Journal Article

Melanocortin 4 receptor mutations contribute to the adaptation of cavefish to nutrient-poor conditions

Aspiras, A.C., Rohner, N., Martineau, B., Borowsky, R.L. and Tabin, C.J.

Record Number:
2897
Year:
2015
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Pages:
9668-9673
Volume:
112
Abstract:
Despite recent advances in the understanding of morphological evolution, the genetic underpinnings of behavioral and physiological evolution remain largely unknown. Here, we study the metabolic changes that evolved in independently derived populations of the Mexican cavefish, Astyanax mexicanus. A hallmark of cave environments is scarcity of food. Cavefish populations rely almost entirely on sporadic food input from outside of the caves. To survive under these conditions, cavefish have evolved a range of adaptations, including starvation resistance and binge eating when food becomes available. The use of these adaptive strategies differs among independently derived cave populations. Although all cavefish populations tested lose weight more slowly than their surface conspecifics during restricted rations, only a subset of cavefish populations consume more food than their surface counterparts. A candidate gene-based screen led to the identification of coding mutations in conserved residues of the melanocortin 4 receptor (MC4R) gene, contributing to the insatiable appetite found in some populations of cavefish. Intriguingly, one of the mutated residues has been shown to be linked to obesity in humans. We demonstrate that the allele results in both reduced maximal response and reduced basal activity of the receptor in vitro. We further validate in vivo that the mutated allele contributes to elevated appetite, growth, and starvation resistance. The allele appears to be fixed in cave populations in which the overeating phenotype is present. The presence of the same allele in multiple caves appears to be due to selection from standing genetic variation present in surface populations.
Times Cited:
1
Related Records:
Hubbs, C.L. and Innes, W.T. (1936)Gresser, E. B. and Breder, C. M. (1940)Bridges, W. (1940)Breder, C. M. and Gresser, E. B. (1941)Breder, C. M. and Gresser, E. B. (1941)Breder, C. M. and Gresser, E. B. (1941)Breder, C. M. (1942)Breder, C. M. (1943)Breder, C. M. (1943)Osorio Tafall, B. F. (1943)Breder, C. M. (1944)Alvarez, J. (1946)Alvarez, J. (1947)Breder, C. M. and Rasquin, P. (1947)Breder, C. M. and Rasquin, P. (1947)Schlagel, S. R. and Breder, C. M. (1947)Rasquin, P. (1949)Luling, K. H. (1953)Luling, K. H. (1953)Luling, K. H. (1953)Stefanelli, A. (1954)Rasquin, P. and Rosenbloom, L. (1954)Stefanelli, A. (1954)Thines, G. (1954)Luling, K. H. (1954)Luling, K. H. (1954)Luling, K. H. (1955)Luling, K. H. (1955)Sadoglu, P. (1956)Sadoglu, P. (1957)Sadoglu, P. (1957)Thines, G. and Kahling, J. (1957)Grobbel, G. and Hahn, G. (1958)Cahn, P. H. (1958)Kahling, J. (1961)Luling, K. H. (1962)Burgers, A. C. J., Bennink, P. J. H. and van Oordt, G. J. (1963)Franck, A. (1964)Boucquey, C., Thines, G. and Van Der Borght, C. (1965)Thines, G., Wolff-Van Ermengem, F., Boucquey, C. and Soffie, M. (1965)Cavicchioli, G. and Guarnieri, P. (1966)Reed, M. (1966)Thines, G., Soffie, M. and Vandenbussche, E. (1966)Peters, N. and Peters, G. (1966)Carmignani, M. P. A. (1966)Sadoglu, P. (1967)Schemmel, C. (1967)Pfeiffer, W. (1967)Walters, V. and Liu, R. K. (1967)Pfeiffer, W. (1967)Popper, A. N. and Tavolga, W. N. (1967)Carmignani, M. P. A. (1968)Wilkens, H. (1968)Mattheij, J. A. (1968)Mattheij, J. A. (1968)Sadoglu, P. and McKee, A. (1969)Mattheij, J. A. (1969)Weiss, B. A. (1969)Mattheij, J. A. and Sprangers, J. A. P. (1969)Whitt, G. S. and Maeda, F. S. (1970)Wilkens, H. (1970)Wilkens, H. (1970)Wilkens, H. (1970)Gertychowa, R. (1970)Gertychowa, R. (1970)Mattheij, J. A. (1970)Popper, A. N. (1970)Mattheij, J. A. (1970)Weiss, B. and Martini, J. (1970)Wiley, S. and Mitchell, R. W. (1971)Wiley, S. and Mitchell, R. W. (1971)Wilkens, H. (1971)Gertychowa, R. (1971)Zaccone, G. (1971)Popper, A. N. (1971)Avise, J. C. and Selander, R. K. (1972)Wilkens, H. (1972)Wilkens, H. (1972)Wilkens, H. (1972)Zaccone, G. (1972)Thines, G. and Wissocq, N. (1972)Wilkens, H. and Burns, R. J. (1972)Yasuda, K. (1973)Mitchell, R. W. (1973)Durand, J. P. (1973)Thines, G. and LeGrain, J. M. (1973)Zeitlin, S. M. (1973)Zeitlin, S. M. and McDevitt, D. S. (1973)Schemmel, C. (1973)Voneida, T. J. (1973)Chakraborty, R. and Nei, M. (1974)Schemmel, C. (1974)Schemmel, C. (1974)Sligar, C. (1974)Omura, Y. (1975)Sadoglu, P. (1975)Peters, N., Scholl, A. and Wilkens, H. (1975)Wilkens, H. (1976)Durand, J. P. (1976)Herwig, H. J. (1976)Erckens, W. and Weber, F. (1976)Herwig, H. J. (1976)Voneida, T. J. and Sligar, C. (1976)Sligar, C. and Voneida, T. J. (1976)Kirby, R. F., Thompson, K. W. and Hubbs, C. (1977)Yew, D. T. and Yoshihara, H. M. (1977)Wilkens, H. (1977)Mitchell, R. W., Russell, W. H. and Elliott, W. R. (1977)Zaccone, G. (1977)Durand, J. P. (1978)Thines, G. and Weyers, M. (1978)Durand, J. P. (1979)Sadoglu, P. (1979)Wilkens, H., Peters, H. and Schemmel, C. (1979)Woodhead, A. D. and Achey, P. M. (1979)Quinn, T. P. (1980)Wilkens, H. (1980)Wilkens, H. (1980)Schemmel, C. (1980)Weissert, R. (1980)Reddell, J. R. (1981)Herwig, H. J. (1981)Campenhausen, C., Riess, I. and Weissert, R. (1981)Weissert, R. and Campenhausen, C. (1981)Lamprecht, G. and Weber, F. (1982)Tabata, M. (1982)Rose, F. L. and Mitchell, R. W. (1982)Erckens, W. and Martin, W. (1982)Erckens, W. and Martin, W. (1982)Jankowska, M. and Thines, G. (1982)Romero, A. (1983)Parzefall, J. (1983)Zilles, K., Tillmann, B. and Bennemann, R. (1983)Romero, A. (1984)Romero, A. (1984)Wilkens, H. (1984)Voneida, T. J. and Fish, S. E. (1984)Schuppa, M. (1984)Lamprecht, G. and Weber, F. (1985)Romero, A. (1985)Teyke, T. (1985)Wilkens, H. (1985)Burchards, H., Dolle, A. and Parzefall, J. (1985)De Fraipont, M. (1986)Fraipont, M. (1986)De Fraipont, M. and Thines, G. (1986)De Fraipont, M. and Thines, G. (1986)Romero, A. (1986)Hassan, E. S. (1986)Wilkens, H. (1986)Parzefall, J. (1986)Wilkens, H. and Huppop, K. (1986)Huppop, K. (1986)De Fraipont, M. (1987)De Fraipont, M. (1987)Wilkens, H. (1987)Huppop, K. (1987)De Fraipont, M. (1988)Fricke, D. (1988)Teyke, T. (1988)Wilkens, H. (1988)Huppop, K. (1988)Langecker, T. G. (1989)Fricke, D. and Parzefall, J. (1989)Teyke, T. (1989)Hassan, E. S. (1989)Fack, H. and Wilkens, H. (1989)Huppop, K. (1989)Abdel-Latif, H., Hassan, E. S. and von Campenhausen, C. (1990)Klimpel, B. and Parzefall, J. (1990)Langecker, T. G. (1990)Yokoyama, R. and Yokoyama, S. (1990)Yokoyama, R and Yokoyama, S (1990)Teyke, T. (1990)Parzefall, J. and Fricke, D. (1990)Peters, N., Schmidt, W. and Fricke, D. (1990)Riedel, G. and Krug, L. (1991)Langecker, T. G., Wilkens, H. and Junge, P. (1991)Parzefall, J. and Fricke, D. (1991)Huppop, K. and Wilkens, H. (1991)Huppop, K. (1991)Campenhausen, C. (1991)Lamprecht, G. and Weber, F. (1992)De Fraipont, M. (1992)Langecker, T. G. and Longley, G. (1992)Hassan, E. S., Abdel-Latif, H. and Biebricher, R. (1992)Parzefall, J. (1992)Parzefall, J. (1992)Wilkens, H. (1992)Wilkens, H. and Meyer, M. (1992)Langecker, T. G. (1993)Langecker, T. G., Schmale, H. and Wilkens, H. (1993)Langecker, T. G., Schmale, H. and Wilkens, H. (1993)Parzefall, J. (1993)Hoffman, S. and Hausberg, C. (1993)Peters, N., Schacht, V., Schmidt, W. and Wilkens, H. (1993)Borowsky, R. (1994)Teyke, T. and Schaerer, S. (1994)Langecker, T. G., Neumann, B., Hausberg, C. and Parzefall, J. (1995)Yokoyama, S., Meany, A., Wilkens, H. and Yokoyama, R. (1995)Langecker, T. G., Wilkens, H. and Schmale, H. (1995)Borowsky, R. (1996)Riedel, G. (1997)Behrens, M., Langecker, T.G., Wilkens, H. and Schmale, H. (1997)Riedel, G. and Krug, L. (1997)Borowsky, R. and Espinasa, L. (1997)Behrens, M, Wilkens, H and Schmale, H (1998)Contreras-Balderas, S. and Lozano-Vilano, M.D.L. (1998)Wilkens, H. (1998)Jeffery, WR and Martasian, DP (1998)Kullander, S. O. (1999)Baker, CF and Montgomery, J (1999)Jeffery, W. R., Strickler, A.G., Guiney, S., Heyser, D.G. and Tomarev, S.I. (2000)Ford, D.C. (2000)Espinasa, L. and Borowsky, R. (2000)Yamamoto, Y. and Jeffery, W. R. (2000)Strickler, A.G., Yamamoto, Y. and Jeffery, W. R. (2001)Montgomery, J.C., Coombs, S. and Baker, C.F. (2001)Boudriot, F and Reutter, K (2001)Espinasa, L. and Borowsky, R. (2001)Jeffery, W. R. (2001)Berg, A. and Watson, G.M. (2002)Strickler, AG, Famuditimi, K and Jeffery, WR (2002)Romero, A., Jeffery, W.R. and Yamamoto, Y. (2002)Dowling, TE, Martasian, DP and Jeffery, WR (2002)Borowsky, RL and Wilkens, H (2002)Krejca, J. (2002)Contreras-Balderas, S, Almada-Villela, P, Lozano-Vilano, M de L and Garcia-Ramirez, ME (2003)Strecker, U. (2003)Strecker, U., Bernatchez, L. and Wilkens, H. (2003)Porter, M.L. and Crandall, K.A. (2003)Sarma, SSS, Lopez-Romulo, A and Nandini, S (2003)Wilkens, H. and Strecker, U. (2003)McCauley, DW, Hixon, E and Jeffery, WR (2004)Protas ME, Hersey C, Kochanek D, Zhou Y, Wilkens H, Jeffery WR, Zon LI, Borowsky R, Tabin CJ. (2006)Protas, M., Conrad, M., Gross, J.B., Tabin, C. and Borowsky, R.L. (2007)Salin, K, Voituron, Y, Colson, C and Hervant, F (2008)Protas, M, Tabansky, I, Conrad, M, Gross, JB, Vidal, O, Tabin, C and Borowsky, RL (2008)Gross, J.B., Protas, M., Conrad, M., Scheid, P.E., Vidal, O., Jeffery, W.R., Tabin, C. and others (2008)Jeffery, WR (2009)Kowalko, J, Gross, JB, Protas, M, Borowsky, RL and Tabin, C (2009)Salin, K., Voituron, Y., Mourin, J. and Hervant, F. (2010)Yamamoto, Y. and Jeffery, W.R. (2011)Kish, P.E., Bohnsack, B.L., Gallina, D., Kasprick, D.S. and Kahana, A. (2011)Esquivel-Bobadilla, S (2011)Kowalko, J, Rohner, N, Borowsky, RL and Tabin, C (2011)Salin, K, Voituron, Y, Mourin, J and Hervant, F (2011)Bradic, M, Beerli, P and Borowsky, RL (2011)Protas, M. and Jeffery, W. R. (2012)Idda, M.L., Bertolucci, C., Vallone, D., Gothilf, Y., Sánchez-Vázquez, F.J. and Foulkes N.S. (2012)Wilkens, H. (2012)Trontelj, P. (2012)Dufton, M, Hall, BK and Franz-Odendaal, T. (2012)Jeffery, W.R. (2012)Gross, J.B. (2012)Hervant, F. (2012)Bradic, M., Beerli, P., Garcia-de Leon, F. J., Esquivel-Bobadilla, S. and Borowsky, R. L. (2012)Kowalko, J., Rohner, N., Linden, T.A., Rompani S.B., Warren, W.C., Borowsky, R., Tabin, C.J., Jeffery, W.R. and Yoshizawa M. (2013)Bradic, M., Teotonio, H. and Borowsky, R. L. (2013)Gross, J.B., Furterer, A., Carlson, B.M. and Stahl, B.A. (2013)Stahl, B. A. and Gross, J. B. (2013)Pennisi, E. (2013)Stahl, AL (2013)Pazza, R (2013)Bibliowicz, J., Alie, A., Espinasa, L., Yoshizawa, M., Blin, M., Hinaux, H., Legendre, L., Pere, S. and Retaux, S. (2013)Atukorala, A. D. S., Hammer, C., Dufton, M. and Franz-Odendaal, T. A. (2013)Beale, A., Guibal, C., Tamai, T. K., Klotz, L., Cowen, S., Peyric, E., Reynoso, V. H., Yamamoto, Y. and Whitmore, D. (2013)Beale, A. (2013)Elliott, William R. (2013)Kowalko, J.E., Rohner, N., Rompani, S.B., Peterson, B.K., Linden, T.A., Yoshizawa, M., Kay, E.H., Weber, J., Hoekstra, H.E., Jeffery, W.R., Borowsky, R. and Tabin, C.J. (2013)Rohner, N., Jarosz, D.F., Kowalko, J.E., Yoshizawa, M., Jeffery, W.R., Borowsky, R.L., Lindquist, S. and Tabin, C.J. (2013)Rohner, N (2013)Gross, J.B., Krutzler, A.J. and Carlson, B.M. (2014)Holzman, R., Perkol-Finkel, S. and Zilman, G. (2014)Atukorallaya, D. and Franz-Odendaal, T. (2014)Espinasa, L., Bartolo, N.D. and Newkirk, C.E. (2014)Atukorala, A. D. S. and Franz-Odendaal, T. A. (2014)McGaugh, S.E., Gross, J.B., Aken, B., Blin, M., Borowsky, R., Chalopin, D., Hinaux, H., Jeffery, W.R., Keene, A., Ma, L., Minx, P., Murphy, D., O'Quin, K.E., Retaux, S., Rohner, N., Searl, S.M., Stahl, B.A., Tabin, C., Volff, J.N., Yoshizawa M, Warren WC. (2014)Moran, D., Softley, R. and Warrant, E.J. (2014)Elliott, W.R. (2014)Caballero-Hernandez, O., Hernandez-Patricio, M., Sigala-Regalado, I., Morales-Malacara, J. B. and Miranda-Anaya, M. (2015)Riddle, M and Tobin, C. J. (2015)Aspiras, A.C., Rohner, N., Martineau, B., Borowsky, R.L. and Tabin, C.J. (2015)Bradic, M, Rohner, N, Tabin, C and Borowsky, R. (2015)Stahl, Bethany A. and Gross, Joshua B. (2015)Rohner, N (2015)Stahl, B. A., Ma, L and Gross, J. B. (2015)Yoshizawa, Masato, Robinson, Beatriz G., Duboue, Erik R., Masek, Pavel, Jaggard, James B., O'Quin, Kelly E., Borowsky, Richard L., Jeffery, William R. and Keene, Alex C. (2015)Stemmer, M., Schuhmacher, L.-N., Foulkes, N.S., Bertolucci, C. and Wittbrodt, J. (2015)Jaggard, J. B. (2015)O'Quin, Kelly E., Doshi, Pooja, Lyon, Anastasia, Hoenemeyer, Emma, Yoshizawa, Masato and Jeffery, William R. (2015)Devos, Lucie, Alie, A. and Retaux, S (2015)Carlson, B.M., Onusko, S.W. and Gross, J.B. (2015)McGaugh, S. E. (2015)Dufton, Megan and Franz-Odendaal, Tamara A. (2015)Silva, D. M. Z. A., Utsunomia, R., Pansonato-Alves, J.C., Oliveira, C. and Foresti, F. (2015)Moran, D., Softley, R. and Warrant, E.J. (2015)Hinaux, H., Blin, M., Fumey, J., Legendre, L., Heuze, A., Casane, D. and Retaux, S. (2015)Fumey, J. (2015)Pennisi, E. (2016)Pennisi, E (2016)Rohner, Nicolas (2016)Yoshizawa, M., Settle, A., Macaspac, C., Fernandes, V. Yoshida, M. and Keene, A. (2016)Gross, J.B., Stahl, B.A., Powers, A.K. and Carlson, B.M. (2016)Aspiras, A., Tabin, C. and Rohner, N. (2016)Foulkes, N. S., Whitmore, D., Vallone, D and Bertolucci, C. (2016)Keene, A.C., Yoshizawa, M. and McGaugh, S.E. (2016)Lyon, A., Krutzler, A.J., Gross, J.B. and O'Quin, K.E. (2016)O'Quin, K.E., Doshi, P., Lyon, A., Hoenemeyer, E., Yoshizawa, M. and Jeffery, W.R. (2016)Retaux, S., Alie, A., Blin, M., Devos, L., Elipot, Y. and Hinaux, H. (2016)Carlson, B.M. and Gross, J.B. (2016)Casane, D. and Retaux, S. (2016)O'Quin, Kelly and McGaugh, Suzanne E. (2016)Atukorala, A. D. S. and Franz-Odendaal, Tamara A. (2016)Beale, A. D. and Whitmore, D. (2016)Beale, A., Whitmore, D. and Moran, D. (2016)Schmitter-Soto, JJ (2016)Yoshizawa, M (2017)Riddle, M. R.; Tabin, C. J (2017)Jaggard, J. B., Robinson, B. G., Stahl, B, Oh, I, Masek, P, Yoshizawa, M and Keene, A. (2017)Krishnan, J and Rohner, N (2017)Stahl, B (2017)Alvarado, C.G. (2017)Stahl, B.A. and Gross, J.B. (2017)Jaggard, J. B. (2017)Wilkens, H. and Strecker, U. (2017)Torres-Paz, J (2017)Hinaux, H, Recher, G, Alie, A., Legendre, L, Blin, M. and Retaux, S (2017)Riddle, M (2017)Fumey J, Hinaux H, Noirot C, Thermes C, Re´ taux S, Casane D. (2017)Lyon, A., Powers, A. K., Gross, J. B. and O'Quin, K. E. (2017)Schmitter-Soto, JJ (2017)Gross, J. B. (2017)Riddle, M (2017)Kaplan, S.A., Powers, A.K. and Gross, J.B. (2017)Powers, A.K., Kaplan, S.A., Boggs, T.E. and Gross, J. (2018)Sovrano, V.A., Potrich, D., Foà, A. and Bertolucci, C. (2018)Carlson, B.M. and Gross, J.B. (2018)Espinasa, L. (2018)Sears, C.R. and Gross, J.B. (2018)Espinasa, L., Legendre, L., Fumey, J., Blin, M., Rétaux, S. and Espinasa, M. (2018)Stah, B.A., Sears, C.R., Ma, L., Perkins, M. and Gross, J.B. (2018)Mirande, J.M. (2018)Powers, A.K., Boggs, T.E. and Gross, J.B. (2018)Borowsky, R. (2018)Tabin, J.A., Aspiras, A., Martineau, B., Riddle, M., Kowalko, J. Borowsky, R. Rohner, N. and Tabin, C.J. (2018)Borowsky, R., Luk, A., He, X.J. and Kim, R.S. (2018)Yoshizawa, M., Settle, A., Hermosura, M.C., Tuttle, L.J., Cetraro, N., Passow, C.N. and McGaugh, S.E. (2018)Riddle, M.R., Boesmans, W., Caballero, O, Kazwiny, Y. and Tabin,C.J. (2018)Riddle, M.R., Aspiras, A.C., Gaudenz, K., Peuß, R., Sung, J.Y., Martineau, B., Peavey, M., Box, A.C., Tabin, J.A., McGaugh, S., Borowsky, R., Tabin, C.J. and Rohner, N. (2018)Fernandes, V.F.L., Macaspac, C., Lu, L. and Yoshizawa, M. (2018)Riddle, M., Martineau, B., Peavey, M. and Tabin, C. (2018)Rohner, N. (2018)Garita-Alvarado, C.A., Barluenga, M. and Ornelas-García, C.P. (2018)Lloyd, E., Olive, C., Stahl, B.A., Jaggarda, J.B., Amaral, P., Dubouéa, E.R and Keene, A.C. (2018)Pazza, R., Dergam, J.A. and Kavalco, K.F. (2018)Jaggard, J.B., Stahl, B.A., Lloyd, E., Prober, D.A., Duboue, E.R. and Keene, A.C. (2018)Kopp, J., Avasthi, S. and Espinasa, L. (2018)Kling, J. (2018)Ojha, A. and Watve, M. (2018)Torres-Paz,J., Hyacinthe, C., Pierre, C., Retaux, S. (2018)Chin, J.S.R., Gassant, C.E., Amaral, P.M., Lloyd, E., Stahl, B.A., Jaggard, J.B., Keene, A.C. and Duboue, E.R. (2018)Gore, A., Jeffery, W., Retaux, S. and Rohner, N. (2018)Gore, A.V., Rohner, N., Rétaux, S. and Jeffery, W.R. (2018)Stern, D.B and Crandall, K.A. (2018)Ma, L., Strickler, A.G., Parkhurst, A., Yoshizawa, M., Shi, J. and Jeffery, W.R. (2018)Carlson, B.M., Klingler, I.B., Meyer, B.J. and Gross, J.B. (2018)Alie, A., Devos, L., Torres-Paz, J., Prunier, L., Boulet, F., Blin, M., Elipot, Y. and Retaux, S. (2018)Xiong, S., Krishnan, J., Peuß, F. and Rohner, N. (2018)Ren, X.Y., Hamilton, N., Müller, F. and Yamamoto, Y. (2018)Klaassen, H., Wang, Y., Adamski, K., Rohner, N. and Kowalko, J.E. (2018)Elliott, W.R. (2018)Rohner, N. (2018)Devitsina, G.V. and Golovkina, T.V. (2018)Fumey, J., Hinaux, H., Noirot, C., Thermes, C., Rétaux, S. and Casane, D. (2018)Gross, J.B., Weagley, J., Stahl, B.A., Ma, L., Espinasa, L. and McGaugh, S.E. (2018)Frøland Steindal, I.V., Beale, A.D., Yamamoto, Y. and Whitmore, D. (2018)Devi, A., Atukorala, S. and Franz-Odendaal, T.A. (2018)Retaux, S. (2018)Blin, M., Tine, E., Meister, L., Elipot, Y., Bibliowicz, J., Espinasa, L. and Rétaux, S. (2018)Ornelas-García, P,. Pajares, S., Sosa-Jiménez, V.M., Rétaux, S. and Miranda-Gamboa, R.A. (2018)Pennisi, E. (2019)Stahl, B.A., Peuß, R., McDole, B., Kenzior, A., Jaggard, J.B., Gaudenz, K., Krishnan, J., McGaugh, S.E., Duboue, E.R., Keene, A.C and Rohner, N. (2019)Kindl, G.H. and O’Quin, K.E. (2019)Blin, M. and Retaux, S. (2019)