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STRUCTURAL AND FUNCTIONAL DIVERSITY OF THE EUKARYOTIC GENOME

Brno, Czech Republic, October 14-16, 2010

Metaptation:

Metaphors for Genome Evolution

David G. King

Southern Illinois University CarbondaleU.S.A.

Metaphor an implicit comparison; a tool for thinking.

Metaptation a neologism; the subject of this talk.

a fable of a grasshopper . . .

Image by Milo WinterAesop’s Fables, 1919


Genes need “tuning knobs” !

Simple Sequence Repeats behave like tuning knobs.

Incremental adjustability

Repeat number mutations typically exert small effects on phenotype.

Reversibility

Any shift in repeat number can be readily reversed.

Modularity

Each example has its own characteristics.

A concrete function:

a “setting” (parameter value).

An abstract function:

a “protocol” (adjustability).

A tuning knob has dual functionality.

Protocol of adjustability

Motifs

Microsatellites

mononucleotides e.g., polyA • polyT

dinucleotides e.g., ACn • GTn

trinucleotides e.g., CAGn • CTGn

tetra-, penta-, hexanucleotides

Minisatellites

longer motifs, up to tens of nucleotides

Functional domains

practically anywhere!

exons

introns

UTRs

upstream, downstream

et cetera

Protocol of adjustabilityembodied by simple sequence repeats

A protocol is an implicit rule or architecture

that defines permissible avenues for

behavior.

A genetic protocol imposes "grammatical"

constraints on genetic variation.

An advantageous genetic protocol enhances the probability of beneficial mutation.

Some advantageous protocols.

(adaptively plausible constraints on genetic variation)

Incremental adjustability (simple sequence repeats).

Cut and paste (transposable elements).

Mix and match (meiotic recombination).

Programmed gene rearrangement (e.g., trypanosomes).

On / off switching (bacterial contingency genes).

Many more . . . ?

Questions of protocol

Do evolutionary protocols just happen (by accident)?

orHave protocols evolved because they are evolutionarily advantageous?

If protocols have evolved, how could this be possible?

A conceptual difficulty . . .

An advantageous protocol can raise the mutation rate for variation arising within the constraints of the protocol.

But the idea that mutation rates might increase for evolutionary advantage is contrary to conventional evolutionary theory.

Image from Wikipedia Commons

Natural selection of mutation rates has only one possible direction, that of reducing the frequency of mutation to zero.

Evolution has probably reduced mutation rates to far below species optima, as the result of unrelenting selection for zero mutation rate in every population.

George C. Williams

Adaptation and Natural Selection, 1966

If genetic variation arises within the constraints of a protocol, selection for those variants must indirectly select the protocol.


A semantic difficulty . . .

Protocols cannot be adaptations, because an “adaptation” by definition is shaped by natural selection.

And protocols are invisible to natural selection.


Natural selection shapes adaptations by acting on phenotypes.

Natural selection sees the grasshopper.

Natural selection cannot see the the implicit protocols in the grasshopper’s genome.


A simple semantic solution:

If an advantageous protocol cannot properly be called an adaptation,

Let us call it a “metaptation.”


An adaptation is an advantageous phenotypic trait.

The process of adaptation is how such phenotypic traits evolve, by natural selection for fitness.

* * *A metaptation is an advantageousgenetic protocol.

The process of metaptation is how protocols evolve by indirect selection.


Metaptation [meta, change, transcend + aptation, fitness]

1. an evolutionary process by which natural selection indirectly shapes genomic “protocols” that facilitate evolutionary adaptation.

2. any of the resulting “protocols for effective evolution”.

Evolutionary Theory (1985) 7:22



A metaptation is a genomic pattern or

architecture – a protocol – which constrains

the effect of mutation and enhances

the probability of adaptive benefit.

What the devil determines each particular variation? What makes a tuft of feathers come on a cocks head, or moss on a moss rose? Charles Darwin letter to T.H. Huxley, 25 Nov 1859

A grand and almost untrodden field of inquiry will be opened, on the causes and laws of variation . . .

Charles Darwin On the Origin of Species, 1859

Available at www.zoology.siu.edu/king/Brno.htm

reference list

text of talk

PowerPoint slides


Simple sequence repeats / Indirect selection for "tuning knobs" King DG (1985) Metaptation: A descriptive category for evolutionarily versatile patterns of genetic and ontogenetic organization. Evol Theor 7: 222.

Trifonov EN (1989) The multiple codes of nucleotide sequences. Bull Math Biol 51: 417–432.

Gerber H-P et al. (1994) Transcriptional activation modulated by homopolymeric glutamine and proline stretches. Science 263: 808-811.

Rosenberg SM et al. (1994) Adaptive mutation by deletions in small mononucleotide repeats. Science 265: 405-407.

Kashi Y, King DG, and Soller M (1997) Simple sequence repeats as a source of quantitative genetic variation. Trends in Genetics 13: 74-78.

King DG, Soller M, and Kashi Y (1997) Evolutionary tuning knobs. Endeavour 21: 36-40.

King, DG, and Soller, M (1999) Variation and fidelity: The evolution of simple sequence repeats as functional elements in adjustable genes. In: S.P. Wasser, ed., Evolutionary Theory and Processes: Modern Perspectives, Kluwer Academic Publishers, Dordrecht, pp. 65-82.

Fondon III JW and Garner, HR (2004) Molecular origins of rapid and continuous morphological evolution. PNAS 101(52): 18058-18063.

Li Y-C et al. (2004) Microsatellites within genes: Structure, function, and evolution. Mol Biol Evol 21: 991-1007.

Verstrepen KJ et al. (2005) Intragenic tandem repeats generate functional variability. Nature Genet 37: 986–990.

Kashi Y and King DG (2006a) Simple sequence repeats as advantageous mutators in evolution. Trends Genet 22: 253-259.

Kashi Y and King DG (2006b) Has simple sequence repeat mutability been selected to facilitate evolution? Isr J Ecol Evol 52: 331-342.

King DG, Trifonov EN, and Kashi, Y (2006) Tuning knobs in the genome: Evolution of simple sequence repeats by indirect selection. In: LH Caporale, ed., The Implicit Genome, Oxford University Press, pp. 77-90.

King DG and Kashi Y (2007a) Mutability and Evolvability: Indirect selection for mutability. Heredity 99: 123-124.

King DG and Kashi Y (2007b) Mutation rate variation in eukaryotes: evolutionary implications of site-specific mechanisms. Nature Rev Genet 8 (doi:10.1038/nrg2158-c1).

Vinces MD, Legendre M, Caldara M et al. (2009) Unstable tandem repeats in promoters confer transcriptional evolvability. Science 324: 1213-1216.

Evolutionary protocols (other than “tuning knobs”)

Arber W (2005) Gene products with evolutionary functions. Proteomics 5: 2280-2284.

Barry JD (2006) Implicit information in eukaryotic pathogens as the basis of antigenic variation. In: Caporale LH, ed. The Implicit Genome. Oxford: Oxford University Press, pp. 91-106.

Bayliss CD, Moxon ER (2006) Repeats and variation in pathogen selection. In: Caporale LH, ed., The Implicit Genome. Oxford: Oxford University Press, pp. 54-76.

Caporale LH (1999) Chance favors the prepared genome. In: Caporale, L. H., ed. Molecular Strategies in Biological Evolution, Ann. N. Y. Acad. Sci . 870: 1-21.

Caporale LH (2000) Mutation is modulated: Implications for Evolution. Bioessays 22: 388-395.

Caporale LH (2003) Foresight in genome evolution. Amer. Sci.. 91: 234-241.

Caporale LH. (2003) Natural selection and the emergence of a mutation phenotype: An update of the evolutionary synthesis considering mechanisms that affect genomic variation. Ann. Rev. Microbiol. 57: 465-485.

Caporale LH (2006) The Implicit Genome. Oxford: Oxford University Press, pp. 91-106.

Csete M and Doyle J (2002) Reverse engineering of biological complexity. Science 295: 1664-1669.

Doyle J, Csete M and Caporale LH (2006) An engineering perspective: The implicit protocols. In: Caporale LH, ed., The Implicit Genome. Oxford: Oxford University Press, pp. 294-298.

Doyle & Csete (2007) Rules of engagement. Nature 446: 860.

Kirschner M and Gerhart J (1998) Evolvability. Proc. Natl. Acad. Sci. USA 95: 8420-8427.

Mihola O et al. (2009) A Mouse Speciation Gene Encodes a Meiotic Histone H3 Methyltransferase. Science 328:373-375.

Oliver KR, Green WK (2009) Transposable elements: powerful facilitators of evolution. BioEssays 31: 703–714.

Shapiro JA (1983) Variation as a genetic engineering process. Pp. 253-270, in D.S. Bendall, ed. Evolution from Molecules to Men, Cambridge University Press, Cambridge.

Shapiro JA (1997) Genome organization, natural genetic engineering and adaptive mutation. Trends Genet 13:98-104.

Thaler D (1994) The evolution of genetic intelligence. Science 264: 224-225.

Contrary literature

Bridges CB (1919) Specific modifiers of eosin eye color in Drosophila melanogaster. J Exp Zool 28(3): 37-384.

Sturtevant AH (1937) Essays on evolution. I. On the effects of selection on mutation rate. Q Rev Biol 12: 464-467.

Williams GC (1966) Adaptation and Natural Selection. Princeton: Princeton University Press, 1966.

Sniegowski PD, Gerrish PJ, Johnson T et al. (2000) The evolution of mutation rates: separating causes from consequences. Bioessays 22: 1057-1066.

Sniegowski PD, Murphy HA (2006) Evolvability. Current Biology 16: R831-R834.

In everyday usage, protocols are rules designed to manage relationships and processes smoothly and effectively.

If modules are ingredients, parts, components, subsystems, and players, then protocols describe the corresponding recipes, architectures, rules, interfaces, etiquettes, and codes of conduct.

Protocols here are rules that prescribe allowed interfaces between modules, permitting system functions that could not be achieved by isolated modules. Protocols also facilitate the addition of new protocols and organization into collections of mutually supportive protocol suites.

Thinking in terms of protocols, in addition to genes, organisms, and populations, as foci of natural selection, may be a useful abstraction for understanding the evolution of complexity.

Good protocols allow new functions to be built from existing components and allow new components to be added or to evolve from existing ones, powerfully enhancing both engineering and evolutionary “tinkering.”Successful protocols become highly conserved because they both facilitate evolution and are difficult to change.

Marie Csete and John Doyle 2002 (Science 295:1664)

Far from being clumsy stumblers into random point

mutations, genomes have evolved mechanisms that

facilitate their own evolution.

These mechanisms diversify a genome and increase

the probability that its descendants will survive.

Lynn Helena Caporale 1998 (Annals N.Y. Acad. Sci. 870)

Any organism as it now exists must be regarded as a very complex physicochemical machine with delicate adjustments of part to part. Any haphazard change made in this mechanism would almost certainly result in a decrease of efficiency.

Only an extremely small proportion of mutations may be expected to improve a part or the interrelation of parts in such a way that the fitness of the whole organism for its available environments is increased.

Bridges 1919 (J Exp Zool 28 [3]: 37)

It seems at first glance that there should be a counter-selection, due to the occurrence of favorable mutations. It is true that favorable mutations furnish the only basis for improvement of the race, and must be credited with being the only raw material for evolution. It would evidently be fatal for a species, in the long run, if its mutation rate fell to zero, for adjustment to changing conditions would then not long remain possible. While this effect may occur, it is difficult to imagine its operation. . .

[F]or every favorable mutation, the preservation of which will tend to increase the number of genes in the population that raises the mutation rate, there are hundreds of unfavorable mutations that will tend to lower it. Further, the unfavorable mutations are mostly highly unfavorable, and will be more effective in influencing the rate than will the relatively slight improvements that can be attributed to the rare favorable mutations.

[W]hy does the mutation rate not become reduced to zero? No answer seems possible at present, other than the surmise that the nature of genes does not permit such a reduction. In short, mutations are accidents, and accidents will happen.

Sturtevant 1937 (Q Rev Biol 12: 464)

One frequently hears that natural selection will not produce too low a

mutation rate because that would reduce the evolutionary plasticity of the

species.

[N]atural selection of mutation rates has only one possible direction, that

of reducing the frequency of mutation to zero. That mutations should

continue to occur requires no special explanation. It is merely a reflection

of the unquestionable principle that natural selection can often produce

mechanisms of extreme precision, but never of perfection. . .

Evolution has probably reduced mutation rates to far below species

optima, as the result of unrelenting selection for zero mutation rate in

every population. George Williams Adaptation and Natural Selection, 1966

[I]t can be appealing to suppose that the genomic mutation rate is adjusted to a

level that best promotes adaptation. Most mutations with phenotypic effects are

harmful, however, and thus there is relentless selection within populations for

lower genomic mutation rates. Selection on beneficial mutations can counter

this effect by favoring alleles that raise the mutation rate, but the effect of

beneficial mutations on the genomic mutation rate is extremely sensitive to

recombination and is unlikely to be important in sexual populations.

The physiological cost of reducing mutation below the low level observed in

most populations may be the most important factor in setting the genomic

mutation rate in sexual and asexual systems, regardless of the benefits of

mutation in producing new adaptive variation. Maintenance of

mutation rates higher than the minimum set by this 'cost of fidelity'

is likely only under special circumstances.

Sniegowski et al. 2000 (BioEssays 22:1057)

Some authors believe it to be as much the function of the reproductive system to produce individual differences, or very slight deviations of structure, as to make the child like its parents. Charles Darwin On the Origin of Species, 1859

Drosophila melanogaster

cervical connective

Dolichopodidae

Empididae

Rhagionidae

Micropezidae

Glossinidae

Asilidae

Anthomyiidae

Psychodidae

Muscidae

Can we find protocols for mutation, which can facilitate the

evolutionary adjustment of adaptive traits, such as details of

individual nerve cells?

Ephydridae

Charles Darwin again:

A grand and almost untrodden field of inquiry will be opened,

on the causes and laws of variation . . .

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