Moving up the hierarchy: A hypothesis on the evolution of a genetic sex determination pathway

Abstract

A hypothesis on the evolutionary origin of the genetic pathway of sex determination in the nematode Caenorhabditis elegans is presented here. It is suggested that the pathway arose in steps, driven by frequency-dependent selection for the minority sex at each step, and involving the sequential acquisition of dominant negative, neomorphic genetic switches, each one reversing the action of the previous one. A central implication is that the genetic pathway evolved in reverse order from the final step in the hierarchy up to the first. The possible applicability of the model to the other well-characterized sex determination pathway, that of Drosophila melanogaster, and to sex determination in mammals, is discussed, along with some potential implications for pathway evolution in general. Finally, the specific molecular and population genetic questions that the model raises are described and some tests are proposed.

The ends of a continuum: genetic and temperature‐dependent sex determination in reptiles

“…A tendency for increasing conservatism in the genes as we progress down the differentiation cascade (27,28) suggests that candidate genes higher up in the chain of influence are more likely to be involved in the sex-determining switch mechanism. Genes conserved across vertebrates that have been implicated in sex reversal, or that exhibit dose dependency, are obvious candidates.…”

“…(20,21) Implicit in this perspective is that differences in the mechanisms between the two modes are complex, (22) that they constitute a discrete dichotomous process, and that through appropriate experimental approaches, one can be demonstrated to the exclusion of the other. (21) Pieau, (23) reflecting that proposed for insects, (24) offered an alternative view by suggesting that a common underlying sex-differentiation pathway implied that there were no clear boundaries between TSD and GSD and empirical evidence (25) and a broader taxonomic perspective led Wilkins (26)(27)(28) to suggest that it is probable that all sexdetermining systems have some genetic component. Recent research on the genes involved in sex differentiation in alligators and turtles with TSD, (29)(30)(31)(32) which demonstrates remarkable homology in structure, function and expression of the sex-differentiation genes of mammals and reptiles, lends considerable support to that view.…”

Sex determination: insights from the chicken

“…This has led to the long-standing belief that much of the underlying genetic pathway is also likely to be conserved, with essentially only the master switches at the top of the pathway being different in the different vertebrate groups. (2,3) However, comparative studies on sex determination in the chicken embryo have revealed both conserved and divergent elements. This review will describe insights being gained from the chicken embryo as a model for vertebrate sex determination.…”

Genetic basis of male sexual behavior

“…These genes are members of the DM-domain transcription factor family and are required for multiple diverse aspects of male development in worms, flies, and vertebrates (Raymond et al, 1998(Raymond et al, , 2000Zarkower, 2001;Matsuda et al, 2002). Their conservation across phyla in both structure and function is in contrast to the nonconservation of genes upstream of them in the sex-determination hierarchy (Hodgkin, 1992;Wilkins, 1995;Marín and Baker, 1998). This suggests that they might be descendants of the primordial sex-determination system, one based on a dominant, male-determining sex factor (Hodgkin, 1992;Wilkins, 1995;Zarkower, 2001).…”

“…Their conservation across phyla in both structure and function is in contrast to the nonconservation of genes upstream of them in the sex-determination hierarchy (Hodgkin, 1992;Wilkins, 1995;Marín and Baker, 1998). This suggests that they might be descendants of the primordial sex-determination system, one based on a dominant, male-determining sex factor (Hodgkin, 1992;Wilkins, 1995;Zarkower, 2001).…”