The origin of the ability to generate novelty is one of the main mysteries in evolution. Pioneers of evolutionary theory, including Baldwin 
, Simpson 
, and Waddington 
, suggested how useful novelty might be enhanced by physiological adaptations and by the robustness of the developmental process. These early theories were limited by a lack of knowledge of the molecular mechanisms of development.
Recent decades saw breakthroughs in the depth of understanding of molecular and developmental biology. Many of these findings were unified in the theory of facilitated variation 
, presented by Kirschner and Gerhart, that addresses the following question: how can small, random genetic changes be converted into complex useful innovations? In order to understand novelty in evolution, Kirschner and Gerhart integrated observations on molecular mechanisms to show how the current design of an organism helps to determine the nature and the degree of future variation. The key observation is that the organism, by its intrinsic construction, biases both the type and the amount of its phenotypic variation in response to random genetic mutation 
. In other words, the organism seems to be built in such a way that small genetic mutations have a high chance of yielding a large phenotypic payoff.
To understand FV, it is important to compare it to the related concept of evolvability. A biological system is evolvable if it can readily acquire novel functions through genetic changes that help the organism survive and reproduce in future environments 
. Evolvability is composed of two aspects: 1) variability: the capacity to generate new phenotypes 2) fitness: the fitness of the new phenotypes in future environments. Most studies of evolvability focused on the first aspect, variability. Such studies measured the range and diversity of the phenotypic variation that can be generated by a given mutation, usually without discerning between potentially useful phenotypes and non-useful ones 
(for an interesting exception see Ciliberti et al 
). FV theory adds to previous considerations by focusing on the nature of the generated variation, and specifically on the organism's ability to generate novel phenotypes which are potentially useful
Facilitated variation (FV) is made possible by certain features of biological design. One of these is the existence of ‘weak regulatory linkage’ 
, where general and non-instructive signals can trigger large pre-prepared responses. For example, changes in growth hormone concentration at a localized position (limb bud in an embryo) can trigger large useful changes in the shape of the limb, driven by the conserved mechanisms for growth of bones, muscles, blood vessels, and nerves 
. A good example is the ease of changing beak shapes with any of many possible mutations that affect the concentration of a single morphogenic factor 
(). In weak regulatory linkage, the information about the output is pre-built into the regulated system without instruction from the regulator, which only selects between states. Such regulatory organization reduces the constraints for evolving new regulations and for generating complex potentially useful phenotypes.
A small number of mutations evokes large useful phenotypic adaptation in systems showing facilitated variation.
An additional feature that is important for FV is modular design 
, seen for example, in the highly conserved body-plan of the embryo 
and in the compartmental organization of gene regulation and signaling networks 
. Modularity helps to relieve the concern that a mutation might interfere with many different parts of the organism. With properly designed modularity, variation within each module can be generated without harming other modules 
Facilitated variation can be in principle studied experimentally, for example by generating mutants and scanning the types of phenotypes generated. For example, a study on mutants of the lac
regulatory region indicated that the shape of the gene input function is channeled in directions of AND-like and OR-like functions, rather than other possibilities 
An open question is how does FV spontaneously evolve? It is not clear how selection in a present environment can lead to designs that increase the probability of useful changes in future environments. How does evolutionary theory account for the emergence of special designs that make it easy to generate novel and useful variation?
The key point in our study is the observation that environments in nature do not vary randomly, but rather seem to have common rules or regularities 
. Specifically, environmental goals faced by organisms or molecules may be thought of as composed of a combination of subgoals 
. When environments change, the organisms encounter a new goal that is still made of the same or similar subgoals. For example, on the level of the organism, the same subgoals, such as digesting food, avoiding predation, and reproducing, must be fulfilled in each new environment but with different nuances and combinations. On the level of cells, the same subgoals such as adhesion and signaling must be fulfilled in each tissue type but with different input and output signals. On the level of proteins, the same subgoals, such as enzymatic activity, binding to other proteins, regulatory input domains, etc., are shared by many proteins but with different combinations in each case.
One may thus propose that in many cases, the different possible environments share a language of modularity, in the sense that they are all made of certain combinations of a set of subgoals. We thus test the possibility that under such patterned varying environments, the organism can learn over many generations the language common to the environments encountered in its past. We ask whether FV arises in such systematically varying environments, by measuring the ability of simple model systems to adapt to new, previously unseen goals, which are in the same language as past goals.
We employ two well-studied model systems: combinatorial logic circuits 
and RNA secondary structure 
. We find that the standard experiment of setting a goal which remains constant over time leads to highly optimized systems that show little FV. In contrast, FV is readily generated under modularly varying goals (MVG), in which goals change over time but share the same subgoals 
. We find that MVG evolution enhances the ability to generate novel phenotypes as long as novelty is modular: phenotypes with novel modules or novel combinations of modules. We show that organisms under MVG store information about past goals in their genomes, and evolve weak linkage that allows small genetic changes to unleash large phenotypic responses that do not ruin the modular structure of the organism. Our study thus suggests that environments that change in a systematic fashion promote the evolution of facilitated variation, and leave an imprint on the evolvability properties of the organisms, allowing them to generalize to new conditions that are in the same language as past conditions.