1 2 Holly Wichman Jim Bull 3 4 Phage Population Growth at 43° C A A* H B K ! X174 C G D E J F 5 6 7 8 9 10 Adaptation for cryptic coloration 11 12 Mouse coat color genetics Endothelin receptor B (piebald) mutation Genes Phenotypes Mouse Adamts20, Ectodysplasin-A (Eda), Endothelin 3 Human ligand (Edn3),Endothelin receptor B (Ednrb) Epidermal growth factor receptor (Egfr), Fibroblast growth factor receptor2 (Fgfr2), Inhibitor of kappaB kinase gamma (Ikbkg), C-kit receptor (kit), Ligand for c-kit receptor (kitl), Keratin complex 2, gene 17 (Krt2-17), LIM homeodomain protein 1 (Lmx1a), Mucolipin 3(Mcoln3), Pax-3 transcription factor (Pax3), Sideroflexin (Sfxn1), Neural crest transcription factor (Snai2), Sry-box containing gene 10 (Sox10), Sry-box containing gene 18 (Sox18), T- box 15 (tbx15), Growth factor (Wnt1), Growth factor (Wnt3a), Tyrosinase-related protein 2 (Tyrp2/Dct), Glycoprotein (Gpnmb), Membrane- assoc. transporter protein (Matp), Member of RAS oncogene family (Rab38), Silver protein (Pmel17), Tyrosinase (Tyr), Tyrosinas-related protein 1 (Tyrp1), Beta 3 subunit of adaptor protein 3 (Ap3b1), Delta subunit of adaptor protein 2 (Ap3d), Vacuoloar protein sorting 33a (Vps33a), Cno, Hermansky-Pudlak syndrome gene 1 (Hps1), Hermansky-Pudlak gene 3 (Hps3), Hermansky-Pudlak gene 4 (Hps4), Hermansky- Pudlak gene 5 (Hps5), Hermansky-Pudlak gene 6 (Hps6), Lysosomal trafficking regulator (Lyst), Ocular albinism type 1 (Oa1), Pallidin (Pldn), Rab geranylgeranyl transferase (Rabgtta), Melanophilin (Mlph), Myosin type Va (Myo5a), Myosin type 7a (Myo7a), RAS associated protein (Rab27a), Agouti signaling protein (Asip), Attractin (atrn), Gamma gluyltranspeptidase 1 (Ggt1), Melanocortin-1 receptor (Mc1r), E3 ubiquitin ligase (Mgrn1), Proopiomelanocortin (Pomc1), ATPase (Atp7a), ATPase (Atp7b), Excision repair deficiancy (Ercc) neutral mutation 13 14 Tyrosinase (albino) mutation Adaptive color polymorphism in rock pocket mice Mouse Human e s u o m habitat O’Neill Hills Pinacate Lava deleterious mutation 2 miles 15 16 Distribution of lava in the SouthWest Phenotypic variation in coat color Pinacates Kenzin Armendaris Carrizozo Pinacates Kenzin Armendaris Carrizozo Age (yrs) 1,700,000 530,000 760,000 1,000 Area (km2) 3500 142 435 329 17 18 Approach: Association studies Eumelanosome phenotype Agouti cAMP t = 1 pulse of agouti expression MSH Mc1r Phaeomelanosome t = 2 Light Dark t = 3 Coding Region 19 20 Mc1Mc1rr polymorphis miss in l igresponsibleht and dark C. intermedius from tforhe Pinac atmelanices color 0 1 2 2 2 3 3 3 4 4 4 6 6 6 7 7 8 9 9 5 2 0 4 9 1 2 2 7 8 9 3 5 9 2 8 1 1 2 Phenotype ID 2 6 5 3 8 3 4 5 8 1 5 3 1 9 0 7 9 5 7 C T C T G G C C C G C T T A T C C C C R R R R R R R R Dark 1371 T . T T . C . C . T . T T . C . C . Dark 1373 T . T T . C . C . T . T T . C . C . s l Dark 1374 T . T T . C . C . T . T T . C . C . a Dark 1375 T . T T . C . C . u T . T T . C . C . Dark 1376 T . T T . C . C . Perfect association between genotype and phenotype d T . T T . C . C . i Dark 1377 T . T T . C . C . v T . T T . C . C . i Mc1r DD Dark 1378 T . T T . C . C . d T . T T . C . C . Dark 1381 T . T T . C . C . n i T . T . T T . C C . Genotype: Mc1r locus Phenotype: coat color Dark 1383 T . T T . C . C . T . T T . C . C . Dark 1385 T . T T . C . C . T . T . T T . C . C . Dark 1386 T . T T . C . C . T . T T . C . C . * Complete Dark 1372 T . T T . C . C . Dark Dark 1379 T . T . T T . C . C . association . melanic Dark 1382 T . T T . C . C . holds for 102 Dark 1384 T . T . T T . C . C . Mc1r Dd . Dark 1412 T . T T . C . C . melanic and 73 . T . Dark 1416 T . T . T T . C . C . T . T . light individuals 1387 . G . T . Dark . G . T . 1402 . T . T . A . T . G . T . 1403 . 1404 . C A . G . T T . 1405 . G . T . A . T . G . T . 1406 . C . Light . C A . G . T T . Mc1r dd 1407 . G . T . 1408 . T . A . C . 1409 . A . T . G . T . 1410 . A . T . G . T . T 1411 . G . T . N = 202 individuals (404 alleles) . A . T . G . T . 1414 . G . T . 21 22 Amino acid mutations in the Mc1r receptor in rock pocket mice extracellular transmembrane intracellular 23 24 Distribution of Mc1r alleles in the Pinacates Arizona Arizona, USA Xmas 5km Tule lava West Mid East O'Neill Sonora, Mexico Substrate color: Coat color: Xmas Tule West Mid East O'Neill F.E.T. Amok Time Sample size: 6 85 7 5 45 77 = 225 P < 10-6 Dice 1947: Studied owl predation in deermice 25 26 Different allele frequency clines in Mc1r and mtDNA selected neutral e e p 1 c y f i e 1 f t c o o m i o y y n m k c r c e d n a n h 0.5 e d D e p 0.5 u u g r q c 1 q n e i c o e r n f r m a M l f a 0 e 0 m s e p 1 f f e 1 y l o o t e l o y y l l c c a p n n a e 0.5 D e 0.5 h u u r q q A 1 e e c N r r f f D M 0 0 t m l l l l i i t t e t s e t s d s e N d s i ’ e N i a ’ a Tule O W M Xmas E M Tule Xmas O E W Sampling locales Sampling locales 27.