canalization - senecio7の日記

Hallgrimsson B, Green RM, Katz DC, Fish JL, Bernier FP, Roseman CC, Young NM, Cheverud JM & Marcucio RS 2019 The developmental-genetics of canalization. Sem Cell Dev Biol 88:67-79.

canalization is a potentially significant cause of missing heritability

canalization, or the tendency to buffer variation, is about the modulation of phenotypic variance due to factors other than the genetic or environmental variance, per se
phenotypic robustness is a more general concept
canalization refers to the minimization of variation among individuals
developmental stability is the tendency to minimize variation among replicated structures within individuals
developmental stability is most often measured via random, normally distributed departures from symmetry where symmetrical development is expected, or fluctuating asymmetry
canalization and developmental stability are partially overlapping phenomena
it is not known, however, to what extent measures of canalization and developmental stability capture the same biological phenomena

canalization was motivated by developmental biology
phenotypic plasticity has a more naturalistic or population biology origin
coined by Woltereck [37], the concept of a reaction norm was fleshed out by Schmalhausen [38] whose primary interest was in the central role of stabilizing selection in evolution
independently of Waddington, Schmalhausen proposed a concept very similar to canalization which, in the English translation, he termed autonomization
for him, reaction norms, shaped by stabilizing selection, are adaptive
autonomization is not just any minimization of any variation
it is specifically the minimization of non-adaptive variation around the reaction norm
this contrasts significantly with current thinking on plasticity
plasticity is not necessarily adaptive

canalization and phenotypic plasticity are merely abstractions from patterns in data
they are not processes or mechanisms

the problem with viewing canalization as simply the inverse of plasticity is that plasticity is a much more general phenomenon
Wagner et al.'s [8] definition of canalization avoids this confusion
they define canalization as the suppression of phenotypic variation of either genetic or environmental origin
this makes canalization a dispositional concept, referring to a tendency or potential
canalization is the tendency to suppress variation
canalization is not a component of an observed phenotypic variance
it is a component of variability, or the tendency to vary
defined in this way, canalization is distinct from the more general concept of phenotypic plasticity
this definition also allows for the possibility of changes in among-individual variance along the norm of reaction
such changes in among-individual variance can result from a nonlinear norm of reaction curve
the shape of such norm of reaction curves can vary among genoytpes
they might also result from other factors such as destabilizing effects of environmental stress or genetic perturbations

these early studies showed that the tendency for increased among-individual variance in mutants responded to selection, suggesting a heritable basis for canalization

all genetic canalization effects are attributable to epistasis in a quantitative genetic sense
yet large, population-level quantitative genetic effects are no assurance that underlying biological interactions between genes and/or gene products are understood or can be identified in individuals
to say epistasis explains genetic canalization in a mechanistic sense is therefore to commit Roff's sin of confounding a quantitative model with a mechanistic explanation
at the heart of this issue is the fact that quantitative genetics and developmental biology are concerned with different kinds of questions and have different definitions of ostensibly the same phenomena
quantitative genetics is concerned with partitioning phenotypic outcomes into cumulative, statistically-defined phenomena
developmental biology is concerned with physical mechanisms such as specific molecular, cellular or tissue-level interactions
the genetics of a population of clones is singularly uninteresting
its developmental biology may be fascinating
quantitative genetics defines most phenomena at the population level and is fundamentally concerned with variation
the mechanisms of interest to developmental biology occur in individuals and, at least under the current paradigm, variation is more often a nuisance than a direct object of study
in genetics, epistasis is a statistical effect
in developmental biology it is generally viewed as a mechanistic interaction between gene products
the two versions of epistasis are linked conceptually but are not identical
canalization is a property of individuals that is almost always measurable only at a population level
in genetic terms, a genetic factor increases canalization if, all else being equal, it reduces the phenotypic variance
for genetic canalization, the influence of a gene on the phenotypic effect of other genes is, by definition a case of epistasis
genetic variation in such effects could be described as differential epistasis
does this mean that epistasis fully explains genetic canalization?
not necessarily
gene interaction effects imply nonlinear effects on phenotype
this is a statistical model of variation and not a mechanistic description of actual physical interactions
nonlinearities in development arise in myriad ways
depending on one's perspective (genetic or developmental), epistasis can be seen as either a cause or a consequence of canalization

for genes with redundant functions, null mutations might, therefore, be expected to produce a viable but more variable phenotype
conversely, redundancy in gene function contributes to robustness to mutation in those genes

the mapping of gene expression to phenotype is highly nonlinear
loss of over 50% of the wildtype expression level is associated with minimal changes in phenotype
beyond this point, the phenotypic effects are large and increasingly severe
we extended variation in Fgf8 expression well beyond the range expected in natural populations
this begs the question of how such nonlinearities evolve
the local flattening of the gene-expression to phenotype around the wildtype could evolve by stabilizing selection acting on gene-interaction effects
the question of how stabilizing or directional selection influence variational properties such as canalization has been an area of significant debate

diversity, often originating in different disciplines, has also created a situation reminiscent of the parable of the blind men and the elephant
each tends to be concerned with a particular aspect of the problem, making it difficult to contextualize this progress in terms of a more general understanding of the mechanisms of canalization in development