In the asymptotic limit of a large diffusivity ratio, certain two-component reaction-diffusion (RD) systems can admit localized spike solutions on a one-dimensional finite domain in a far-from-equilibrium nonlinear regime. It is known that two distinct bifurcation mechanisms can occur which generate spike patterns of increased spatial complexity as the domain half-length L slowly increases
so-called spike nucleation and spike self-replication. Self-replication is found to occur via the passage beyond a saddle-node bifurcation point that can be predicted through linearization around the inner spike profile. In contrast, spike nucleation occurs through slow passage beyond the saddle-node of a nonlinear boundary-value problem defined in the outer region away from the core of a spike. Here, by treating L as a static parameter under the Lagrangian framework, precise conditions are established within the semi-strong interaction asymptotic regime to determine which occurs, conditions that are confirmed by numerical simulation and continuation. For the Schnakenberg and Brusselator RD models, phase diagrams in parameter space are derived that predict whether spike self-replication or spike nucleation will occur first as L is increased, or whether no such instability will occur. For the Gierer-Meinhardt model with a non-trivial activator background, spike nucleation is shown to be the only possible spike-generating mechanism. From time-dependent PDE numerical results on an exponentially slowly growing domain, it is shown that the analytical thresholds derived from the asymptotic theory accurately predict critical values of L where either spike self-replication or spike-nucleation will occur. The global bifurcation mechanism for transitions to patterns of increased spatial complexity is further elucidated by superimposing time-dependent PDE simulation results on the numerically computed solution branches of spike equilibria in which L is the primary bifurcation parameter.