niche Danconstruction Dediu 4

Extending the phenotype Laland, K. N., Odling-Smee, J., & Myles, S. (2010). How culture shaped the human genome: bringing genetics and the human sciences together. Nature Reviews Genetics 11:137148. - farming in general amylase gene immune system lactose tolerance - tool use hand Cultural niche construction & gene-culture co-evolution 4

Extending the phenotype Laland, K. N., Odling-Smee, J., & Myles, S. (2010). How culture shaped the human genome: bringing genetics and the human sciences together. Nature Reviews Genetics 11:137148. - culture co-evolutionary cycle Cultural niche construction & gene-culture co-evolution 4

New developments in evolutionary theory classic evolutionary theory: Modern Synthesis/Neo-Darwinism ~ 1930 1950: population genetics + Mendelian genetics + (gradual) natural selection R.A. Fisher, T. Dobzhansky, S. Wright, J.B.S. Haldane, E. Mayr... M. Kimura ('68), King & Jukes ('69): the Neutral Theory most molecular changes are neutral due to mutation & drift - null model - the molecular clock : neutral mutations accumulate at constant rate = mutation rate (μ) The Modern Synthesis (Neo-Darwinism) Dan Dediu 15

New developments in evolutionary theory classic evolutionary theory: Modern Synthesis/Neo-Darwinism ~ 1930 1950: population genetics + Mendelian genetics + (gradual) natural selection R.A. Fisher, T. Dobzhansky, S. Wright, J.B.S. Haldane, E. Mayr... M. Kimura ('68), King & Jukes ('69): the Neutral Theory T. Ohta ('73): the Nearly Neutral Theory - slightly (dis)advantageous mutations: selection coefficient (s) - population (effective) size (Ne) Ne s << 1 genetic drift; otherwise selection effectively neutral in small populations same mutation under natural selection in large populations The Modern Synthesis (Neo-Darwinism) Dan Dediu 15

New developments in evolutionary theory classic evolutionary theory: Modern Synthesis/Neo-Darwinism ~ 1930 1950: population genetics + Mendelian genetics + (gradual) natural selection R.A. Fisher, T. Dobzhansky, S. Wright, J.B.S. Haldane, E. Mayr... M. Kimura ('68), King & Jukes ('69): the Neutral Theory T. Ohta ('73): the Nearly Neutral Theory 1960s: Hamilton, Williams, Maynard Smith gene-centered The Modern Synthesis (Neo-Darwinism) Dan Dediu 15

Evolutionary developmental biology Developmental biology mostly left out of Neo-Darwinism Development was seen as a black box ; simple one gene one trait Evo-Devo Gene1 Trait1 Gene2 Trait2...... GeneN TraitN 15

Evolutionary developmental biology Developmental biology mostly left out of Neo-Darwinism Development was seen as a black box ; simple one gene one trait; but: complex, coordinated & constrained process modularity genetic cascades gene regulation, master genes (e.g Hox) Evo-Devo 16

Evolutionary developmental biology Developmental biology mostly left out of Neo-Darwinism Development was seen as a black box ; simple one gene one trait; but: complex, coordinated & constrained process modularity Butterfly wing mutants Hindwing evolution genetic cascades gene regulation, master genes (e.g Hox) homology (retention), reuse & innovation Evo-Devo 16

Evolutionary developmental biology gluteus Developmental biology mostly left out of Neo-Darwinism Development was seen as a black box ; simple one gene one trait; but: new tendons complex, coordinated & constrained process modularity genetic cascades gene regulation, master genes (e.g Hox) homology (retention), reuse & innovation developmental plasticity - new phenotypes reorganization of old phenotypes Evo-Devo 16

Epigenetics Relatively old idea Waddington (1942): epigenetic landscape (cell fate in development) gene regulation in development heritable information not involving the DNA sequence - self-sustaining metabolic loops: - with or without gene regulation - structural inheritance (spatial templating): - prions, patterns of cilia (Paramecium) - RNA-mediated: - RNA interference (gene silencing) - chromatin-mediated Epigenetics 16

Epigenetics Widespread Involved in developmenet, normal functioning & disease Epigenetics 17

Epigenetics Widespread Involved in developmenet, normal functioning & disease Some cases of trans-generational transmission Epigenetics 17

Horizontal genetic transfer Microorganisms got left out as well Neo-Darwinism focused on higher animals and plants mostly vertical transmission largely sexual reproduction relatively well-defined species HGT 17

Horizontal genetic transfer Microorganisms got left out as well Neo-Darwinism focused on higher animals and plants mostly vertical transmission massive & widespread HGT largely sexual reproduction asexual & sexual relatively well-defined species more fluid HGT 17

Horizontal genetic transfer Microorganisms got left out as well Neo-Darwinism focused on higher animals and plants Tree of Life (TOL) HGT 17

Horizontal genetic transfer Microorganisms got left out as well Neo-Darwinism focused on higher animals and plants Tree of Life (TOL) Symbiosis HGT 17

What does innate actually mean? Number of arms? Muscular mass? A person's sex? A person's gender? A crocodile's sex? Innateness 7

What does innate actually mean? Speaking Dutch? Speaking any language? Beaver's tree cutting? A beravers' dam? New York? Innateness 7

Several tentative definitions Mameli, M., & Bateson, P. (2006). Innateness and the Sciences. Biology and Philosophy, 21:155188. Mameli, M., & Bateson, P. (2011). An evaluation of the concept of innateness. Philosoph. Trans. Royal Soc. B, 366:436443. 1. Innate = not acquired the trait is not there to start with but is acquired later all traits are acquired! Innateness 7

Several tentative definitions Mameli, M., & Bateson, P. (2006). Innateness and the Sciences. Biology and Philosophy, 21:155188. Mameli, M., & Bateson, P. (2011). An evaluation of the concept of innateness. Philosoph. Trans. Royal Soc. B, 366:436443. 1. Innate = not acquired 2. Innate = present at birth - secondary sexual characters - parenting behaviors - prenatal learning (intonation) Innateness 7

Several tentative definitions Mameli, M., & Bateson, P. (2006). Innateness and the Sciences. Biology and Philosophy, 21:155188. Mameli, M., & Bateson, P. (2011). An evaluation of the concept of innateness. Philosoph. Trans. Royal Soc. B, 366:436443. 1. Innate = not acquired 2. Innate = present at birth 3. Innate = reliably appears at a particular stage - learning does that as well (writing) Innateness 8

Several tentative definitions Mameli, M., & Bateson, P. (2006). Innateness and the Sciences. Biology and Philosophy, 21:155188. Mameli, M., & Bateson, P. (2011). An evaluation of the concept of innateness. Philosoph. Trans. Royal Soc. B, 366:436443. 1. Innate = not acquired 2. Innate = present at birth 3. Innate = reliably appears at a particular stage 4. Innate = genetically determined - more than genes are required for development Innateness 8

Several tentative definitions Mameli, M., & Bateson, P. (2006). Innateness and the Sciences. Biology and Philosophy, 21:155188. Mameli, M., & Bateson, P. (2011). An evaluation of the concept of innateness. Philosoph. Trans. Royal Soc. B, 366:436443. 1. Innate = not acquired 2. Innate = present at birth 3. Innate = reliably appears at a particular stage 4. Innate = genetically determined Innateness 8

Several tentative definitions 6. Innate = genetically encoded - unclear what genetic information is: a) causal link gene phenotype b) selection links genes phenotype Innateness 8

Several tentative definitions 6. Innate = genetically encoded 7. Innate = no extraction of information from the environment - Chomsky's poverty of the stimulus scars, calluses environment-as-support environment-as-information Innateness 8

Several tentative definitions 6. Innate = genetically encoded 7. Innate = no extraction of information from the environment 9. Innate = can't produce variant forms by environmental manipulation thalidomide on number of hands microgravity Innateness 8

Several tentative definitions 6. Innate = genetically encoded 7. Innate = no extraction of information from the environment 11.Innate = can't produce variant forms by statistically normal environmental manipulation queens in eusocial insects < 10% changes in environment Innateness 8

Several tentative definitions 6. Innate = genetically encoded 7. Innate = no extraction of information from the environment 12.Innate = can't produce variant forms by evolutionarily normal environmental manipulation 13.Innate = highly heritable 14.Innate = not learned Innateness 8

Several tentative definitions 18.Innate = (i) it is not produced by a mechanism adapted to map diﬀerent environmental conditions onto diﬀerent phenotypes, and (ii) it doesn t result from the impact on development of evolutionarily abnormal environmental factors - generalization of learning adaptive plasticity adapted mechanism Innateness 8

Several tentative definitions 18.Innate = (i) it is not produced by a mechanism adapted to map diﬀerent environmental conditions onto diﬀerent phenotypes, and (ii) it doesn t result from the impact on development of evolutionarily abnormal environmental factors - changes in environment changes in innateness status - crocodile sex determinism vs crocodile sex-specific behaviors environmental triggers switch on developmental programs Innateness 9

Several tentative definitions 18.Innate = (i) it is not produced by a mechanism adapted to map diﬀerent environmental conditions onto diﬀerent phenotypes, and (ii) it doesn t result from the impact on development of evolutionarily abnormal environmental factors 19.Innate = generatively entrenched in the design of an adaptive feature - basic intuition: innate traits are non-malleable (robust) developmentally and/or post-developmentally Innateness 9

Several tentative definitions 18.Innate = (i) it is not produced by a mechanism adapted to map diﬀerent environmental conditions onto diﬀerent phenotypes, and (ii) it doesn t result from the impact on development of evolutionarily abnormal environmental factors 19.Innate = generatively entrenched in the design of an adaptive feature - other features depend causally on this hubs in feature networks Innateness 9

Several tentative definitions 21(22).Innate = (post-)developmentally canalized - norm of reaction = phenotypes of a single genotype when environment varies Innateness 9

Several tentative definitions 21(22).Innate = (post-)developmentally canalized - norm of reaction = phenotypes of a single genotype when environment varies - phenocopy = environmentally-induced phenotype identical to one produced by a different genotype straw mutation silver nitrate Innateness 9

Several tentative definitions 21(22).Innate = (post-)developmentally canalized - learning can be canalized (e.g., imprinting in birds) - genetic disorders are not canalized Innateness 9

Several tentative definitions 21(22).Innate = (post-)developmentally canalized 23.Innate = species-typical - what is typical/normal? - learned stuff can be typical - genetic diseases are not species-typical Innateness 9

Several tentative definitions 21(22).Innate = (post-)developmentally canalized 23.Innate = species-typical 25.Innate = standard Darwinian adaptation - genetic disorder & new mutations are not innate - learned traits are results of standard Darwinian adaptations (birdsong) - spandrels/exaptations/pre-adaptations are not innate Innateness 9

Several tentative definitions 21(22).Innate = (post-)developmentally canalized 23.Innate = species-typical 25.Innate = standard Darwinian adaptation Innateness 9

Several tentative definitions Each captures an aspect of innateness innateness score A priori non-equivalent: Innateness 1

Several tentative definitions Each captures an aspect of innateness innateness score A priori non-equivalent: 27.Innate = high innateness score Innateness 1

So, is Innateness innate? 1

Conclusions Evolutionary theory complex and rapidly evolving Genetics/genomics extremely important contributions Constrains language evolution theorizing Thanks to: Alejandrina Cristia, Sarah Graham, Steve Levinson Funding: Netherlands Organisation for Scientific Research ( Conclusions ) Vidi grant 276-70-022 1

Suggested reading Books: Jobling, M. A., Hurles, M., & Tyler-Smith, C. (2004). Human Evolutionary Genetics: Origins, Peoples and Disease. Garland Science: NY. Halliburton, R. (2004). Introduction to population genetics. Pearson Eduction Inc.: Upper Saddle River. Carroll, S. B. (2011). Endless Forms Most Beautiful: The New Science of Evo Devo. Quercus Publishing. Koonin, E. V. (2012). The Logic of Chance: The Nature and Origin of Biological Evolution. Pearson Education, Inc.: NJ, USA. Suggested readings 1

Suggested reading Population and evolutionary genetics: Hurst, L. D. (2009). Fundamental concepts in genetics: genetics and the understanding of selection. Nat Rev Genet 10:8393. doi:10.1038/nrg2506 Charlesworth, B. (2009). Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation. Nat Rev Genet 10:195205. doi:10.1038/nrg2526 Jablonka, E., & Raz, G. (2009). Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. The Quarterly Review of Biology 84:131176. Koonin, E. V. (2009). Darwinian evolution in the light of genomics. Nucleic Acids Res 37:10111034. doi:10.1093/nar/gkp089 Innateness: Mameli, M., & Bateson, P. (2006). Innateness and the Sciences. Biology and Philosophy 21:155188. Mameli, M., & Bateson, P. (2011). An evaluation of the concept of innateness. Philosophical Transactions of the Royal Society B: Biological Sciences 366:436443. doi:10.1098/rstb.2010.0174 Suggested readings 1

Suggested reading Gene-culture co-evolution/niche construction: Laland, K. N., Odling-Smee, J., & Myles, S. (2010). How culture shaped the human genome: bringing genetics and the human sciences together. Nat Rev Genet 11:137148. doi:10.1038/nrg2734 Fisher, S. E., & Ridley, M. (2013). Culture, Genes, and the Human Revolution. Science 340:929930. doi:10.1126/science.1236171 Suggested readings 1