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)Bridges, W. (1940)Gresser, E. B. and Breder, C. M. (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)Breder, C. M. and Rasquin, P. (1947)Schlagel, S. R. and Breder, C. M. (1947)Alvarez, J. (1947)Breder, C. M. and Rasquin, P. (1947)Rasquin, P. (1949)Luling, K. H. (1953)Luling, K. H. (1953)Luling, K. H. (1953)Thines, G. (1954)Stefanelli, A. (1954)Rasquin, P. and Rosenbloom, L. (1954)Luling, K. H. (1954)Luling, K. H. (1954)Stefanelli, A. (1954)Luling, K. H. (1955)Luling, K. H. (1955)Sadoglu, P. (1956)Sadoglu, P. (1957)Thines, G. and Kahling, J. (1957)Sadoglu, P. (1957)Cahn, P. H. (1958)Grobbel, G. and Hahn, G. (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)Thines, G., Wolff-Van Ermengem, F., Boucquey, C. and Soffie, M. (1965)Boucquey, C., Thines, G. and Van Der Borght, C. (1965)Carmignani, M. P. A. (1966)Peters, N. and Peters, G. (1966)Thines, G., Soffie, M. and Vandenbussche, E. (1966)Cavicchioli, G. and Guarnieri, P. (1966)Reed, M. (1966)Sadoglu, P. (1967)Schemmel, C. (1967)Pfeiffer, W. (1967)Pfeiffer, W. (1967)Popper, A. N. and Tavolga, W. N. (1967)Walters, V. and Liu, R. K. (1967)Carmignani, M. P. A. (1968)Wilkens, H. (1968)Mattheij, J. A. (1968)Mattheij, J. A. (1968)Mattheij, J. A. and Sprangers, J. A. P. (1969)Sadoglu, P. and McKee, A. (1969)Weiss, B. A. (1969)Mattheij, J. A. (1969)Mattheij, J. A. (1970)Mattheij, J. A. (1970)Popper, A. N. (1970)Gertychowa, R. (1970)Gertychowa, R. (1970)Weiss, B. and Martini, J. (1970)Whitt, G. S. and Maeda, F. S. (1970)Wilkens, H. (1970)Wilkens, H. (1970)Wilkens, H. (1970)Popper, A. N. (1971)Gertychowa, R. (1971)Wiley, S. and Mitchell, R. W. (1971)Wiley, S. and Mitchell, R. W. (1971)Wilkens, H. (1971)Zaccone, G. (1971)Wilkens, H. and Burns, R. J. (1972)Thines, G. and Wissocq, N. (1972)Avise, J. C. and Selander, R. K. (1972)Wilkens, H. (1972)Wilkens, H. (1972)Wilkens, H. (1972)Zaccone, G. (1972)Zeitlin, S. M. (1973)Zeitlin, S. M. and McDevitt, D. S. (1973)Thines, G. and LeGrain, J. M. (1973)Schemmel, C. (1973)Voneida, T. J. (1973)Durand, J. P. (1973)Yasuda, K. (1973)Mitchell, R. W. (1973)Schemmel, C. (1974)Schemmel, C. (1974)Chakraborty, R. and Nei, M. (1974)Sligar, C. (1974)Sadoglu, P. (1975)Peters, N., Scholl, A. and Wilkens, H. (1975)Omura, Y. (1975)Voneida, T. J. and Sligar, C. (1976)Sligar, C. and Voneida, T. J. (1976)Herwig, H. J. (1976)Durand, J. P. (1976)Herwig, H. J. (1976)Erckens, W. and Weber, F. (1976)Wilkens, H. (1976)Wilkens, H. (1977)Zaccone, G. (1977)Kirby, R. F., Thompson, K. W. and Hubbs, C. (1977)Yew, D. T. and Yoshihara, H. M. (1977)Mitchell, R. W., Russell, W. H. and Elliott, W. R. (1977)Thines, G. and Weyers, M. (1978)Durand, J. P. (1978)Sadoglu, P. (1979)Wilkens, H., Peters, H. and Schemmel, C. (1979)Woodhead, A. D. and Achey, P. M. (1979)Durand, J. P. (1979)Wilkens, H. (1980)Wilkens, H. (1980)Schemmel, C. (1980)Quinn, T. P. (1980)Weissert, R. (1980)Campenhausen, C., Riess, I. and Weissert, R. (1981)Reddell, J. R. (1981)Weissert, R. and Campenhausen, C. (1981)Herwig, H. J. (1981)Jankowska, M. and Thines, G. (1982)Lamprecht, G. and Weber, F. (1982)Erckens, W. and Martin, W. (1982)Erckens, W. and Martin, W. (1982)Rose, F. L. and Mitchell, R. W. (1982)Tabata, M. (1982)Parzefall, J. (1983)Zilles, K., Tillmann, B. and Bennemann, R. (1983)Romero, A. (1983)Wilkens, H. (1984)Voneida, T. J. and Fish, S. E. (1984)Schuppa, M. (1984)Romero, A. (1984)Romero, A. (1984)Teyke, T. (1985)Burchards, H., Dolle, A. and Parzefall, J. (1985)Wilkens, H. (1985)Lamprecht, G. and Weber, F. (1985)Romero, A. (1985)Parzefall, J. (1986)Wilkens, H. (1986)Wilkens, H. and Huppop, K. (1986)De Fraipont, M. (1986)Fraipont, M. (1986)De Fraipont, M. and Thines, G. (1986)Hassan, E. S. (1986)De Fraipont, M. and Thines, G. (1986)Huppop, K. (1986)Romero, A. (1986)Wilkens, H. (1987)De Fraipont, M. (1987)De Fraipont, M. (1987)Huppop, K. (1987)Teyke, T. (1988)Wilkens, H. (1988)Fricke, D. (1988)De Fraipont, M. (1988)Huppop, K. (1988)Teyke, T. (1989)Langecker, T. G. (1989)Fricke, D. and Parzefall, J. (1989)Hassan, E. S. (1989)Huppop, K. (1989)Fack, H. and Wilkens, H. (1989)Teyke, T. (1990)Parzefall, J. and Fricke, D. (1990)Klimpel, B. and Parzefall, J. (1990)Peters, N., Schmidt, W. and Fricke, D. (1990)Abdel-Latif, H., Hassan, E. S. and von Campenhausen, C. (1990)Langecker, T. G. (1990)Yokoyama, R. and Yokoyama, S. (1990)Yokoyama, R and Yokoyama, S (1990)Huppop, K. (1991)Campenhausen, C. (1991)Parzefall, J. and Fricke, D. (1991)Langecker, T. G., Wilkens, H. and Junge, P. (1991)Riedel, G. and Krug, L. (1991)Huppop, K. and Wilkens, H. (1991)Parzefall, J. (1992)Parzefall, J. (1992)Wilkens, H. (1992)Lamprecht, G. and Weber, F. (1992)Wilkens, H. and Meyer, M. (1992)Langecker, T. G. and Longley, G. (1992)De Fraipont, M. (1992)Hassan, E. S., Abdel-Latif, H. and Biebricher, R. (1992)Parzefall, J. (1993)Peters, N., Schacht, V., Schmidt, W. and Wilkens, H. (1993)Langecker, T. G. (1993)Langecker, T. G., Schmale, H. and Wilkens, H. (1993)Langecker, T. G., Schmale, H. and Wilkens, H. (1993)Hoffman, S. and Hausberg, C. (1993)Teyke, T. and Schaerer, S. (1994)Borowsky, R. (1994)Langecker, T. G., Neumann, B., Hausberg, C. and Parzefall, J. (1995)Langecker, T. G., Wilkens, H. and Schmale, H. (1995)Yokoyama, S., Meany, A., Wilkens, H. and Yokoyama, R. (1995)Borowsky, R. (1996)Behrens, M., Langecker, T. G., Wilkens, H. and Schmale, H. (1997)Riedel, G. (1997)Riedel, G. and Krug, L. (1997)Borowsky, R. and Espinasa, L. (1997)Jeffery, WR and Martasian, DP (1998)Wilkens, H. (1998)Contreras-Balderas, S. and Lozano-Vilano, M.D.L. (1998)Behrens, M, Wilkens, H and Schmale, H (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)Yamamoto, Y. and Jeffery, W. R. (2000)Espinasa, L. and Borowsky, R. (2000)Ford, D.C. (2000)Jeffery, W. R. (2001)Boudriot, F and Reutter, K (2001)Montgomery, J.C., Coombs, S. and Baker, C.F. (2001)Strickler, A.G., Yamamoto, Y. and Jeffery, W. R. (2001)Espinasa, L. and Borowsky, R. (2001)Krejca, J. (2002)Berg, A and Watson, GM (2002)Dowling, TE, Martasian, DP and Jeffery, WR (2002)Romero, A., Jeffery, W.R. and Yamamoto, Y. (2002)Borowsky, RL and Wilkens, H (2002)Strickler, AG, Famuditimi, K and Jeffery, WR (2002)Sarma, SSS, Lopez-Romulo, A and Nandini, S (2003)Porter, M.L. and Crandall, K.A. (2003)Contreras-Balderas, S, Almada-Villela, P, Lozano-Vilano, M de L and Garcia-Ramirez, ME (2003)Wilkens, H. and Strecker, U. (2003)Strecker, U. (2003)Strecker, U., Bernatchez, L. and Wilkens, H. (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)Protas, M, Tabansky, I, Conrad, M, Gross, JB, Vidal, O, Tabin, C and Borowsky, RL (2008)Gross, JB, Protas, M, Conrad, M, Scheid, PE, Vidal, O and others (2008)Jeffery, WR (2009)Kowalko, J, Gross, JB, Protas, M, Borowsky, RL and Tabin, C (2009)Kowalko, J, Rohner, N, Borowsky, RL and Tabin, C (2011)Bradic, M, Beerli, P and Borowsky, RL (2011)Esquivel-Bobadilla, S (2011)Wilkens, H. (2012)Trontelj, P. (2012)Jeffery, W.R. (2012)Protas, M. and Jeffery, W. R. (2012)Gross, J.B. (2012)Bradic, M., Beerli, P., Garcia-de Leon, F. J., Esquivel-Bobadilla, S. and Borowsky, R. L. (2012)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)Kowalko, J., Rohner, N., Linden, T.A., Rompani SB, Warren, W.C., Borowsky, R, Tabin, C.J., Jeffery, W.R. and Yoshizawa M. (2013)Gross, J.B., Furterer, A., Carlson, B.M. and Stahl, B.A. (2013)Elliott, William R. (2013)Stahl, B. A. and Gross, J. B. (2013)Stahl, AL (2013)Bradic, M., Teotonio, H. and Borowsky, R. L. (2013)Bibliowicz, J., Alie, A., Espinasa, L., Yoshizawa, M., Blin, M., Hinaux, H., Legendre, L., Pere, S. and Retaux, S. (2013)Pazza, R (2013)Moran, D, Softley, R and Warrant, EJ (2014)Espinasa, L., Bartolo, N.D. and Newkirk, C.E. (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)Elliott, W.R. (2014)Silva, D. M. Z. A., Utsunomia, R., Pansonato-Alves, J.C., Oliveira, C. and Foresti, F. (2015)Moran, D, Softley, R and Warrant, EJ (2015)Hinaux, Helene, Blin, Maryline, Fumey, Julien, Legendre, Laurent, Heuze, Aurelie, Casane, Didier and Retaux, Sylvie (2015)Fumey, J. (2015)McGaugh, S. E. (2015)Aspiras, A.C., Rohner, N., Martineau, B., Borowsky, R.L. and Tabin, C.J. (2015)Stahl, Bethany A. and Gross, Joshua B. (2015)Stahl, B. A., Ma, L and Gross, J. B. (2015)Caballero-Hernandez, O., Hernandez-Patricio, M., Sigala-Regalado, I., Morales-Malacara, J. B. and Miranda-Anaya, M. (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)Bradic, M, Rohner, N, Tabin, C and Borowsky, R. (2015)Jaggard, J. B. (2015)Rohner, N (2015)Devos, Lucie, Alie, A. and Retaux, S (2015)Keene, A.C., Yoshizawa, M. and McGaugh, S.E. (2016)Casane, D and Retaux, S (2016)Beale, A., Whitmore, D and Moran, D (2016)Schmitter-Soto, JJ (2016)O'Quin, Kelly and McGaugh, Suzanne E. (2016)Gross, J.B., Stahl, B.A., Powers, A.K. and Carlson, B.M. (2016)Rohner, Nicolas (2016)Aspiras, A., Tabin, C. and Rohner, N. (2016)Retaux, Sylvie, Alie, Alexandre, Blin, Maryline, Devos, Lucie, Elipot, Yannick and Hinaux, Helene (2016)Wilkens, H. and Strecker, U. (2017)Fumey J, Hinaux H, Noirot C, Thermes C, Re´ taux S, Casane D. (2017)Schmitter-Soto, JJ (2017)Jaggard, J. B., Robinson, B. G., Stahl, B, Oh, I, Masek, P, Yoshizawa, M and Keene, A. (2017)Stahl, B (2017)Stahl, B.A. and Gross, J.B. (2017)Jaggard, J. B. (2017)Krishnan, J and Rohner, N (2017)Alvarado, C.G. (2017)Hinaux, H, Recher, G, Alie, A., Legendre, L, Blin, M. and Retaux, S (2017)Pazza, R., Dergam, J.A. and Kavalco, K.F. (2018)Elliott, W.R. (2018)Devitsina, G.V. and Golovkina, T.V. (2018)Kling, J. (2018)Chin, J.S.R., Gassant, C.E., Amaral, P.M., Lloyd, E., Stahl, B.A., Jaggarda, J.B., Keenea, A.C. and Duboue, E.R. (2018)Fumey, J., Hinaux, H., Noirot, C., Thermes, C., Rétaux, S. and Casane, D. (2018)Stern, D.B and Crandall, K.A. (2018)Xiong, S., Krishnan, J., Peuß, F. and Rohner, N. (2018)Gross, J.B., Weagley, J., Stahl, B.A., Ma, L., Espinasa, L. and McGaugh, S.E. (2018)Espinasa, L. (2018)Espinasa, L., Legendre, L., Fumey, J., Blin, M., Rétaux, S. and Espinasa, M. (2018)Mirande, J.M. (2018)Borowsky, R. (2018)Jaggard, J.B., Stahl, B.A., Lloyd, E., Prober, D.A., Duboue, E.R. and Keene, A.C. (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)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)Rohner, N. (2018)Garita-Alvarado, C.A., Barluenga, M. and Ornelas-García, C.P. (2018)Alie, A., Devos, L., Torres-Paz, J., Prunier, L., Boulet, F., Blin, M., Elipot, Y. and Retaux, S. (2018)