Bias in the introduction of variation

[3][4][5][6][7] Whereas mutational explanations for evolutionary patterns are typically assumed to imply or require neutral evolution, the theory of arrival biases distinctively predicts the possibility of mutation-biased adaptation.

[11][13] This theory is notable as an example of contemporary structuralist thinking, contrasting with a classical functionalist view in which the course of evolution is determined by natural selection (see [14]).

[19] The second thread is a long history of attempts to establish the thesis that mutation and development exert a dispositional influence on evolution by presenting options for subsequent functional evaluation, i.e., acting in a manner that is logically prior to selection.

In the early 20th-century, authors such as Eimer or Cope held that development constrains or channels evolution so strongly that the effect of selection is of secondary importance.

Similar thinking featured in the emergence of evo-devo, e.g., Alberch (1980) suggests that "in evolution, selection may decide the winner of a given game but development non-randomly defines the players" (p. 665)[25] (see also [26]).

Thomson (1985), [27] reviewing multiple volumes addressing the new developmentalist thinking— a book by Raff and Kaufman (1983) [28] and conference volumes edited by Bonner (1982) [29] and Goodwin, et al (1983) [30] — wrote that "The whole thrust of the developmentalist approach to evolution is to explore the possibility that asymmetries in the introduction of variation at the focal level of individual phenotypes, arising from the inherent properties of developing systems, constitutes a powerful source of causation in evolutionary change" (p. 222).

[32] and Bruce Wallace ("problems concerned with the orderly development of the individual are unrelated to those of the evolution of organisms through time"), [33] as being inconsistent with accepted concepts of causation.

Under this proposal, the key to understanding the structuralist thesis of the developmental biologists was a previously missing population-genetic theory for the consequences of biases in introduction.

The theory, which applies to both mutational and developmental biases, addresses how such preferences can be effective in shaping the course of evolution even while strong selection is at work.

However, the implications of the theory have not been tested critically in regard to morphological and behavioral traits in animals and plants that are the traditional targets of evolutionary theorizing (see Ch.

As noted above, in the simplest case of the "Climbing Mount Probable" effect, one may consider a climber facing just two fixed choices: up and to the left, or up and to the right.

This result validates the intuition of Shull [53] that "It strains one's faith in the laws of chance to imagine that identical changes should crop out again and again if the possibilities are endless and the probabilities equal" (p. 448).

For instance, in a simulation of adaptive walks of protein-coding genes in the context of an abstract NK landscape,[8] the effect of a GC-AT mutation bias is to alter the protein sequence composition in a manner qualitatively consistent with the analogy of Climbing Mount Probable (above).

[8] For instance, adaptive walks under a mutation bias toward GC result in proteins that have more of the amino acids with GC-rich codons (Gly, Ala, Arg, Pro), and likewise, adaptive walks under AT bias result in proteins with more of the amino acids with AT-rich codons (Phe, Tyr, Met, Ile, Asn, Lys).

Likewise, the theory implies that evolution can have directions that are not adaptive, or tendencies that are not optimal, an implication one commentator on Arthur's book[46] found "disturbing".

In contrast to what is implied by the language of "constraints" or "limits" employed in historic appeals to internal sources of direction in evolution, the theory of arrival biases is not deterministic and does not require an absolute distinction between possible and impossible forms.

In classical neo-Darwinian thinking, selection governs and shapes evolution, whereas variation plays a passive role of supplying materials.

transversions favored by mutT (left block of bars) are highly enriched among resistant isolates from mutT parents (blue in the accompanying figure), and likewise, the resistant strains from mutH parents (red) tend to have the nucleotide transition mutations favored by mutH (center block of bars).

A different use of available evidence is to focus on the idea of graduated effects, which distinguishes the theory of arrival biases from the intuitive notion of "constraints" or "limits" on possible forms.

The frequency with which a resistant variant appears in the set of 284 replicate cultures correlates strongly and roughly linearly with the mutation rate (figure at right).

For instance, Darwin's comment that the laws of variation "bear no relation" to the structures built by selection would suggest that there are no conditions under which the internal details on the left account for the patterns on the right.

This late emergence has been attributed to a "blind spot" due to multiple factors,[15] including a tradition of verbal arguments that minimize the role of mutation, a tendency to associate causation with processes that shift frequencies of variants rather than processes that create variants, and a formal argument from population genetics that doesn't extend to evolution from new mutations.

The Haldane-Fisher "opposing pressures" argument was used repeatedly by leading thinkers to reject structuralist or internalist thinking (examples in [2] or Ch.

Seventy years later Gould (2002), citing Fisher (1930), wrote that “Since orthogenesis can only operate when mutation pressure becomes high enough to act as an agent of evolutionary change, empirical data on low mutation rates sound the death-knell of internalism.” (p. 510)[93] In this way, arguments from population genetics were used to reject, rather than support, speculative claims about the role of variational tendencies.

However, toward the end of the 20th century, theoreticians began to note that long-term dynamics depend on events of mutational introduction not covered in classical theory.

However, the number of mutations leading from the starting network to P2 is 4 times higher illustrating the idea that, for a given developmental-genetic system, some phenotypes are more mutationally accessible.

In a different framing per,[15][2] the efficacy of arrival biases undermines the historic commitment of theoreticians to viewing evolution as a process of shifting gene frequencies in an abundant gene pool, dominated by mass-action forces, and is part of a larger movement (beginning during the molecular revolution) away from the neo-Darwinism of the Modern Synthesis and towards a version of mutationism grounded in population genetics.

When mutation bias is included in models of a single quantitative trait under stabilizing selection, the result is a small displacement from the optimal value.

[37] Whereas the effectiveness of absolute biases does not require a special causal theory (because a developmentally impossible form is an evolutionarily impossible form), the idea of graduated biases prompts questions of causation, due to the conflict with the classic Haldane-Fisher "opposing pressures" argument, which holds that mere variational tendencies are ineffectual because mutation rates are small.

[6] That is, the theory does not assume that biases are beneficial with respect to fitness, and it does not propose that mutation somehow contributes to adaptedness separately from the effect of selection (contra [113] ).

Biased outcome of 1-step adaptation under the Yampolsky-Stoltzfus model . Denoting the two outcomes as "left" (higher ) and "right" (higher ), the left/right ratio of outcomes is shown as a function of mutation bias . For smaller , outcome bias is close to the origin-fixation approximation . Values of are 0.02 (right) and 0.01 (left), thus . The higher (left) is , whereas the lower (right) varies according to . Vertical bars: standard error.
From mutation bias to developmental bias The Yampolsky-Stoltzfus model (above), used to demonstrate the effect of biases in introduction, is agnostic about the source of biases. For instance, the genotype-phenotype map for codons (the genetic code ) dictates that, starting with Met and assuming uniform mutation (no mutation bias), there is a 3-fold phenotype bias in the introduction of the Ile phenotype relative to Val.
The coefficient of mutational influence shows effects of mutation supply and breadth of beneficial options (after Figure 4 of [ 7 ] ). (A) The total effect of mutation on the spectrum of computer-simulated adaptive changes (from repeated 1-step adaptation) is given by (expected range, 0 to 1) for different levels of mutation supply. The value of is also influenced by the diversity of possible beneficial mutations, which can be measured by entropy. (B) The correlation (Pearson’s ) of observed and predicted results as a function of the entropy of the simulated spectra of adaptive substitutions.
The mutation spectrum shapes the spectrum of changes underlying cefotaxime adaptation . The counts of resistant variants in ftsI from Couce, et al (2015) are grouped by mutation and parent strain (rows). MutT -derived strains (top row, blue) tend to have the kinds of mutations favored by mutT (left block of columns, AT to CG transversions). MutH -derived straints (middle row, red) tend to have nucleotide transitions (middle block of columns) favored by mutH .
Nucldeotide transitions dominate experimental adaptation in 4 microvirid phages. Transversions are in black (data from Table 1 of [ 10 ] ).
A roughly proportional effect of mutation rate on the chance of evolving. The frequency evolved (in replicate cultures) as a function of mutation rate for 11 resistance variants from MacLean, et al (2010)
Frequency of nucleotide changes in three data sets of adaptive changes correlate closely with de novo mutation rates for the 6 types of nucleotide-to-nucleotide changes (data from [ 7 ] ).
Applying theories of the consequences of variational tendencies to explaining evolutionary patterns . The green arrow represents any theory that might connect variational tendencies with evolutionary tendencies, allowing us to account for patterns on the right by appealing to details on the left
The shifting gene frequencies theory This US science policy document from 2001 [ 94 ] defines evolution as shifting gene frequencies, and identifies the two main causes of evolution as selection and drift. Origin-fixation models represent a different conception of evolution in which introduction and fixation (by selection or drift) are the two main causal processes. [ 19 ]
A bias induced by a GP map via the phenocopy effect
Differential local accessibility and long-term findability of phenotype networks in genotype-space Connected networks for 3 different phenotypes, showing that, from P0, P2 is more accessible than P1. In the long-term, what matters is that P0 has twice as many genotypes as P1 and P2 (after fig 4 of Fontana 2002)
Findable RNA folds (Fig 2 of [ 82 ] ). The frequency of folds in sequence space is shown as a function of frequency rank, considering several different sequence lengths and levels of aggregation of folds. The folds found in nature are highlighted with yellow circles.
Evolution by mutation pressure . A population of size N = 20 (rows) is transformed over 100 generations (columns) by red-to-blue mutation (u = 0.025). For simplicity, each individual has exactly 1 offspring (thus fitness is the same for red and blue). Simulations from the evolvulator , an online educational tool.