Genetic assimilation is a process described byConrad H. Waddington by which aphenotype originally produced in response to an environmental condition, such as exposure to ateratogen, later becomes genetically encoded viaartificial selection ornatural selection. Despite superficial appearances, this does not require the (Lamarckian)inheritance of acquired characters, althoughepigenetic inheritance could potentially influence the result.[1] Waddington stated that genetic assimilation overcomes the barrier to selection imposed by what he calledcanalization of developmental pathways; he supposed that the organism's genetics evolved to ensure that development proceeded in a certain way regardless of normal environmental variations.
The classic example of genetic assimilation was a pair of experiments in 1942 and 1953 by Waddington. He exposedDrosophila fruit flyembryos toether, producing an extreme change in their phenotype: they developed a double thorax, resembling the effect of thebithorax gene. This is called ahomeotic change. Flies which developedhalteres (the modified hindwings oftrue flies, used for balance) with wing-like characteristics were chosen for breeding for 20 generations, by which point the phenotype could be seen without other treatment.[2]
Waddington's explanation has been controversial, and has been accused of being Lamarckian. More recent evidence appears to confirm the existence of genetic assimilation in evolution; in yeast, when astop codon is lost bymutation, thereading frame is preserved much more often than would be expected.[3] Genetic assimilation has been incorporated into theextended evolutionary synthesis.[4][5][6][7]
Conrad H. Waddington's classic experiment (1942) induced an extreme environmental reaction in the developing embryos ofDrosophila. In response toether vapor, a proportion of embryos developed a radicalphenotypic change, a secondthorax. At this point in the experimentbithorax is not innate; it is induced by an unusual environment. Waddington then repeatedly selectedDrosophila for thebithorax phenotype over some 20 generations. After this time, someDrosophila developedbithorax without the ether treatment.[8]
Waddington carried out a similar experiment in 1953, this time inducing thecross-veinlessphenocopy inDrosophila with a heat shock, with 40% of the flies showing the phenotype prior to selection. Again he selected for the phenotype over several generations, applying heat shock each time, and eventually the phenotype appeared even without heat shock.[9][10]
Waddington called the effect he had seen "genetic assimilation". His explanation was that it was caused by a process he called "canalization". He comparedembryonic development to a ball rolling down a slope in what he called anepigenetic landscape, where each point on the landscape is a possible state of the organism (involving many variables). As a particular pathway becomes entrenched or "canalized", it becomes more stable, likely to occur even in the face of environmental changes. Major perturbations such as ether or heat shock eject the developmental pathway from themetaphorical canal, exploring other parts of the epigenetic landscape. Selection in the presence of that perturbation leads to the evolution of a new canal; after the perturbation is discontinued, developmental trajectories continue to follow the canalized pathway.[10]
Other evolutionary biologists have agreed that assimilation occurs, but give a different, purelyquantitative genetics explanation in terms of Darwin'snatural orartificial selection. The phenotype, saycross-veinless, is presumed to be caused by a combination of multiple genes. The phenotype appears when the sum ofgene effects exceeds athreshold; if that threshold is lowered by a perturbation, say a heat shock, the phenotype is more likely to be seen. Continued selection under perturbing conditions increases thefrequency of the alleles of genes that promote the phenotype until the threshold is breached, and the phenotype appears without requiring the heat shock.[10][11]
Perturbations can be genetic or epigenetic rather than environmental. For example,Drosophila fruit flies have a heat shock protein,Hsp90, which protects the development of many structures in the adult fly from heat shock. If the protein is damaged by a mutation, then just as if it were damaged by the environmental effects of drugs, many different phenotypic variants appear; if these are selected for, they quickly establish without further need for the mutant Hsp90.[12]
In 2017, L. Fanti and colleagues replicated Waddington's experiments, but includedDNA sequencing, revealing that the wing phenotypes were due tomutational events, small deletions and the insertions oftransposable elements that were mobilised by the heat exposure.[13]
Waddington's theory of genetic assimilation was controversial.[4] Theevolutionary biologistsTheodosius Dobzhansky andErnst Mayr both thought that Waddington was using genetic assimilation to support so-calledLamarckian inheritance. They denied that the inheritance of acquired characteristics had taken place, and asserted that Waddington had simply observed the natural selection of genetic variants that already existed in the study population.[14] Waddington himself interpreted his results in aNeo-Darwinian way, particularly emphasizing that they "could bring little comfort to those who wish to believe that environmental influences tend to produce heritable changes in the direction of adaptation."[1][15][16]The evolutionary developmental biologist Adam S. Wilkins wrote that "[Waddington] in his lifetime... was widely perceived primarily as a critic of Neo-Darwinian evolutionary theory. His criticisms ... were focused on what he saw as unrealistic, 'atomistic' models of both gene selection and trait evolution." In particular, according to Wilkins, Waddington felt that the Neo-Darwinians badly neglected the phenomenon of extensive gene interactions and that the 'randomness' of mutational effects, posited in the theory, was false.[17] Even though Waddington became critical of theneo-Darwinian synthetic theory of evolution, he still described himself as a Darwinian, and called for anextended evolutionary synthesis based on his research.[18] Waddington did not deny the threshold-based conventional genetic interpretation of his experiments, but regarded it "as a told to the children version of what I wished to say" and considered the debate to be about "mode of expression, rather than of substance".[19]Both genetic assimilation and the relatedBaldwin effect are theories ofphenotypic plasticity, where aspects of an organism's physiology and behaviour are affected by the environment. The evolutionary ecologist Erika Crispo states that they differ in that genetic assimilation decreases the level of plasticity (returning to Waddington's original definition of canalization; whereas the Baldwin effect may increase it) but does not change the mean phenotypic value (where the Baldwin effect changes it).[20] Crispo defines genetic assimilation as a kind of genetic accommodation, "evolution in response to both genetically based and environmentally induced novel traits",[20] which in turn is in her view central to the Baldwin effect.[20]
Mathematical modeling suggests that under certain circumstances, natural selection favours the evolution of canalization that is designed to fail under extreme conditions.[21][22] If the result of such a failure is favoured by natural selection, genetic assimilation occurs. In the 1960s, Waddington and his colleague the animal geneticist J. M. Rendel argued for the importance of genetic assimilation in natural adaptation, as a means of providing new and potentially beneficial variation to populations under stress, enabling them to evolve rapidly.[23][24] Their contemporaryGeorge C. Williams argued that genetic assimilation proceeds at the cost of a loss of previously adaptivedevelopmental plasticity, and therefore should be seen as resulting in a net loss rather than gain of complexity, making it in his view uninteresting from the perspective of the constructive process of adaptation.[25] However, the preceding phenotypic plasticity need not be adaptive, but simply represent a breakdown of canalization.[21]
A 2023 transcriptomic analysis revealed that genetic assimilation in environmental adaptations is rare.[26]
Several instances of genetic assimilation have been documented contributing to natural selection in the wild. For example, populations of the island tiger snakes (Notechis scutatus) have become isolated on islands and have larger heads to cope with large prey animals. Young populations have larger heads by phenotypic plasticity, whereas large heads have become genetically assimilated in older populations.[27]
In another example, patterns of left-right asymmetry or "handedness", when present, can be determined either genetically or plastically. During evolution, genetically determined directional asymmetry, as in the left-oriented human heart, can arise either from a nonheritable (phenotypic) developmental process, or directly bymutation from a symmetric ancestor. An excess of transitions from plastically determined to genetically determined handedness points to the role of genetic assimilation in evolution.[28]
A third example has been seen inyeast. Evolutionary events in whichstop codons are lost preserve thereading frame much more often than would be expected frommutation bias. This finding is consistent with the role of theyeast prion [PSI+] in epigenetically facilitating stop codon readthrough, followed by genetic assimilation via the permanent loss of the stop codon.[3]
