Bayesian Inference over Recombinant DNA Sequences Apresentação efectuada no âmbito do Estágio da Licenciatura em Biologia – Ramo Científico-tecnológico

Bayesian Inference over Bayesian Inference over Recombinant DNA Recombinant DNA

SequencesSequencesApresentação efectuada no âmbito do Estágio da Licenciatura em Apresentação efectuada no âmbito do Estágio da Licenciatura em

Biologia – Ramo Científico-tecnológico Biologia – Ramo Científico-tecnológico

João Miguel dos Santos LourençoJoão Miguel dos Santos LourençoOrientador Interno: Prof. Doutor Nuno Ferrand de Almeida (FCUP)Orientador Interno: Prof. Doutor Nuno Ferrand de Almeida (FCUP)

Orientador Externo: Stuart Baird (CBGP, Montpellier)Orientador Externo: Stuart Baird (CBGP, Montpellier)

Porto, 25 de Outubro de 2007Porto, 25 de Outubro de 2007

Departamento de Zoologia Departamento de Zoologia e Antropologiae Antropologia

IntroductionIntroduction

Admixture EventsAdmixture Events

Figura 3. Prováveis zonas de refúgio do coelho europeu na Península Ibérica durante as glaciações do Pleistocénico (Branco et al., 2002).

Figura 2. Variação da temperatura e do volume de gelo, durante os últimos ciclos de glaciação do Pleistocénico (“Ice Age," Wikipedia: The Free Encyclopedia).

Figura 1. Coelho europeu (Oryctolagus

cuniculus).

Admixture EventsAdmixture Events

Lepus granatensisLepus granatensis

Figura 5. Rede Median-Joining dos haplótipos do locus Hprt1 do cromosoma X do coelho europeu (Geraldes et al., 2006).

Figura 4. Página inicial do artigo de Geraldes et al. (2006).

Fisher’s JunctionsFisher’s Junctions

Junção

Crossoverdurante a meiose

Origem 1 Origem 2

Geração F1

Figura 6. Esquema que ilustra a formação de Junções de Fisher (adaptado de Baird, 2006)

► Recombination instead of mutation

► Labels that identify the sources of abutting DNA

► Inference about chronology and geography of contact

ObjectiveObjective►To test, in a Bayesian framework, the To test, in a Bayesian framework, the

occurrence of Fisher’s junctions in occurrence of Fisher’s junctions in locuslocus Hprt1 of the X chromosome of Hprt1 of the X chromosome of the European Rabit (the European Rabit (Orictolagus Orictolagus cuniculuscuniculus))

► Infer about the chronology of contact Infer about the chronology of contact events between the two sub-species of events between the two sub-species of the European Rabittthe European Rabitt

Materials and Materials and MethodsMethods

DNA SequencesDNA Sequences►43 sequences of male rabbits►Source:

Geraldes et al. (2006) GeneBank Data Libraries (accession nos. DQ306448-DQ306490 )

►Outgroup: Hare (Lepus granatensis)►Alignment: BioEdit (Hall, 1999) ►1552 bp

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L. granatensis G T A A C T C G G T T A G C C T ~ T C A T ~ ~ ~ C C ~ T T C ~ ~ ~ ~ ~ C C A G A ~G C T T G T C C G A A C C G A G C C ~ C T G A C G G ~ A T C A A A C A A A G G A A A T T T A A G G G

Ver1827 (H1) . . . . . . . A . A . . . . . . . . T . G . . . . . C . . G C G . . . A A . . G C . . C C A . . . T . . A . A . . T A G . . . . T . . T T . . G G . . . . . A . ~ . . . . . . G . . .Vau1 (H1) . . . . . . . A . A . . . . . . . . T . G . . . . . C . . G C G . . . A A . . G C . . C C A . . . T . . A . A . . T A G . . . . T . . T T . . G G . . . . . A . ~ . . . . . . G . . .Alt120 (H1) . . . . . . . A . A . . . . . . . . T . G . . . . . C . . G C G . . . A A . . G C . . C C A . . . T . . A . A . . T A G . . . . T . . T T . . G G . . . . . A . ~ . . . . . . G . . .Alic1 (H11) . . . . . . . . A A C . . A . . A G T . . . T G . . C . . G C G . . . A A . . G C A . C C A . . . T . . A . A . . T A G . . . G T . . T T . . G . . . . . . A . ~ . . . . . . G . . .

Alt107 (H12) . . . . . . . . A A C . . . . . A . . . . . T G . . C . . G C G . . . A A . . G C A . C C A . . . T . . A . A . . T A G . . . G T . . T T . . G . . T . . . A . ~ . . . . . . G . . .Cau19 (H2) . . . . . . . A . A . . . . . . . . T . . . . . . . C . . G C G . . . A A . . G C . . C C A . . . T . . A . A . . T A G . . . . T . . T T . . G G . . . . . A . ~ . . . . . . G . . .Don6 (H25) . . . . . . T . A A C . A . . . A . . . . . T G . . C . . G C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . . G G G . . . . A . ~ . . . . . . G . . .Lrj3 (H9) . . . . . . . . A A C . A . . . A . . . . . T G . . C . . G C G . . . A A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . T G G . . . . . A . ~ . . . . . . G . . .

Cue3 (H9) . . . . . . . . A A C . A . . . A . . . . . T G . . C . . G C G . . . A A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . T G G . . . . . A . ~ . . . . . . G . . .Luc9 (H22) . . . . . . . . . G . . . . . . . . . . . . T G . . C ~ ~ G C G . . . A A . . G C A . C C A . . . T . . A . A . . T A G . . . G T . . T T . . G . . . . . . A . ~ . . . . . . G . . .

Gal25c3 (H14) . . . . . . . . A A C . . . . . A . . . . . T G . . C . . G C G . . . A A . . G C C . C C A . . . T . . A . A . . T A G . . . G T A . T T . . G . . . . . . A . ~ . . . . . . G . . .Vrl1 (H14) . . . . . . . . A A C . . . . . A . . . . . T G . . C . . G C G . . . A A . . G C C . C C A . . . T . . A . A . . T A G . . . G T A . T T . . G . . . . . . A . ~ . . . . . . G . . .Vrl7 (H14) . . . . . . . . A A C . . . . . A . . . . . T G . . C . . G C G . . . A A . . G C C . C C A . . . T . . A . A . . T A G . . . G T A . T T . . G . . . . . . A . ~ . . . . . . G . . .

Zam1 (H8) . . . . . . . A . A . G . . . . . . T . . . . . T . C . . G G C G A . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A ALuc4 (H21) A . . C . . . . . A . . . . . . . . T . G . . . . . C . . G C G . . . . A . A G T . . C G . . . . T . . . . T . A . . . T C . G . . . G G . . G G . . G ~ T . . ~ . . . . . . . A . .Zrg16 (H4) . . . . . . . A . A . G . . . . . . T . G . . . T . C . . G C G . . . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A AZam20 (H4) . . . . . . . A . A . G . . . . . . T . G . . . T . C . . G G C G A . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A A

Lrj6 (H4) . . . . . . . A . A . G . . . . . . T . G . . . T . C . . G G C G A . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A ACue1 (H4) . . . . . . . A . A . G . . . . . . T . G . . . T . C . . G G C G A . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A ABra1 (H4) . . . . . . . A . A . G . . . . . . T . G . . . T . C . . G G C G A . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A ALuc17 (H4) . . . . . . . A . A . G . . . . . . T . G . . . T . C . . G G C G A . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A A

VV1 1/94 (H4) . . . . . . . A . A . G . . . . . . T . G . . . T . C . . G G C G A . . . . A G T . . C G . ~ ~ ~ . C . . . . . . . . . T C . G . . T G G . . G G . . G . T . . . . . . . . . . A A AId85 (H26) . . . . . . . . . A . . . . T . . . T T G . . . . . C . . G G C G A . . . . A G T . . C G . . . . T . . . . T . . . . . T C . G . . . G G . . G G . . G ~ T . . ~ . . . . . . . A . .Tol25 (H16) . . . . . . . A . A . . . . . . . . T . G . . . . . T . . G G C G A . . . G A G T . . . G . . . . T . . . T . . . . . . T C A G . . . G G . . G G . . G . T . . ~ . . . . . . . A . .Cre1 (H19) . . . . . . . A . A . . . . . . . . T . G T T G . T C . . G G C G A . . . G A G T . . . G . . . . T . . . . . . . . . . T C . G . . . G G . . G G . . G . T . . ~ . . . . . . . A . .

Vdm12 (H19) . . . . . . . A . A . . . . . . . . T . G . . . . T C . . G G C G A . . . G A G T . . . G . . . . T . . . . . . . . . . T C . G . . . G G . . G G . . G . T . . ~ . . . . . . . A . .Amo2 (H20) . . . . . C . . . A . G . . . . . . T . G . . . . . C . . G G C G A . . . . A G T . . . G . . . . T C . . . . . . . . . T C . G . . . G G . . G G . . G . T . . . . . . . . . . A . A

Pep18 (H3) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . . . A . .Zrg20 (H5) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T A . T T . . . G . . G . T . . ~ . . . . . . . A . .Pfr5 (H5) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T A . T T . . . G . . G . T . . ~ . . . . . . . A . .Rsl4 (H6) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . . C . T C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . . . A . .Rsl10 (H6) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . . C . T C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . . . A . .Bnv3 (H7) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . G . A . .Mdr7 (H10) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . . . A . .Cat12 (H13) . ~ . . . . . . A A C . . . . . . . . . . . T G . . C . . G C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . . . A . .Pfr1 (H23) . . G . . . . . . G . . . . . . . . . . . . T G . . C . . G C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ ~ ~ ~ ~ ~ . . A . .Elv3 (H27) . . . . . . . . . G . . . . . A . . . . . . T G . . C . . . C G . . . . A . . G C . . C C A . . . T . . A . A . . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . . . A . .Tl50 (H17) . . . . . . . . . G . . . . . . . . . . . . T G . . C . . . C G . . . . A . . G C . . C C A . . . T . . A . A . . . A G . . . G T . . T T . . . G . . G . T . A ~ . . . . . . . A . .Tol64 (H18) . . . . . . . . . G C . . . . . . . T . G . . . . . C . . G C G . . T . A . . G C . . C C A . . . T . . A . A G . T A G . . . G T . . T T . . . G . . G . T . . ~ . . . . . . . A . .

Pfr7 (H24) . . . . T . . A . A . . . . T . . . T T G . . . . . C . . G G C G A . . . . A G T . . C G . . . . T . T . . T . . . . . T C . G . . . G G . . G G . . . . . A . ~ . . . . . . G . . .Bra13 (H15) . . . . T . . A . A . . . . T . . . T T G . . . . . C . . G G C G A . . . . A G T . . C G . . . . T . . . . T . . . . . T C . G . . . G G ~ . G G . . . . . A . ~ . . . . . . G . . .Vrl4 (H15) . . . . T . . A . A . . . . T . . . T T G . . . . . C . . G G C G A . . . . A G T . . C G . . . . T . . . . T . . . . . T C . G . . . G G ~ . G G . . . . . A . ~ . . . . . . G . . .Elv6 (H28) . . . . T . . . . A . . . . T . . . T T G . . . . . C . . G G C G A . . . . A G T . . C G . . . . T . T . . T . . . . . A C . G . . . G G . . G G . . . . . A . ~ . . . . . . G . . .

Diagnostic mutationsDiagnostic mutations

Figura 7. Mapa de polimorfismos do Hprt1.

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L. granatensis G T A A C T C G G T T A G C C T ~ T C A T ~ ~ ~ C C ~ T T C ~ ~ ~ ~ ~ C C A G A ~ G C T T G T C C G A A C C G A G C C ~ C T G A C G G ~ A T C A A A C A A A G G A A A T T T A A G G G











Figura 7. Mapa de polimorfismos do Hprt1.

W

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J2

Sequences by SourceSequences by Source

Sequences by SourceSequences by Source

W

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J2Figura 7. Mapa de polimorfismos do Hprt1.

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L. granatensis G T A A C T C G G T T A G C C T ~ T C A T ~ ~ ~ C C ~ T T C ~ ~ ~ ~ ~ C C A G A ~ G C T T G T C C G A A C C G A G C C ~ C T G A C G G ~ A T C A A A C A A A G G A A A T T T A A G G G











Lepus granatensisLepus granatensis

Figura 5. Rede Median-Joining dos haplótipos do locus Hprt1 do cromosoma X do coelho europeu (Geraldes et al., 2006).

Haplotype NetworkHaplotype Network

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Versailles

Vaulx-en-Velin

Carlucet

Zaragoza

Perpignan

Castelló

Benavente

Zamora

La Rioja

Madrid

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Cuenca

Galicia

Bragança

Toledo

Ciudad Real

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Córdoba

Sevilha

Doñana

Vila Real

Idanha-a-nova

Vila Viçosa

Elvas

Figura 8. Distribuição geográfica dos conjuntos de haplótipos amostrados do Hprt1 do coelho europeu (adaptado de Geraldes et al., 2006).

WBJ1J2

Geographic LocationGeographic Location

Haplotypes:

Bayesian AnalysisBayesian Analysis

► Phylogenetic analysisPhylogenetic analysis► BEAST v1.4.6BEAST v1.4.6 ((Drummond A.J. & Rambaut A., 2006Drummond A.J. & Rambaut A., 2006))► MCMCMCMC (Monte Carlo Integration using Markov (Monte Carlo Integration using Markov

Chains)Chains)► A very large set of phylogenetic treesA very large set of phylogenetic trees conditioned on a given datasetconditioned on a given dataset that relies on a simple division of the sequence data that relies on a simple division of the sequence data

into intervals unaffected by the proposed junctions into intervals unaffected by the proposed junctions

RecombinationRecombination Hot Spot Hot Spot (rHotSpot)(rHotSpot)

?

?

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BbR1wR1bR2bR2w

= coded as missing data?

All

= sets of sequences

Junction Junction Hot SpotHot Spot (jHotSpot) (jHotSpot)

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All

= set of sequences

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= monophyletic set of sequences

Info (Wj)+Info(Bj) = Info (All)

?

JunctionJunction Hot Spot Hot Spot (jHotSpot) (jHotSpot)

No recombination (NoRec)No recombination (NoRec)

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= set of sequences

►HKYHKY (Hasegawa-Kishino Yano) (Hasegawa-Kishino Yano) substitution model substitution model

► ‘‘strict clock’strict clock’ model model with a with a fix mean rate fix mean rate ofof 2.25 x 10 2.25 x 10-9-9/site/year (Geraldes /site/year (Geraldes et al.et al., , 2006)2006)

►Yule speciation modelYule speciation model (prior distribution (prior distribution for topologies)for topologies)

Bayesian AnalysisBayesian Analysis

Hypothesis TestingHypothesis Testing► Bayes factor: compare posterior support for the competing

hipotheses represented by the models rHotSpot, jHotSpot and NoRec (Kass & Raftery, 1995)

► Ratio of marginal likelihoods or evidences

► Monte Carlo integration estimate

D é um alinhamento de sequências de DNAHk é uma hipótese acerca da sua segmentação

k é um vector de parâmetros do modelo kπ(k |Hk) é a distribuição de probabilidade a priori de k pr(D | k ,Hk) é a função de verosimilhança

{θ (i) : i = 1, …, m} é uma amostra da distribuição de probabilidade a posteriori de k

Results and Results and DiscussionDiscussion

SimulationsSimulations

► Length of chain: 25,000,000 generations► Burnin: 5,000,000 generations► Parameter values recorded every 100 generations -

> sample size from the posterior: 200,000 parameter vectors

► Tree topologies recorded every 5,000 generations -> sample size from the posterior: 4,000 topologies

How strongly does the data support a How strongly does the data support a recombination hot spot at the proposed recombination hot spot at the proposed

location?location?

Figura 9. Suporte marginal para as hipóteses NoRec e rHotSpot.-4550 -4525 -4500 -4475 -4450 -4425

Suporte Marginal

0.005

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0.015

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0.025

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Frequê ncia

kkkk HLogHDprLog ,

36Re, 105,1 cNorHotSpotB

6,1662 Re, cNorHotSpote BLog

Bayes Factor:

Very strong evidence against NoRec

NoRecrHotSpot

Is a jHotSpot a good explanation of the Is a jHotSpot a good explanation of the observations?observations?

-4550 -4525 -4500 -4475 -4450 -4425Suporte Marginal

0.005

0.01

0.015

0.02

0.025

0.03

0.035

Frequê ncia

kkkk HLogHDprLog ,

Bayes Factor:

Figura 10. Suporte marginal para as hipóteses NoRec e jHotSpot.

4,1652 Re, cNojHotSpote BLog

35Re, 103,8 cNojHotSpotB

Very strong evidence against NoRec

NoRecjHotSpot

Is a jHotSpot a good explanation of the Is a jHotSpot a good explanation of the observations?observations?

-4480 -4460 -4440 -4420Suporte Marginal

0.005

0.01

0.015

0.02

0.025

0.03

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Frequê ncia

kkkk HLogHDprLog ,

Bayes Factor:

Figura 11 – Suporte marginal para as hipóteses rHotSpot e jHotSpot.

22,12 , jHotSpotrHotSpote BLog

84,1, jHotSpotrHotSpotB

Evidence against jHotSpot: not worth more than a bare mention

rHotSpotjHotSpot

The most parsimonious hypothesis: two The most parsimonious hypothesis: two junction eventsjunction events

► Monophyly Monophyly J1w J1w J1bJ1b J2w J2w J2bJ2b

► tMRCA(J1w) tMRCA(J1w) ≈ ≈ tMRCA(J1b)tMRCA(J1b)


tMRCA(All)

tMRCA(Wj)

tMRCA(Bj)

tMRCA(J1w)EtMRCA(J1b)


J1w W J2w J1b B J2b

tanarg_L_baw1J01

22H__w2J3

51H__w1J01

72H__w1J5

6H__w1J4

6H__w1J11

71H__w1J2

5H__w1J3

5H__w1J6

7H__w1J7

01H__w2J4

82H__w1J1

3H__w1J9

32H__caw1J21

81H__cw1J8

31H__w2J2

51H__W8

9H__W9

9H__W7

52H_ _baW8

31H__W5

21H__W4

11H__cbW01

22H__W21

41H__W11

41H__W31

41H_ _dcW1

1H__dcW3

1H__dcW6

2H__dcW2

1H__w2J1

42H__bB21

81H__B2

12H__b1J11

71H__b1J6

7H__B01

62H__b1J01

72H__b2J4

82H__b2J1

42H__b2J2

51H__b2J3

51H__B5

4H__B6

4H__B1

8H__b1J7

01H__b1J5

6H__B8

4H__b1J21

81H__B4

4H__B3

4H_ _b1J2

5H__B9

4H__B7

4H__B41

02H__b1J9

32H__b1J3

5H__baB3

1H__b1J4

6H__b1J8

31H__baB1

1H__B11

61H_ _baB2

1H__baB6

2H__b1J1

3H__B21

91H__B31

91H_

500000 1106 1.5106 2106 2.5106 3106tMRCA

510-7

110-6

1.510-6

210-6

frequency

2106 3106 4106tMRCA

210-7

410-7

610-7

810-7

110-6

1.210-6

frequency

tMRCA (J1w)tMRCA (J1b)

tMRCA (J2b)tMRCA (J2w)

419 Kyr

1,62 Myr

2,13 Myr

1,04 Myr

Figura 12. Exemplo de uma filogenia típica gerada pelo BEAST de acordo com o modelo jHotSpot.

Figura 13. Distribuição marginal do tMRCA das sequências J2.Figura 14. Distribuição marginal do tMRCA das sequências J1.

Are we justified in rejecting the most Are we justified in rejecting the most parsimonious hypothesis?parsimonious hypothesis?

► Monophyly Monophyly J1w J1w J1bJ1b J2w J2w J2bJ2b



tMRCA(All)

tMRCA(Wj)

tMRCA(Bj)



J1w W J2w J1b B J2b

► J1b and J2w: rarely monophyletic: J1b and J2w: rarely monophyletic: insuficient information?insuficient information?


tanarg_L_baw1J01

22H__w2J3

51H__w1J01

72H__w1J5

6H__w1J4

6H__w1J11

71H__w1J2

5H__w1J3

5H__w1J6

7H__w1J7

01H__w2J4

82H__w1J1

3H__w1J9

32H__caw1J21

81H__cw1J8

31H__w2J2

51H__W8

9H__W9

9H__W7

52H_ _baW8

31H__W5

21H__W4

11H__cbW01

22H__W21

41H__W11

41H__W31

41H_ _dcW1

1H__dcW3

1H__dcW6

2H__dcW2

1H__w2J1

42H__bB21

81H__B2

12H__b1J11

71H__b1J6

7H__B01

62H__b1J01

72H__b2J4

82H__b2J1

42H__b2J2

51H__b2J3

51H__B5

4H__B6

4H__B1

8H__b1J7

01H__b1J5

6H__B8

4H__b1J21

81H__B4

4H__B3

4H_ _b1J2

5H__B9

4H__B7

4H__B41

02H__b1J9

32H__b1J3

5H__baB3

1H__b1J4

6H__b1J8

31H__baB1

1H__B11

61H_ _baB2

1H__baB6

2H__b1J1

3H__B21

91H__B31

91H_

► Simulate jHotSpot with monophyly constraints over J1w, J1b, J2w and Simulate jHotSpot with monophyly constraints over J1w, J1b, J2w and J2bJ2b

Figura 12. Exemplo de uma filogenia típica gerada pelo BEAST de acordo com o modelo jHotSpot.


-4480 -4460 -4440 -4420

Suporte marginal

0.005

0.01

0.015

0.02

0.025

0.03

0.035

Frequê ncia

kkkk HLogHDprLog ,

Bayes Factor:

Figura 15. Suporte marginal para a hipótese jHotSpot com e sem imposição de monofilia para J1w, J1b, J2w e J2b

01,02 , jHotSpotBjHotSpotAe BLog

01,1, jHotSpotBjHotSpotAB

Evidence against any of the two models: not worth more than a bare mention

without monophyly constraints over J1w, J1b, J2w e J2bWith monophyly constraints over J1w, J1b, J2w e J2b

What phylogenetic inference can we make about What phylogenetic inference can we make about contact times between B and W clades?contact times between B and W clades?

► tMRCA(J1W) and tMRCA(J2b) probably correspond better to the true chronology of J1 and J2

► J1 and J2 precede the LGM► J1 (less geographically

restricted descendents) is much older than J2 (more geographically restricted descendents)

500000 1106 1.5106 2106Anos

510-7

110-6

1.510-6

210-6

Frequê ncia

428 Kyr

213 Kyr tMRCA(J2b)tMRCA(J2w)

1106 1.5106 2106 2.5106Anos

2.510-7

510-7

7.510-7

110-6

1.25 10-6

1.510-6

Frequê ncia

969 Kyr

702 Kyr tMRCA(J1b)tMRCA(J1w)

ConclusionsConclusions► We developed a new methodology to test, in a Bayesian framework,

the occurrence of Fisher’s junctions in recombinant DNA sequences► Hypotheses were tested by

simulating a very large set of phylogenetic trees conditioned on a given dataset that relies on a simple division of the sequence data into intervals unaffected by the proposed junctions

and comparing between their posterior support

► The test was applied with success to a set of DNA sequences of locus Hprt1 of the X chromosome of the European Rabbit, presenting strong evidences of the occurrence of Fisher’s junctions

► And allowed us to gain some inference about the chronology and geography of contact between the two subspecies of the European Rabbit

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