CAMP EVOLUTION VI - EVOLUTION ON FITNESS LANDSCAPES

 

Fitness landscape is a unifying concept of evolutionary biology. We will use it to consider a wide range of seemingly unrelated evolutionary phenomena at all levels of organization.

 

 

Introduction

 

1) Complex fitness landscapes

Fitness landscapes, maps from the space of genotypes or phenotypes into fitness, is the key conceptual tool for studying evolution of life. Usually, fitness landscapes are complex, due to epistasis, deviation of fitness of a genotype from the product of contributions of the constituent alleles. On top of generic fitness landscapes, it often makes sense to consider special cases of epistasis: one-dimensional (fitness is an arbitrary function of a simple, scalar characteristic of a genotype), single-peak (adaptive evolution from any initial conditions will lead to the same genotype), and monotonic (one of two alleles confers a higher fitness on any genetic background). There is a specific fitness landscape for every environment, and families of fitness landscapes are characterized by bifurcations.

 

Whitlock MC (1995) Multiple fitness peaks and epistasis. Ann. Rev. Ecol. Syst. 26, 601-629

 

de Visser JAGM, Krug J (2014) Empirical fitness landscapes and the predictability of evolution. Nature Reviews Genetics 15, 480-490

 

 

 

2. Fitness landscapes of molecules

 

2a) Compensated pathogenic deviations and ongoing expansion of protein universe

Homologous sites of homologous proteins (and of functional RNAs) may be under different modes of selection. In particular, an amino acid which is pathogenic, at a particular site of a particular protein, for humans, may be occupy the homologous site of the wild-type homologous protein in another organism. This phenomenon, known as compensated pathogenic deviation, can be used to study fitness landscapes of proteins. Analogously, ongoing divergence of homologous proteins even after they accumulated several neutral allele replacements per site would be impossible without epistasis, and can reveal some of its quantitative properties.

 

Povolotskaya IS, Kondrashov FA (2010) Sequence space and the ongoing expansion of the protein universe. Nature 465, 922-926

 

Jordan DM et al. (2015) Identification of cis-suppression of human disease mutations by comparative genomics. Nature 524, 225-229

 

Storz F (2018) Compensatory mutations and epistasis for protein function. Current Opinion in Structural Biology 50, 18-25

 

 

2b) Empirical fitness landscapes, experimental evolution, and protein design

Existing proteins and other biological objects cover only a tiny proportion of the space of genotypes. Thus, complete fitness landscapes are hidden in the darkness of non-existence. The only way to get them out of there is to create more proteins. This can be done by taking the existing protein as a point of departure and analyzing some volume of the space of genotypes around it. Such studies revealed pervasive narrowing epistasis. Alternatively, fitness landscape can be explored by artificial evolution of a protein directed toward some new function. Information about fitness landscapes will facilitate designing of proteins with novel functions.

 

Philip A. Romero PA, Arnold FH (2009) Exploring protein fitness landscapes by directed evolution. Nature Reviews Molecular Cell Biology 10, 866-876

 

Sarkisyan KS et al. (2016) Local fitness landscape of the green fluorescent protein. Nature 533, 397-401

 

Wrenbeck EE (2017) Deep sequencing methods for protein engineering and design. Current Opinion in Structural Biology 45, 36-44

 

 

 

3. Fitness landscapes of cells

 

3a) Evolution of functional units within a cell

Functioning of a living cell is governed by complex networks of interactions between genes, proteins, and small molecules. Evolution of a gene or a protein is restricted by interactions in which it participates, and these interactions can be understood only in the context of the fitness landscape of the cell. This paradigm produces new insights into evolution of individual genes and proteins. When this context evolves, even the key property of a gene, its essentiality, can also evolve. Landscapes of multiple regulatory genes which perform similar functions can be also very similar to each other. Promiscuous interactions facilitate the origin of new regulatory functions.

 

Haldane A et al. (2014) Biophysical fitness landscapes for transcription factor binding sites. PLoS Comput. Biol. 10(7): e1003683

 

Friedlander T et al. (2016) Evolution of new regulatory functions on biophysically realistic fitness landscapes. Nature Comm. 8: 216

 

Rancati G et al. (2017) Emerging and evolving concepts in gene essentiality. Nature Reviews Genetics doi:10.1038/nrg.2017.74

 

 

3b) Global properties of fitness landscapes of cells

Fitness landscape of even the simplest cell must be incredibly complex. It has longed being suspected that they are very "rugged" (possess multiple peaks), and recent data on adaptive evolution confirm this. Networks of interactions within cells are known to be modular, but the reasons for this remain obscure. One possibility is that modularity emerges as a result of selection for higher computational efficiency, if the fitness landscape often undergoes bifurcations. The global fitness landscape of a cell can be very fragile and undergo many radical changes after a single amino acid substitution within an important regulatory protein.

 

Peter L. Freddolino PL et al. (2012) Fitness landscape transformation through a single amino acid change in the rho terminator. PLoS Genetics 8(5): e1002744

 

Van Clevea J, Weissman DB (2015) Measuring ruggedness in fitness landscapes. PNAS 112, 7345-7346

 

Tosh CR (2016) Can computational efficiency alone drive the evolution of modularity in neural networks? Scientific Reports 6:31982

 

 

 

4. Fitness landscapes of organisms

 

4a) Mutation load and the evolution of sex

Genomic deleterious mutation rate in humans is ~10, and, as long as fitness landscape is non-epistatic, this must lead to an intolerable genetic load. Some data indicate that narrowing epistasis is present, however, more information is needed. Whatever forces are responsible for generation of linkage disequilibria and for overrepresented genotypes to have reduced fitnesses - the two conditions for the advantage of sex and recombination - they cannot cause a substantial advantage of a recombination-increasing modifier unless selection differential is comparable to the standard deviation of fitness potential. Such strong, directional selection is not out of the question; however, it is not clear why it should be pervasive among eukaryotes.

 

Barton NH (2009) Why sex and recombination? Cold Spring Harbor Symp. Quant. Biol. 54, 1-9

 

Kondrashov AS (2017) Crumbling Genome, Wiley.

 

Sohail M et al. (2017) Negative selection in humans and fruit flies involves synergistic epistasis. Science 356, 539-542

 

 

4b) Punctuated equilibrium revisited

Over 30 years ago, a debate raged among evolutionary biologists on whether evolution is gradual or consists of short bursts alternating with periods of stasis. As usual in our field, the subject was eventually quietly abandoned, without any clear resolution. However, the only codimension 1 bifurcation of a fitness landscape, "fold catastrophe", leads to an abrupt disappearance of a fitness peak and, thus, appears to be capable of inducing a rapid adaptive walk. Recent phylogenetic data made it possible to study such walks in evolution of individual proteins. So far, the results are mixed, but the subject is worth revisiting.

 

Dodson MM, Hallam A (1977) Allopatric speciation and the fold catastrophe. American Naturalist 111, 415-433

 

Richter H, Engelbrecht A, eds. (2014) Recent Advances in the Theory and Application of Fitness Landscapes. Springer, chapter 11

 

Pennell MW (2014). Is there room for punctuated equilibrium in macroevolution? Trends in Ecology and Evolution 29, 23-32

 

 

 

5. Fitness landscapes of populations

5a) Frequency-dependent selection, multilevel selection, evolution of cooperation

Fitness landscape of the population can depend on its state, which readily leads to extremely complex dynamics, especially when the population is structured. There is no general theory of such dynamics; instead, specific biological problems can be considered. Some data indicate that in the course of human history negative frequency-dependent selection favored rare facial features. Pairwise interactions between individuals can lead to evolution of indirect reciprocity, based on reputation. Group selection can favor strong emotional bound between individuals who together shared a negative experience.

Nowak MA, Sigmund K (2005) Evolution of indirect reciprocity. Nature 437, 1291-1298

 

Sheehan MJ, Nachman MW (2014). Morphological and population genomic evidence that human faces have evolved to signal individual identity. Nature Communications 5:4800

 

Harvey Whitehouse H et al. (2017) The evolution of extreme cooperation via shared dysphoric experiences. Scientific Reports 7: 44292

 

 

5b) Red Queen dynamics, Darwinian extinction, community assembly

Fitness landscape of the population can also depend on populations of other species in the same community. Again, the resulting dynamics can be very complex, and no general theory exists. In many cases ecological interactions between coevolving populations lead to endless changes of their fitness landscapes, known as Red Queen dynamics. A number of nonlinear effects can cause extinction of a population, as a result of its adaptive evolution. The process of community assembly depends critically on coevolution of interacting populations.

 

Webb C (2003) A complete classification of Darwinian extinction in ecological interactions. American Naturalist 161, 181-205

 

Nemergut DR et al. (2013) Patterns and processes of microbial community assembly. Microbiol. Mol. Biol. Rev. 77, 342-356

 

Richter H, Engelbrecht A, eds. (2014) Recent Advances in the Theory and Application of Fitness Landscapes. Springer, chapters 11 and 12