Katie Peichel

Genetics of adaptation in sticklebacks – the roles of pleiotropy and linkage

How do organisms adapt to different environments?

: genetic variation (natural selection/evolutionary change) phenotypic variation

Sepecific questions –

:A few mutations of large effects or many of small effect?

:Genetic linkage/pleiotropy facilitate adaptation?

:What genes contribute to adaptation?

Threespine stickleback – small teleost fish; extensive phenotypes; replicate evolutionary events; divergent population can be crossed;

Ancestral marine populations; derived freshwater populations;

QTL mapping – crosses -> genetic map -> candidate genes -> molecular changes

Growth of genomic resources for threespine stickleback – Kingsley & Peichel 2007

What have we learned in the past 15 years?

: 28 QTL mapping studies to date (2001-2016)

:1034 QTL in 9 trait categories – morphology; reproduction; behavior

Many loci of smaller effect, relatively few of large effect, Peichel & Maques, 2017

QTL are clustered in the genome

Genetics of phenotypic evolution – Shapiro et al., 2004; Colosimo et al., Science 2005; Miller et al., 2007

What genes contribute to phenotypic evolution?

: coding mutations or regulatory mutations?

When the same phenotype evolve, are the same or different genes involved?

If the same genes are involved, is this due to new mutation or standing variation?

Are QTL clusters due to pleiotropy (a master mutation) or linkage (a mass of mutations)?

QTL clusters/genomic divergence on chromosome IV

16 kb haplotype contains 3 protein coding genes and 17 SNPs – Colosimo et al., Science, 2005; O’Brown 2015;

Eda gene affects on three phenotypes – Colosima, 2005; Mills et al., EvoDevo 2014; Greenwood et al., 2016

Pleiotropy or linkage? – schooling behavior?

: finer recomb. mapping, followed by functional experiments

Association mapping in Lake Washington – Kitano et al., 2008

：randomly sampling 1000 fish; genotyping; phenotyping for all traits known to map to QTL

Recomb. within the 16kb haplotypes – Sophie Archambeault

Total plate number is associated with SNP4 – S.A. & Luis Birtsch

Neuromast pattern is associated with SNP4 – S.A. & L.B.

Gill raker length is associated with SNP4 – S.A. & L.B.

Keel plate number is associated with LP2 – S.A. & L.B.

Pelvic spine

Some, but not all traits, map to the 16kb haplotype – S.A. & L.B.

Mostly pleiotropy and a little linkage?

What if we only look at low plated fish? – Colosimo et al., PLoS Biology 2004

Critical region is 600 bp.

Next steps: functional tests with CRISP/Cas9

Genetics of adaptation (pleiotropy or linkage/ selective forces?)

Ma Hansong

Supervision of mtDNA transmission

Another kind of genetics (non-Mendelian): relaxed replication; random segregation; biochemical threshold for disease phenotype

:Stochastic patterns encourage competition among genomes for transmission

Targeted restriction enzyme selection: - Xu et al., 2008

Basic rules – purifying selection (functional genomes); selfish selection;

Two selections can be balanced: stable heteroplasmy

A screen to identify nuclear loci modifying mt competition: deficiency kit (500 lines); heterozygous deletion

Two deletions increased Y genome: tam3/tam4

Matt Bawn

SalTy

Samonella – host specialization & genome degradation; evolution and acquisition of pathogenicity factor

Typhimurium Reference Strains

ARIBA: 110.1099/mgen.0.000131 – Hunt M. et al., Microbioal Genomes 2017

Recomb. Croucher et al., NAR 2014

UK Monophasic Epidemic

Salmonella Genomic Island - Petrovska, Lijana et al., 2016; 2018

South East Asia SalTy

South East Asia CHASRI

SGI4 recomb.

Gifsy

Frederik Hendrickx

Microgeographic adaptation – Richardson et al., 2014, TREE

Questions –

Resources of genetic variation: rate and direction of contemporary adaptation

Pogonus chalceus – carabid beetle – saltmarshes (SW/LW ecotypes)

Explore divergence at a genome-wide scale : RADseq of 4 population pairs + 1 SW and 1LW; de nov transcriptome sequencing;

General population structure – ecotype + geography

Differentiation across genome (SNP level) – BayeScan/BayEnv

Highly consistent genealogical pattern across (unlinked) outlier loci: SW associated alleles generally derived; diverged within a similar time frame ( 190 kya – late Pleistoc.)

Quantifying standing genetic variation

Jill Olofsson

Evolutionary history of adaptive traits

:Standing genetic variation and novel mutations

Alloteropsis semialata

Recurrent lateral gene transfer: Dunning et al. unpublished

Geographically restricted novel LGTs

Population genomics to trace the history of genomic novelties

RADSeq: structural population with limited gene flow – Olofsson et al., unpub.

Demographic history; Fst outliers in region of low recomb.

Novel LGTs often not in Fst outlier region

The LGT show polymorphic present/absent-pattern

Novel mutations are neutral in some populations:

Introgression of the mutation

Genomic fate of novel mutations: location (recomb. rate); demographic history/population processes (bottlenecks; drift; founder effect; gene flow); neutral and polymorphic in some populations but also be adaptative in different conditions

Elizabeth Duxbury

Selection by pathogens increases genetic variations

Abundant genetic variation in host disease susceptibility

Wider relevance of genetic variation in infection susceptibility

Natural selection -> genetic variation decrease; parasite selection -> genetic variation increase

Genetic variation maintained? Woolhouse et al., 2002

: new partial selective sweeps; host parasite co-evolution;

Genetic architecture of resistance: quantitative traits very polygenic

Study system – Drosophila (mel. Immi. Affinis; )

Sigma viruses (host specific; rhabdoviruses; negative sense, single-stranded RNA; cytoplasmic)

Compare natural vs non-natural infections

Experimal design

DSPR: Cogni et al. 2016

GWAS: Magwire et al., 2011

Ancestral state: always susceptible – continual evolution of new defences

Recent partial selective sweep – directional selection

Current – genetic architecture of resistance

Andrew Foote

Ancestral demography; killer whale; genomic diversity

Global distribution of local adaptive traits

Allelic surfing during range expansions: distance from orgin –

Evidence for and against low efficacy of selection to remove deleterious mutations

Killer whale densities

AquaMaps modelled suitable for killer whales

Global dataset of genomes

Drift and admixture

Admixture and secondary contact between North Pacific ecotypes

Whole genome estimates of theta

Runs of homozygosity

Allelic surfing during range expansions

Increase in the frequency of on-synonymous derived homozygous genotypes

Influence of demographic history on genome-wide differentiation – Foot et al., 2016

High latitude ecotypes show evidence for various things.

Hannes Svardal

Hybridization; adaptive divergence; cichlid radiation

Cichlids like to radiate - Brawand et al., 2014

Whole genome of 140 samples of 70 species

Prevalence and role of hybridization – hybrid swarm/within diverging lineages

Ancestral hybridization - Meier et al., 2017 – ABBA-BABA test

Ancestral hybridization helped species divergence – private/shared/hybridization derived

No excess divergence in neutral simulations

Molecular function of genes enriched for introgression

Hybridisation within the radiation

Triplets of Malawi species are inconsistent with tree-like relationships

Trees along the genome (TWISST): genome/introgression/control

Chrosome-scale differences in relatedness patterns

FISH supports inversions by fluorescent in-situ hybridization/cytogenetics@Sanger

Visual system and oxygen transport pathways enriched for non-synonymous diversity

Haplotype networks of these genes show allele sharing between two genetically distant deep adapted groups

Long introgression haplotypes consistent with adaptive introgression

David Marques

How repeatable + predictable is evolution?

: contingency; determinism

At genome level? Repeatability of adaptation

Admixture between divergent gene pools – threespine stickleback; haplochromine cichlid

Repeatability within catchment: parallel genomic divergence – islands; parallel genomic islands

Origin of Lake Constance stickleback? : mosaic hybrid zone – 12000 years ago

Admixture facilitated parallel adaptation; parallel genomic islands = admixture variation

Repeatability between radiations

Mark Ravinet

Human commensalism in House sparrows

Adaptation to human niche – anthrodependent taxa

:evolution via commensalism; dependent on human resources; bioproxies for himan migration and history

Jones 2013; Hume-Beaman 2016

Sparrows as a human commensal: strong association with human society

Model for adaptation to a human niche : orgin of human dependency; genomic signatures of adaptation to human niche; phenotypes

Population structure of Eurasian sparrows – whole-genme resequencing

Spanish/Italian/House – Bactrianus

Introgression in European house sparrows

How did commensalism arise? (following Neolithic revolution in Near East-10 Kyr BP)

Divergence with ongoing migration : site-frequency spectrum fastsimcoal2

Divergent selection between lineages - 1.03 millions SNPs

Signatures of sweeps in house only

COL11A1 – Marshall syndrome in humans

AMY2A – starch digestion in humans and dogs

Understanding commensalism – future work

Has commensalism arisen multiple times?

John Welch

Coadapted genomes and selection on hybrids

Hybrid genomes / heterozygosity / hybrid index – Christe et al., 2016

A fitness landscape: quantitative traits; optimizing selection; additive mutations; chains of substitutions connect P1 & P2; treated as constrained random walks; compare to unconstrained RW

Inbred lines – Wright 1922; 1977

Well adapted parents – Bieme et al., 2002

Heterogametic backcrosses – Noor et al., 2001

Inferring the fitness surface – Christe et al., 2016; White et al., 2011

Simple model predicts many broad-scale patterns; Interpolates between other approaches; Genome-wide predications: no need to identify anomalous regions

Sara Kurland

Genomic differentiation in sympatric brown trout populations

Brown trout (Salmo trutta)

Artificial sympatric populations

Natural sympatric populations

Gain genomic insights into natural populations : level of differentiation

Methods – WGS of 50 individuales; annotation; comparisons between populations

Higher divergence between artificial sympatric populations than natural ones;

Rus Hoelzel

Genomics of habitat choice and adaptative evolution in a deep-sea fish

Round-nosed Grenadier – White et al., 2010 – 180 -2200 m deep, high potential for larval drift

1000-2000 m is not an arbitrary boundary

WGS (PRJNA417902)

WGS of different species at different depth – Gaither et al., 2018

32 significant outlier SNPs

Comparing assessment of LD against physical lineage along contigs (1000m only) suggested concerted evolution

Juveniles found in relatively shallow water only

RADseq/SNPs, PCA no support for assortative mating

ROCK1, functions associated with energy consumption

Clarissa Ferreira de Carvalho

Population epigenetics in Timema cristinae stick-insects

DNA methylation in Eukaryotes

In plants : interactions with environment & local adaptation (Dubin et al., 2015) ; role suppressing TEs (Zhang et al., 2006)

In animals: plasticity (Abramon et al., 2017); insects (Bewick et al., 2016)

Natural methylation variation

Nosil et al., 2012

Methylation profile in the insect, how it varies in space and mechanism

Methods: sampling design and sequencing – geographical distances; host plants, clilmate variables, altitude; 2 adults female from each population; WGS+RADseq; bisulfite sequencing

Results: degree of methylation

Bisulfite conversion – 99.5% efficiency

Spatial patterns (height); no clear cluster for host plants; heritability is low;

MACAU, bionomial mixed model - Lea et al., 2015

: differences between ecotypes; relatedness matrix: RAD-Seq

Samuel Lewis

Somatic piRNA

Small RNA mechanism

piRNA pathway is germline-specific

Morazzani et al., PLoS Pathogens; Mondal et al., 2018 PLoS Genetics

Aims: How common in soma; ancestral or derived? Functions in different lineages?

Tissue-specific small RNA sequencing across 20 arthropods

Somatic/germline tissues dissected from females; same tissues dissected from males of 10 species; total RNA and small RNA content of each tissue sequenced

: Germline piRNAs are conserved across arthropods

: piRNAs have been lost in male bumble germline – ovary/testis

: somatic piRNAs are common across arthropods

Arthropod piRNAs were ancestrally somatic

: lost at least 4 times independently

Small RNA-Seq, Genome >> TE+ mRNA

Somatic piRNAs target TEs, mRNAs and virues

Lara Urban

Regulatory mutational processes in 1,188 human tumors

Cancer as an evolutionary disease, starts with one cell mutates

Evolution of cancer: time-bottleneck-genetic heterogeneity

Inter- and intra tumour heterogeneity

PCAWG – Pan-cancer analysis of whole genomes – 10 data centres, 800 scientists, 2800 patients, WGS

27 cancer types

Regulatory impact of genetic variants: mutational signatures; NMF; final signatures – Alexandrov et al., 2013

Links between gene expression and mutational signatures: 40 signatures – 18k genes; 28 signatures – 1176 genes; gene enrichment (Premi et al., 2015)

Gene-level analysis: (cancer) genes, e.g. Signature 4 – CYP26A1

Integrated analysis

Aida Andres

Human populations - Low genetic diversity/population differentiation

Ambient temperature

Transcient receptor potential (TRP) ion channels

Activated by menthol; high cold tolerance in two families of hibernating mammals – Matos-Cruz et al., 2017

TRPM8: 1000 genomes data; allele frequencies correlation with temperature

Phylogenetic generalized least squares (PGLS); Generalised Linear Mixed Model (GLMM) – Key et al., bioRxiv 2017; PLoS Genetics in press

Signatures of local adaptation

No clear LD signatures of a hard sweep

TRPM8 models of positive selection – ABC method – Peter et al., PLoS Genetics 2012; ABC results

TRPM8 signatures of positive selection – Time = 26000 years (21000-49000)

Phenotypic associations/consequences

Migraine

Anders Eriksson

Reconstructing the history of human inflammation regulation

Interleukin (IL) receptor gene family – Fumagalli et al., 2009

IL-36 family of cytokines – Walsh & Fallon 2016

IL-36 RN – receptor antagonist -> severe postular psoriasis

What is the history of this locus?

Four major haplotype groups – deep history

Do haplogroups have different gene expression patterns? – from 400 donors, multiple tissues

HG2 is down-regulated relative to HG4

Ancient DNA, 1170 samples, 36000 BCE to -60 AD

The history of gene expression of IL36RN in West Eurasia (spread of farming/last glacial maximum)

Link to pathogen exposure during last glaciation and spread of farming?