A rearrangement is established as a barrier in parapatry. The accumulation of incompatibilites starts. Chrom 1. Rearranged

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1 Figure S1. An ancestral species splits in two according to the model discussed in Navarro and Barton (Evolution. In press. 2003). A rearrangement in chromosome 1 was involved in the process. From the moment at which the rearrangement establishes a barrier in parapatry until complete reproductive isolation has been achieved, positively selected changes that are incompatible between populations will accumulate preferentially if linked to the rearrangement. If speciation was recent, a comparison of K A /K S ratios between species A and B could disclose higher K A /K S values in chromosome 1 than in chromosome 2. A rearrangement is established as a barrier in parapatry. The accumulation of incompatibilites starts. Complete reproductive isolation is achieved. Divergence proceeds evenly in all chromosomes. Chrom 1. Rearranged Chrom 2. Colinear Ancestral Species Differential K A /K S Species A Species B 1

2 Table S1. K A and K S values in coding genes between human and chimpanzees, and their map position in the human genome. Locus Ref. Length Map pos Rearranged K A K S K A / K S (in bp) (in humans) Chrom. β-nerve growth factor p13.1 Yes Glucocerebrosidase (GBA) p21 Yes Urate oxidase p22 Yes IFI44 - p p31.1 Yes Rhesus-like protein p34-36 Yes Brain natriuretic protein p36.2 Yes Apolipoprotein AII q21-q23 Yes Involucrin q21 Yes RHBG q21.3 Yes L-selectin q23-25 Yes Complement receptor CR q32 Yes Decay Acelerating Factor DAF CD q32 Yes REN (Renin) q32 Yes Angiotensinogen q42-43 Yes Muscarine Acetylcholine Receptor M q43-44 Yes Mismatch Repair Gene MSH p22-21 Yes Histamine N-Methyltranferase q14-21 Yes Chemokine receptor q21 Yes β-1,3-galactosyltransferase q24-31 Yes Interleukin-8 receptor type A q35 Yes Interleukin-8 receptor type B q35 Yes hydroxy-tryptamine receptor 1F p12 No CC chemokine receptor p21 No G protein-coupled receptor STRL p21 No G protein-coupled receptor gpr q No Zinc finger protein q12-qter No AGTR q21-25 No α-2-hs-glycoprotein (AHSG) q27 No α-fetoprotein precursor q11-13 Yes Glycophorin-A q Yes hydroxy-tryptamine receptor 1A q11.2-q13 Yes Guanine nucleotide-binding q Yes regulatory protein-coupled receptor Interleukin q31.1 Yes Neuropeptide Y receptor Y q31.2 Yes Histamine H2 receptor q35 Yes AB0 Transporter Protein TAP p21.3 No Complement C p21.3 No Stress-activaded protein kinase 2A p No (CSBP) RhAG (Rh50 glycoprotein) p21.1-p11 No Stress-activated protein kinase p21.1 No T-cell receptor gv p15-p14 No T-cell receptor g p15-14 No GASZ q21.3 No Blue opsin q31.3-q32 No Leptin q31.3 No Muscarine Acetylcholine Receptor M q31-32 No Mitogen-activated protein kinase kinase q32 No (MAP2K1) Lipoprotein Lipase (LPL) p22 No DEFB1 (β-defensin 1) p No

3 DEFB2 (β-defensin 2) p No c-myc q No q24.13 AB0 Transferase q Yes α-γ-globin p15.5 No CD p15.5 No Dopamine D4 receptor p15.5 No ε-globin p15.5 No γ-globin p15.5 No NUDR p15.5 No Preproinsulin p15.5 No CD p12 Yes Atrophin-related protein DRPLA p13.31 Yes CD p13.2-p12.3 Yes Dombrock Glycoprotein p13-p12 Yes (ADP-ribosyltransferase 4) NKG2A (Killer Cell Lectin-like receptor) p13.2-p12.3 Yes NKG2E (Killer Cell Lectin-like receptor) p13.2-p12.3 Yes NKG2F (Killer Cell Lectin-like receptor) p13.2-p12.3 Yes Triosephosphate isomerase p13 Yes Interferon g q13.13 Yes Lysozyme q13.2 Yes Voltage-gated Na channel α subunit q13 Yes Melanin-concentrating hormone q23-24 Yes hydroxy-tryptamine receptor 2A q14-q21 No Angiogenin (RNAse 5) q No RNase k q11.1 No RNASE q11.1 No Homeobox protein OTX q21-q22 No OPTX q No Eosinophil cationic protein q24-31 No Eosinophil-derived neurotoxin q24-q31 No EPI q24.3 No Ig α heavy chain constant region q32.33 No Connexin q13.1 Yes β2-microglobin q21-q22.2 Yes Interleukin q26.1 Yes LCR16a p13.1 Yes Protamine P p13.3 Yes Protamine P p13.3 Yes TNP p13.3 Yes Cytochrome oxidase subunit q11 Yes Haptoglobin q22.1 Yes Melanocortin-1 receptor q24.3 Yes Elac p11.2 Yes Olfactory receptor p13.3 Yes BRCA q21 Yes Apolipoprotein H precursor (APO-H) q23 Yes DCP q23 Yes HGH (Human Growth Hormone) q24.2 Yes SoX q Yes Melanocortin-5 receptor p11.2 Yes CD p13.3 No Fut1-α(1,2)fucosyltransferase p13.3 No Fut3- α(1,3)fucosyltransferase p13.3 No Fut5- α(1,3)fucosyltransferase p13.3 No Fut6- α(1,3)fucosyltransferase p13.3 No

4 Apolipoprotein E q13.2 No Complement C5 α receptor q No Fut2- α(1,2)fucosyltransferase q13.3 No ILP q No ILT q13.4 No Low-affinity N-formyl peptide receptor q No N-formyl peptide receptor q No N-formyl peptide receptorlike q No UPAR, PLAUR Plasminogen activator q13 No urokinase receptor Prion protein p12 No α-a-crystalin q22.3 No Gene Bank 2 Chen and Li. Am. J. Hum Genet. 68, (2001) Chen et. al. The Journal of Heredity 92, (2001) 3 Eyre-Walker and Keightley Nature 397, (1999) 4

5 Table S2. Approximate cytological positions of the breakpoints of the chromosomal rearrangements differentiating humans and chimpanzees according to J.J.Yunis and O. Prakash (Science 215: , 1982). Chromosomes p breakpoint q breakpoint 1 p11 q11 2 tandem fusion 4 p14 q21 5 p13 q13 9 p13 q22 12 p12 q q13 16 p11 q12 17 p12 q q11 5