Genomic structure affects the expression and evolution of phenotypes via its effect on genomic function. One example is the presence of sex chromosomes and the development of the sexual phenotype. Multiple forces account for the evolution of genomic structure and function, some acting synergistically and some in an antagonistic manner, in a co-evolutionary process between genomic architecture and environmental effects at different time scales. Here I review the evolution of sex chromosomes and how they affect sex determination, sex ratios, sexual selection, and sexual conflict, at the same time that these phenomena influence the evolution of genome organization. Because of this reciprocal interaction, the need to correctly identify sex chromosome systems in order to understand the causes and consequences of their evolution is emphasized. Importantly, it is argued that the existence of taxa lacking sex chromosomes poses a challenge to current evolutionary models and a unique opportunity to test them empirically using reptiles as a model system.

Ahituv N, Prabhakar S, Rubin EM, Couronne O: Mapping cis-regulatory domains in the human genome using multi-species conservation of synteny. Hum Mol Genet 14:3057–3063 (2005).
Albert AYK, Otto SP: Sexual selection can resolve sex-linked sexual antagonism. Science 310:119–121 (2005).
Almeida-Toledo LF, Foresti F, Daniel MFZ, Toledo SA: Sex chromosome evolution in fish: The formation of the neo-y chromosome in Eigenmannia (Gymnotiformes). Chromosoma 109:197–200 (2000).
Alonzo SH, Sinervo B: The effect of sexually antagonistic selection on adaptive sex ratio allocation. Evol Ecol Res 9:1097–1117 (2007).
Ayala FJ, Coluzzi M: Chromosome speciation: Humans, drosophila, and mosquitoes. Proc Natl Acad Sci USA 102:6535–6542 (2005).
Bachtrog D: A dynamic view of sex chromosome evolution. Curr Opin Genet Dev 16:578–585 (2006).
Baird TA, Hranitz JM, Timanus DK, Schwartz AM: Behavioral attributes influence annual mating success more than morphological traits in male collared lizards. Behav Ecol 18:1146–1154 (2007).
Berry JF, Shine R: Sexual size dimorphism and sexual selection in turtles (order Testudines). Oecologia 44:185–191 (1980).
Bonduriansky R, Rowe L: Intralocus sexual conflict and the genetic architecture of sexually dimorphic traits in Prochyliza xanthostoma (Diptera: Piophilidae). Evolution 59:1965–1975 (2005).
Brana F: Sexual dimorphism in lacertid lizards: Male head increase vs female abdomen increase? Oikos 75:511–523 (1996).
Bull JJ: Evolution of Sex Determining Mechanisms (Benjamin/Cummings, Menlo Park, California 1983).
Bull JJ: Perspective on sex determination: past and future, in Valenzuela N, Lance VA (eds.): Temperature Dependent Sex Determination in Vertebrates, (Smithsonian Institution Press, Washington DC, 2004).
Bull JJ: Sex determination: Are two mechanisms better than one? J Biosci 33:5–8 (2008).
Bull JJ, Moon RG, Legler JM: Male heterogamety in kinosternid turtles (genus Staurotypus). Cytogenet Cell Genet 13:419–425 (1974).
Butler MA, Losos JB: Multivariate sexual dimorphism, sexual selection, and adaptation in greater antillean Anolis lizards. Ecological Monographs 72:541–559 (2002).
Calsbeek R, Bonneaud C: Postcopulatory fertilization bias as a form of cryptic sexual selection. Evolution 62:1137–1148 (2008).
Carr JL, Bickham JW: Sex-chromosomes of the Asian black pond turtle, Siebenrockiella crassicollis (Testudines, Emydidae). Cytogenet Cell Genet 31:178–183 (1981).
Carvalho AB, Clark AG: Y chromosome of D. pseudoobscura is not homologous to the ancestral Drosophila Y. Science 307:108–110 (2005).
Charlesworth B: The evolution of sex chromosomes. Science 251:1030–1033 (1991).
Charlesworth B: The evolution of chromosomal sex determination and dosage compensation. Curr Biol 6:149–162 (1996).
Charlesworth D: Plant sex determination and sex chromosomes. Heredity 88:94–101 (2002).
Charlesworth B, Charlesworth D: The degeneration of y chromosomes. Phil Transact Royal Soc London Series B Biol Sci 355:1563–1572 (2000).
Charlesworth B, Coyne JA, Barton NH: The relative rates of evolution of sex-chromosomes and autosomes. Am Nat 130:113–146 (1987).
Charlesworth D, Charlesworth B, Marais G: Steps in the evolution of heteromorphic sex chromosomes. Heredity 95:118–128 (2005).
Charnier M: Action de la temperature sur la sex-ratio chez l’embryon d’Agama agama (Agamidae, lacertilien). C R Séances Soc Biol Ouest Afr 160:620–622 (1966).
Charnov EL, Bull JJ: When is sex environmentally determined? Nature 266:828–830 (1977).
Charnov EL, Bull JJ: Non-fisherian sex ratios with sex change and environmental sex determination. Nature 338:148–150 (1989).
Coghlan A, Eichler EE, Oliver SG, Paterson AH, Stein L: Chromosome evolution in eukaryotes: A multi-kingdom perspective. Trends Genet 21:673–682 (2005).
Cole CJ, Gans C: Chromosomes of Bipes mesobaena and other amphisbaenians (Reptilia) with comments on their evolution. Am Mus Novit 2869:1–9 (1987).
Connallon T, Jakubowski E: Association between sex ratio distortion and sexually antagonistic fitness consequences of female choice. Evolution 63:2179–2183 (2009).
Cox RM, Butler MA, John-Alder HB: The evolution of sexual size dimorphism in reptiles, in Fairbairn DJ, Blanckenhorn WU, Szekely T (eds): Sex, Size and Gender Roles: Evolutionary Studies of Sexual Size Dimorphism (Oxford University Press, Oxford, UK 2007).
Cox RM, Stenquist DS, Calsbeek R: Testosterone, growth and the evolution of sexual size dimorphism. J Evol Biol 22:1586–1598 (2009).
Crews D, Moore MC: Historical contributions of research on reptiles to behavioral neuroendocrinology. Horm Behav 48:384–394 (2005).
Deeming DC: Prevalence of TSD in Crocodilians, in Valenzuela N, Lance VA (eds): Temperature Dependent Sex Determination in Vertebrates, pp 33–41 (Smithsonian Books, Washington DC, 2004).
Edwards SV, Kingan SB, Calkins JD, Balakrishnan CN, Jennings WB, Swanson WJ, Sorenson MD: Speciation in birds: Genes, geography, and sexual selection. Proc Natl Acad Sci USA 102:6550–6557 (2005).
Engelstadter J: Muller’s ratchet and the degeneration of Y chromosomes: A simulation study. Genetics 180:957–967 (2008).
Ernst CH, Barbour RW: Turtles of the World. (Smithsonian Institution Press, Washington DC, 1989).
Ewert MA, Jackson DR, Nelson CE: Patterns of temperature-dependent sex determination in turtles. J Exp Zool 270:3–15 (1994).
Ewert MA, Etchberger CR, Nelson CE: Turtle sex determining modes and TSD patterns, and some TSD pattern correlates, in Valenzuela N, Lance VA (eds): Temperature Dependent Sex Determination in Vertebrates, pp 21– 32 (Smithsonian Books, Washington DC, 2004).
Ezaz T, Quinn AE, Miura I, Sarre SD, Georges A, Graves JAM: The dragon lizard Pogona vitticeps has ZZ/ZW micro-sex chromosomes. Chromosome Res 13:763–776 (2005).
Ezaz T, Valenzuela N, Grutzner F, Miura I, Georges A, Burke RL, Graves JAM: An XX/XY sex microchromosome system in a freshwater turtle, Chelodina longicollis (Testudines: Chelidae) with genetic sex determination. Chromosome Res 14:139–150 (2006).
Fisher RA: The Genetical Theory of Natural Selection. (Oxford University Press, Oxford, UK 1930).
Fitze PS, Le Galliard JF: Operational sex ratio, sexual conflict and the intensity of sexual selection. Ecol Letters 11:432–439 (2008).
Fraser JA, Heitman J: Chromosomal sex-determining regions in animals, plants and fungi. Curr Opin Genet Dev 15:645–651 (2005).
Georges A, Ezaz T, Quinn AE, Sarre SD: Are reptiles predisposed to temperature-dependent sex determination? Sex Dev DOI: 10.1159/000279441 (2010).
Gibbons JW, Lovich JE: Sexual dimorphism in turtles with emphasis on the slider turtle (Trachemys scripta). Herpetol Monogr 4:1–29 (1990).
Gorelick R: Theory for why dioecious plants have equal length sex chromosomes. Am J Bot 92:979–984 (2005).
Graves JAM: The rise and fall of SRY. Trends Genet 18:259–264 (2002).
Graves JAM: Sex chromosome specialization and degeneration in mammals. Cell 124:901–914 (2006).
Gray SM, McKinnon JS: Linking color polymorphism maintenance and speciation. Trends Ecol Evol 22:71–79 (2007).
Grutzner F, Rens W, Tsend-Ayush E, El-Mogharbel N, O’Brien PCM, et al: In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes. Nature 432:913–917 (2004).
Harlow PS: Temperature-dependent sex determination in lizards, in Valenzuela N, Lance VA (eds.): Temperature Dependent Sex Determination in Vertebrates, (Smithsonian Books, Washington DC, 2004).
Head G, May RM, Pendleton L: Environmental determination of sex in the reptiles. Nature 329:198–199 (1987).
Henning F, Trifonov V, Ferguson-Smith MA, de Almeida-Toledo LF: Non-homologous sex chromosomes in two species of the genus Eigenmannia (Teleostei: Gymnotiformes). Cytogenet Genome Res 121:55–58 (2008).
Hood ME, Antonovics J, Koskella B: Shared forces of sex chromosome evolution in haploid-mating and diploid-mating organisms: Microbotryum violaceum and other model organisms. Genetics 168:141–146 (2004).
Husak JF, Fox SF: Sexual selection on locomotor performance. Evol Ecol Res 10:213–228 (2008).
Irschick DJ, Meyers JJ, Husak JF, Le Galliard JF: How does selection operate on whole-organism functional performance capacities? A review and synthesis. Evol Ecol Res 10:177–196 (2008).
Jaenike J: Sex chromosome meiotic drive. Ann Rev Ecol Syst 32:25–49 (2001).
Janes DE, Organ C, Valenzuela N: New resources inform study of genome size, content and organization in non-avian reptiles. Integr Comp Biol 48:447–453 (2008).
Janzen FJ, Krenz JG: Phylogenetics: Which was first, TSD or GSD?, in Valenzuela N, Lance VA (eds): Temperature Dependent Sex Determination in Vertebrates, pp 121–130 (Smithsonian Books, Washington DC, 2004).
Just W, Baumstark A, Sub A, Graphodatsky A, Rens W, et al: Ellobius lutescens: Sex determination and sex chromosome. Sex Dev 1:211–221 (2007).
Kawai A, Nishida-Umehara C, Ishijima J, Tsuda Y, Ota H, Matsuda Y: Different origins of bird and reptile sex chromosomes inferred from comparative mapping of chicken Z-linked genes. Cytogenet Genome Res 117:92–102 (2007).
King RB, Jadin RC, Grue M, Walley HD: Behavioural correlates with hemipenis morphology in new world natricine snakes. Biol J Linnean Soc 98:110–120 (2009).
Kirkpatrick M, Hall DW: Sexual selection and sex linkage. Evolution 58:683–691 (2004a).
Kirkpatrick M, Hall DW: Male-biased mutation, sex linkage, and the rate of adaptive evolution. Evolution 58:437–440 (2004b).
Kitano J, Ross JA, Mori S, Kume M, Jones FC, et al: A role for a neo-sex chromosome in stickleback speciation. Nature 461:1079–1083 (2009).
Kral J: Evolution of multiple sex chromosomes in the spider genus Malthonica (Araneae: Agelenidae) indicates unique structure of the spider sex chromosome systems. Chromosome Res 15:863–879 (2007).
Lan TY, Chen RY, Li XL, Dong FP, Qi YC, Song WQ: Microdissection and painting of the W chromosome in Ginkgo biloba showed different labelling patterns. Bot Studies 49:33–37 (2008).
Lewis KR, John B: Chromosome Marker (Little Brown, Boston 1963).
Lindholm A, Breden F: Sex chromosomes and sexual selection in poeciliid fishes. Am Nat 160:S214–S224 (2002).
Liu ZY, Moore PH, Ma H, Ackerman CM, Ragiba M, et al: A primitive Y chromosome in papaya marks incipient sex chromosome evolution. Nature 427:348–352 (2004).
Mank JE: The evolution of sexually selected traits and antagonistic androgen expression in actinopterygiian fishes. Am Nat 169:142–149 (2007).
Mank JE: The W, X, Y and Z of sex-chromosome dosage compensation. Trends Genet 25:226–233 (2009).
Mank JE, Ellegren H: Parallel divergence and degradation of the avian W sex chromosome. Trends Ecol Evol 22:389–391 (2007).
Mank JE, Ellegren H: Sex-linkage of sexually antagonistic genes is predicted by female, but not male, effects in birds. Evolution 63:1464–1472 (2009a).
Mank JE, Ellegren H: Are sex-biased genes more dispensable? Biol Letters 5:409–412 (2009b).
Martinez P, Valenzuela N, Georges A, Graves JAM: An XX/XY heteromorphic sex chromosome system in the Australian chelid turtle Emydura macquarii, a new piece in the puzzle of sex chromosome evolution in turtles. Chromosome Res 16:815–825 (2008).
Masly JP, Jones CD, Noor MAF, Locke J, Orr HA: Gene transposition as a cause of hybrid sterility in Drosophila. Science 313:1448–1450 (2006).
Matsuda Y, Nishida-Umehara C, Tarui H, Kuroiwa A, Yamada K, et al: Highly conserved linkage homology between birds and turtles: bird and turtle chromosomes are precise counterparts of each other. Chromosome Res 13:601–615 (2005).
Matsunaga S, Kawano S: Sex determination by sex chromosomes in dioecious plants. Plant Biol 3:481–488 (2001).
McBee K, Bickham JW, Rhodin AGJ, Mittermeier RA: Karyotypic variation in the genus Platemys (Testudines, Pleurodira). Copeia 1985:445–449 (1985).
Miles DB, Sinervo B, Hazard LC, Svensson EI, Costa D: Relating endocrinology, physiology and behaviour using species with alternative mating strategies. Funct Ecol 21:653–665 (2007).
Miller PM, Gavrilets S, Rice WR: Sexual conflict via maternal-effect genes in ZW species. Science 312:73 (2006).
Ming R, Moore PH: Genomics of sex chromosomes. Curr Opin Plant Biol 10:123–130 (2007).
Ming R, Yu QY, Moore PH: Sex determination in papaya. Semin Cell Dev Biol 18:401–408 (2007).
Modi WS, Crews D: Sex chromosomes and sex determination in reptiles – commentary. Curr Opin Genet Dev 15:660–665 (2005).
Morbey YE, Ydenberg RC: Protandrous arrival timing to breeding areas: A review. Ecol Letters 4:663–673 (2001).
Nakamura M: Sex determination in amphibians. Semin Cell Dev Biol 20:271–282 (2009).
Nei M: Accumulation of nonfunctional genes on sheltered chromosomes. Am Nat 104:311–322 (1970).
Nelson NJ, Cree A, Thompson MB, Keall SN, Daugherty CH: Temperature-dependent sex determination in tuatara, in Valenzuela N, Lance VA (eds): Temperature Dependent Sex Determination in Vertebrates, pp 53–58 (Smithsonian Books, Washington DC, 2004).
Ohno S: Sex Chromosomes and Sex-Linked Genes. (Springer-Verlag, Berlin 1967).
Organ CL, Janes DE: Evolution of sex chromosomes in Sauropsida. Integr Comp Biol 48:512–519 (2008).
Patel NH: Evolutionary biology: Time, space and genomes. Nature 431:28–29 (2004).
Pearse DE, Avise JC: Turtle mating systems: Behavior, sperm storage, and genetic paternity. J Heredity 92:206–211 (2001).
Peichel CL, Ross JA, Matson CK, Dickson M, Grimwood J, et al: The master sex-determination locus in threespine sticklebacks is on a nascent Y chromosome. Curr Biol 14:1416–1424 (2004).
Pieau C: Sur la proportion sexuelle chez les embryons de deux chéloniens (Testudo graeca L. and Emys orbicularis L.) issues d’oeufs incubés articifiellement. C R Hebdom Sciences Acad Scie Serie D 272:3071–3074 (1971).
Pigozzi MI, Solari AJ: The ZW pairs of two paleognath birds from two orders show transitional stages of sex chromosome differentiation. Chromosome Res 7:541–551 (1999).
Pires-DaSilva A: Evolution of the control of sexual identity in nematodes. Semin Cell Dev Biol 18:362–370 (2007).
Place AR, Lance VA: The temperature-dependent sex determination drama – same cast, different stars, in Valenzuela N, Lance VA (eds): Temperature Dependent Sex Determination in Vertebrates, pp 99–110 (Smithsonian Books, Washington DC, 2004).
Pokorna M, Kratochvil L: Phylogeny of sex-determining mechanisms in squamate reptiles: Are sex chromosomes an evolutionary trap? Zool J Linnean Soc 156:168–183 (2009).
Poschadel JR, Meyer-Lucht Y, Plath M: Response to chemical cues from conspecifics reflects male mating preference for large females and avoidance of large competitors in the European pond turtle, Emys orbicularis. Behaviour 143:569–587 (2006).
Quinn AE, Georges A, Sarre SD, Guarino F, Ezaz T, Graves JAM: Temperature sex reversal implies sex gene dosage in a reptile. Science 316:411 (2007).
Reeve HK, Pfennig DW: Genetic biases for showy males: are some genetic systems especially conducive to sexual selection? Proc Natl Acad Sci USA 100:1089–1094 (2003).
Rice WR: Sex chromosomes and the evolution of sexual dimorphism. Evolution 38:735–742 (1984).
Rice WR: The accumulation of sexually antagonistic genes as a selective agent promoting the evolution of reduced recombination between primitive sex-chromosomes. Evolution 41:911–914 (1987).
Rice WR: Sexually antagonistic genes – experimental-evidence. Science 256:1436–1439 (1992).
Rice WR: Evolution of the Y sex chromosome in animals. Bioscience 46:331–343 (1996).
Rice WR, Gavrilets S, Friberg U: Sexually antagonistic ‘zygotic drive’ of the sex chromosomes. PloS Genet 4:e1000313 (2008).
Richards S, Liu Y, Bettencourt BR, Hradecky P, Letovsky S, et al: Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution. Genome Res 15:1–18 (2005).
Roldan ERS, Gomendio M: The Y chromosome as a battle ground for sexual selection. Trends Ecol Evol 14:58–62 (1999).
Saether SA, Saetre GP, Borge T, Wiley C, Svedin N, et al: Sex chromosome-linked species recognition and evolution of reproductive isolation in flycatchers. Science 318:95–97 (2007).
Sakata JT, Crews D: Developmental sculpting of social phenotype and plasticity. Neuroscie Biobehav Rev 28:95–112 (2004).
Sarre SD, Georges A, Quinn A: The ends of a continuum: Genetic and temperature-dependent sex determination in reptiles. Bioessays 26:639–645 (2004).
Sato M, Ikeda M: Chromosomal complements of two forms of Neanthes japonica (Polychaeta, Nereididae) with evidence of male-heterogametic sex-chromosomes. Mar Biol 112:299–307 (1992).
Schmid M, Feichtinger W, Steinlein C, Garcia RV, Badillo AF: Chromosome banding in amphibia – XXVIII. Homomorphic XY sex chromosomes and a derived Y-autosome translocation in Eleutherodactylus riveroi (Anura, Leptodactylidae). Cytogenet Genome Res 101:62–73 (2003).
Sharma GP, Kaur P, Nakhasi U: Female heterogamety in the Indian cryptodiran chelonian, Kachuga smithi Gray, in Tiwari KK, Srivistava CB (eds): Dr BS Chuahah Commemoration Volume, pp 359–368 (Zoological Society of India, Orissa, India 1975).
Shine R: Reproductive strategies in snakes. Proc Royal Soc London Series B Biol Sci 270:995–1004 (2003).
Sites JWJ, Bickham JW, Haiduk MW, Iverson JB: Banded karyotypes of six taxa of kinosternid turtles. Copeia 1979:692–698 (1979).
Solari AJ: Sex Chromosomes and Sex Determination in Vertebrates (CRC Press Inc., Boca Raton, Florida 1994).
Stephens PR, Wiens JJ: Evolution of sexual size dimorphisms in emydid turtles: ecological dimorphism, Rensch’s rule, and sympatric divergence. Evolution 63:910–925 (2008).
Uller T: Sex-specific sibling interactions and offspring fitness in vertebrates: Patterns and implications for maternal sex ratios. Biol Rev 81:207–217 (2006).
Uller T, Olsson M: Multiple paternity in reptiles: Patterns and processes. Mol Ecol 17:2566–2580 (2008).
Valenzuela N: Temperature-dependent sex determination, in Deeming DC (ed): Reptilian Incubation: Environment and Behaviour, pp 211–227 (Nottingham University Press, Nottingham, UK 2004a).
Valenzuela N: Evolution and maintenance of temperature-dependent sex determination, in Valenzuela N, Lance VA (eds): Temperature Dependent Sex Determination in Vertebrates, pp 131–147 (Smithsonian Books, Washington DC, 2004b).
Valenzuela N: Sexual development and the evolution of sex determination. Sex Dev 2:64–72 (2008a).
Valenzuela N: Evolution of the gene network underlying gonadogenesis in turtles with temperature-dependent and genotypic sex determination. Integr Comp Biol 48:476–485 (2008b).
Valenzuela N: The painted turtle, Chrysemys picta: A model system for vertebrate evolution, ecology, and human health. CHS Protocols DOI: 10.1101/pdb.emo124.
Valenzuela N, Lance VA: Temperature Dependent Sex Determination in Vertebrates. (Smithsonian Books, Washington DC, 2004).
Valenzuela N, Adams DC, Janzen FJ: Pattern does not equal process: exactly when is sex environmentally determined? Am Nat 161:676–683 (2003).
Vallender EJ, Lahn BT: How mammalian sex chromosomes acquired their peculiar gene content. Bioessays 26:159–169 (2004).
Vallender EJ, Lahn BT: Multiple independent origins of sex chromosomes in amniotes. Proc Natl Acad Sci USA 103:18031–18032 (2006).
Van Damme R, Entin P, Vanhooydonck B, Herrel A: Causes of sexual dimorphism in performance traits: A comparative approach. Evol Ecol Res 10:229–250 (2008).
Van Doorn GS, Kirkpatrick M: Turnover of sex chromosomes induced by sexual conflict. Nature 449:909–912 (2007).
van Doorn GS: Intralocus sexual conflict. Ann N Y Acad Sci 1168:52–71 (2009).
Volff JN, Schartl M: Variability of genetic sex determination in poeciliid fishes. Genetica 111:101–110 (2001).
Waters PD, Wallis MC, Graves JAM: Mammalian sex – origin and evolution of the Y chromosome and SRY. Semin Cell Dev Biol 18:389–400 (2007).
Werren JH, Beukeboom LW: Sex determination, sex ratios, and genetic conflict. Annu Rev Ecol Syst 29:233–261 (1998).
White MJD: Models of speciation. Science 159:1065–1070 (1968).
Wiens JJ: Widespread loss of sexually selected traits: How the peacock lost its spots. Trends Ecol Evol 16:517–523 (2001).
Wikelski M, Trillmich F: Body size and sexual size dimorphism in marine iguanas fluctuate as a result of opposing natural and sexual selection: An island comparison. Evolution 51:922–936 (1997).
Woolley SC, Sakata JT, Crews D: Evolutionary insights into the regulation of courtship behavior in male amphibians and reptiles. Physiol Behav 83:347–360 (2004).
Yin T, DiFazio SP, Gunter LE, Zhang X, Sewell MM, et al: Genome structure and emerging evidence of an incipient sex chromosome in Populus. Genome Res 18:422–430 (2008).
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