Theory Of Molecular Evolution Research Articles

Non-darwinian theories of biological evolution

The article presents material related to evolutionary theories such as Berg’s nomogenesis, Kimura’s theory of neutral evolution, and neo-Lamarckism, the content of which is opposed to Darwin’s doctrine of natural selection as a leading factor in biological evolution. Nomogenesis, a hypothesis according to which the evolution of organisms is based on internal laws. The general thesis of Berg’s worldview was that evolution occurs naturally, in accordance with a pre-existing – pre-established – law of development. The neutral theory of molecular evolution was put forward by Motoo Kimura. It argues that the vast majority of mutations at the molecular level are neutral in nature with respect to the action of natural selection. Thus, the theory of neutral evolution contradicted Darwinism, pointing to the fixation of neutral mutations in the population without the participation of natural selection. Neo-Lamarckism is a combination of three heterogeneous trends in evolutionary doctrine. Despite the fact that neo-Lamarckists have deviated from the basic postulates of Lamarck, most of their concepts contain two provisions that correspond to Lamarck's laws. The first is the recognition of adequate variability that occurs under the direct or indirect influence of the environment and creates well-acquired adaptive traits. The second is the inheritance of similar traits in individual life.

The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder.

The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an 'effective population size' is often estimated from the amount of putatively neutral genetic diversity and is assumed to also capture a species' effectiveness of selection. A potentially more direct measure of the effectiveness of selection is the degree to which selection maintains preferred codons. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here, we propose a new Codon Adaptation Index of Species (CAIS), based on Kullback-Leibler divergence, that corrects for both confounders. We demonstrate the use of CAIS correlations, as well as the Effective Number of Codons, to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics.

We integrate evolutionary predictions based on the neutral theory of molecular evolution with protein dynamics to generate mechanistic insight into the molecular adaptations of the SARS-COV-2 spike (S) protein. With this approach, we first identified candidate adaptive polymorphisms (CAPs) of the SARS-CoV-2 S protein and assessed the impact of these CAPs through dynamics analysis. Not only have we found that CAPs frequently overlap with well-known functional sites, but also, using several different dynamics-based metrics, we reveal the critical allosteric interplay between SARS-CoV-2 CAPs and the S protein binding sites with the human ACE2 (hACE2) protein. CAPs interact far differently with the hACE2 binding site residues in the open conformation of the S protein compared to the closed form. In particular, the CAP sites control the dynamics of binding residues in the open state, suggesting an allosteric control of hACE2 binding. We also explored the characteristic mutations of different SARS-CoV-2 strains to find dynamic hallmarks and potential effects of future mutations. Our analyses reveal that Delta strain-specific variants have non-additive (i.e., epistatic) interactions with CAP sites, whereas the less pathogenic Omicron strains have mostly additive mutations. Finally, our dynamics-based analysis suggests that the novel mutations observed in the Omicron strain epistatically interact with the CAP sites to help escape antibody binding.

Some mechanistic underpinnings of molecular adaptations of SARS-COV-2 spike protein by integrating candidate adaptive polymorphisms with protein dynamics

We integrate evolutionary predictions based on the neutral theory of molecular evolution with protein dynamics to generate mechanistic insight into the molecular adaptations of the SARS-COV-2 spike (S) protein. With this approach, we first identified candidate adaptive polymorphisms (CAPs) of the SARS-CoV-2 S protein and assessed the impact of these CAPs through dynamics analysis. Not only have we found that CAPs frequently overlap with well-known functional sites, but also, using several different dynamics-based metrics, we reveal the critical allosteric interplay between SARS-CoV-2 CAPs and the S protein binding sites with the human ACE2 (hACE2) protein. CAPs interact far differently with the hACE2 binding site residues in the open conformation of the S protein compared to the closed form. In particular, the CAP sites control the dynamics of binding residues in the open state, suggesting an allosteric control of hACE2 binding. We also explored the characteristic mutations of different SARS-CoV-2 strains to find dynamic hallmarks and potential effects of future mutations. Our analyses reveal that Delta strain-specific variants have non-additive (i.e., epistatic) interactions with CAP sites, whereas the less pathogenic Omicron strains have mostly additive mutations. Finally, our dynamics-based analysis suggests that the novel mutations observed in the Omicron strain epistatically interact with the CAP sites to help escape antibody binding.

Allele surfing causes maladaptation in a Pacific salmon of conservation concern.

How various factors, including demography, recombination or genome duplication, may impact the efficacy of natural selection and the burden of deleterious mutations, is a central question in evolutionary biology and genetics. In this study, we show that key evolutionary processes, including variations in i) effective population size (Ne) ii) recombination rates and iii) chromosome inheritance, have influenced the genetic load and efficacy of selection in Coho salmon (Oncorhynchus kisutch), a widely distributed salmonid species on the west coast of North America. Using whole genome resequencing data from 14 populations at different migratory distances from their southern glacial refugium, we found evidence supporting gene surfing, wherein reduced Ne at the postglacial recolonization front, leads to a decrease in the efficacy of selection and a surf of deleterious alleles in the northernmost populations. Furthermore, our results indicate that recombination rates play a prime role in shaping the load along the genome. Additionally, we identified variation in polyploidy as a contributing factor to within-genome variation of the load. Overall, our results align remarkably well with expectations under the nearly neutral theory of molecular evolution. We discuss the fundamental and applied implications of these findings for evolutionary and conservation genomics.

Neutral theory and beyond: A systematic review of molecular evolution education.

Molecular evolution-including the neutral theory of molecular evolution-is a major sub-discipline of evolution and is widely taught in undergraduate evolution courses. However, despite its ubiquity, there have not been any previous attempts to compile and review the molecular evolution education literature. Here, we draw upon the framework proposed in a past literature review examining the broader evolution education landscape to conduct a literature review of papers related to molecular evolution education, classifying the contributions of such papers to evolution pedagogy as well as evolution education research. We find that there remains very limited coverage of molecular evolution in the education literature, with existing papers focusing primarily on providing new instructional modules and strategies for teaching molecular evolution. Our work suggests several areas of critical need as well as opportunities to advance evolution education and evolution education research, including compiling instructional goals for the sub-discipline, developing validated assessments, and investigating student thinking related to molecular evolution. We conclude by providing general strategies, advice, and a novel curricular activity for teaching molecular evolution and the neutral theory of molecular evolution.

The Neutral Theory (Theory of Genetic Drift) and the Nearly Neutral Theory of Molecular Evolution are Opposite to Evolution

The Neutral theory (also known as the theory of genetic drift) means genetic drift and vice-versa. But the Nearly Neutral theory means genetic drift plus natural selection. However, genetic drift changes the gene frequency randomly and thus it is non-additive, directionless and thus valueless for evolution. Again, genetic drift works only in small populations and thus, genetic drift means small population. But small populations have to inbreed and produce homozygous organisms. Consequently, those populations suffer from various diseases and abnormalities and finally may suddenly extinct. Moreover, any homozygous organism means zero variation, mutation-genetic drift equilibrium also creates zero variation. But variation is the raw material of evolution; so, no evolution occurs by the genetic drift. So, evolutionary biologists rejected both the genetic drift and the small populations for any kind of evolution. Hence, the Neutral theory is opposite to any kind of evolution. Again, recent experiments of ecological genetics with small populations, 12 biochemical tests, and the data of the DNA sequence, fossil evidence oppose the Neutral theory. Furthermore, the rate of evolution by the Neutral theory is equal to the rate of mutation. But mutations are opposite to any kind of evolution. So, biologists rejected the Neutral theory. As the natural selection is not justified in Nearly Neutral theory; so, Neutral theory=Nearly Neutral theory. Consequently, the rejection of the Neutral theory means the rejection of the Nearly Neutral theory. Thus, both the Neutral theory and the Nearly Neutral theory are opposite to any kind of evolution.

The neutral and nearly neutral theories of molecular evolution 2

The neutral and nearly neutral theories of molecular evolution 2

The neutral and nearly neutral theories of molecular evolution 1

The neutral and nearly neutral theories of molecular evolution 1

Parallel decay of vision genes in subterranean water beetles

In the framework of neutral theory of molecular evolution, genes specific to the development and function of eyes in subterranean animals living in permanent darkness are expected to evolve by relaxed selection, ultimately becoming pseudogenes. However, definitive empirical evidence for the role of neutral processes in the loss of vision over evolutionary time remains controversial. In previous studies, we characterized an assemblage of independently-evolved water beetle (Dytiscidae) species from a subterranean archipelago in Western Australia, where parallel vision and eye loss have occurred. Using a combination of transcriptomics and exon capture, we present evidence of parallel coding sequence decay, resulting from the accumulation of frameshift mutations and premature stop codons, in eight phototransduction genes (arrestins, opsins, ninaC and transient receptor potential channel genes) in 32 subterranean species in contrast to surface species, where these genes have open reading frames. Our results provide strong evidence to support neutral evolutionary processes as a major contributing factor to the loss of phototransduction genes in subterranean animals, with the ultimate fate being the irreversible loss of a light detection system.

Non-Darwinian Molecular Biology.

With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper “Non-Darwinian Evolution”, where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura’s new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.

Rates of Protein Evolution across the Marsupial Phylogeny: Heterogeneity and Link to Life-History Traits.

Despite the importance of effective population size (Ne) in evolutionary and conservation biology, it remains unclear what factors have an impact on this quantity. The Nearly Neutral Theory of Molecular Evolution predicts a faster accumulation of deleterious mutations (and thus a higher dN/dS ratio) in populations with small Ne; thus, measuring dN/dS ratios in different groups/species can provide insight into their Ne. Here, we used an exome data set of 1,550 loci from 45 species of marsupials representing 18 of the 22 extant families, to estimate dN/dS ratios across the different branches and families of the marsupial phylogeny. We found a considerable heterogeneity in dN/dS ratios among families and species, which suggests significant differences in their Ne. Furthermore, our multivariate analyses of several life-history traits showed that dN/dS ratios (and thus Ne) are affected by body weight, body length, and weaning age.

Species ecology explains the spatial components of genetic diversity in tropical reef fishes.

Generating genomic data for 19 tropical reef fish species of the Western Indian Ocean, we investigate how species ecology influences genetic diversity patterns from local to regional scales. We distinguish between the α, β and γ components of genetic diversity, which we subsequently link to six ecological traits. We find that the α and γ components of genetic diversity are strongly correlated so that species with a high total regional genetic diversity display systematically high local diversity. The α and γ diversity components are negatively associated with species abundance recorded using underwater visual surveys and positively associated with body size. Pelagic larval duration is found to be negatively related to genetic β diversity supporting its role as a dispersal trait in marine fishes. Deviation from the neutral theory of molecular evolution motivates further effort to understand the processes shaping genetic diversity and ultimately the diversification of the exceptional diversity of tropical reef fishes.

Random Penetrance of Mutations Among Individuals: A New Type of Genetic Drift in Molecular Evolution

The determinative view of mutation penetrance is a fundamental assumption for the building of molecular evolutionary theory: individuals in the population with the same genotype have the same fitness effect. Since this view has been constantly challenged by experimental evidence, it is desirable to examine to what extent violation of this view could affect our understanding of molecular evolution. To this end, the author formulated a new theory of molecular evolution under a random model of penetrance: for any individual with the same mutational genotype, the coefficient of selection is a random variable. It follows that, in addition to the conventional N e-genetic drift (N e is the effective population size), the variance of penetrance among individuals (ε 2) represents a new type of genetic drift, coined by the ε 2-genetic drift. It has been demonstrated that these two genetic drifts together provided new insights on the nearly neutral evolution: the evolutionary rate is inversely related to the log-of-N e when the ε 2-genetic drift is nontrivial. This log-of-N e feature of ε 2-genetic drift did explain well why the d N /d S ratio (the nonsynonymous rate to the synonymous rate) in humans is only as twofold as that in mice, while the effective population size (N e) of mice is about two-magnitude larger than that of humans. It was estimated that, for the first time, the variance of random penetrance in mammalian genes was approximately ε 2 ≈ 5.89 × 10-3.

On the Unfounded Enthusiasm for Soft Selective Sweeps III: The Supervised Machine Learning Algorithm That Isn't.

In the last 15 years or so, soft selective sweep mechanisms have been catapulted from a curiosity of little evolutionary importance to a ubiquitous mechanism claimed to explain most adaptive evolution and, in some cases, most evolution. This transformation was aided by a series of articles by Daniel Schrider and Andrew Kern. Within this series, a paper entitled “Soft sweeps are the dominant mode of adaptation in the human genome” (Schrider and Kern, Mol. Biol. Evolut. 2017, 34(8), 1863–1877) attracted a great deal of attention, in particular in conjunction with another paper (Kern and Hahn, Mol. Biol. Evolut. 2018, 35(6), 1366–1371), for purporting to discredit the Neutral Theory of Molecular Evolution (Kimura 1968). Here, we address an alleged novelty in Schrider and Kern’s paper, i.e., the claim that their study involved an artificial intelligence technique called supervised machine learning (SML). SML is predicated upon the existence of a training dataset in which the correspondence between the input and output is known empirically to be true. Curiously, Schrider and Kern did not possess a training dataset of genomic segments known a priori to have evolved either neutrally or through soft or hard selective sweeps. Thus, their claim of using SML is thoroughly and utterly misleading. In the absence of legitimate training datasets, Schrider and Kern used: (1) simulations that employ many manipulatable variables and (2) a system of data cherry-picking rivaling the worst excesses in the literature. These two factors, in addition to the lack of negative controls and the irreproducibility of their results due to incomplete methodological detail, lead us to conclude that all evolutionary inferences derived from so-called SML algorithms (e.g., S/HIC) should be taken with a huge shovel of salt.

Retrotransposons and the Evolution of Genome Size in Pisum.

Here we investigate the plant population genetics of retrotransposon insertion sites in pea to find out whether genetic drift and the neutral theory of molecular evolution can account for their abundance in the pea genome. (1) We asked whether two contrasting types of pea LTR-containing retrotransposons have the frequency and age distributions consistent with the behavior of neutral alleles and whether these parameters can explain the rate of change of genome size in legumes. (2) We used the recently assembled v1a pea genome sequence to obtain data on LTR-LTR divergence from which their age can be estimated. We coupled these data to prior information on the distribution of insertion site alleles. (3) We found that the age and frequency distribution data are consistent with the neutral theory. (4) We concluded that demographic processes are the underlying cause of genome size variation in legumes.

Reflections on the Predictability of Evolution: Toward a Conceptual Framework.

SummaryEvolution is generally considered to be unpredictable because genetic variations are known to occur randomly. However, remarkable patterns of repeated convergent evolution are observed, for instance, loss of pigments by organisms living in caves. Analogous phenotypes appear in similar environments, sometimes in response to similar constraints. Alongside randomness, a certain evolutionary determinism also exists, for instance, the selection of particular phenotypes subjected to particular environmental constraints in the “evolutionary funnel.” We pursue the idea that eco-evolutionary specialization is in some way determinist. The conceptual framework of phenotypic changes entailing specialization presented in this essay explains how evolution can be predicted. We also discuss how the predictability of evolution could be tested using the case of metabolic specialization through gene losses. We also put forward that microorganisms could be key models to test and possibly make headway evolutionary predictions and knowledge about evolution.

Enrichment in conservative amino acid changes among fixed and standing missense variations in slowly evolving proteins.

The process of molecular evolution has many elements that are not yet fully understood. Evolutionary rates are known to vary among protein coding and noncoding DNAs, and most of the observed changes in amino acid or nucleotide sequences are assumed to be non-adaptive by the neutral theory of molecular evolution. However, it remains unclear whether fixed and standing missense changes in slowly evolving proteins are more or less neutral compared to those in fast evolving genes. Here, based on the evolutionary rates as inferred from identity scores between orthologs in human and Rhesus Macaques (Macaca mulatta), we found that the fraction of conservative substitutions between species was significantly higher in their slowly evolving proteins. Similar results were obtained by using four different methods of scoring conservative substitutions, including three that remove the impact of substitution probability, where conservative changes require fewer mutations. We also examined the single nucleotide polymorphisms (SNPs) by using the 1000 Genomes Project data and found that missense SNPs in slowly evolving proteins also had a higher fraction of conservative changes, especially for common SNPs, consistent with more non-conservative substitutions and hence stronger natural selection for SNPs, particularly rare ones, in fast evolving proteins. These results suggest that fixed and standing missense variants in slowly evolving proteins are more likely to be neutral.

Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock

BackgroundThe molecular clock is an important genetic tool for estimating evolutionary timescales. However, the detection of a time-dependent effect on substitution rate estimates complicates its application. It has been suggested that demographic processes could be the main cause of this confounding effect. In the present study, I propose a new algorithm for estimating the coalescent age of phylogenetically related sequences, taking into account the observed time-dependent effect on the molecular rate detected by others.ResultsBy applying this method to real human mitochondrial DNA trees with shallow and deep topologies, I obtained significantly older molecular ages for the main events of human evolution than were previously estimated. These ages are in close agreement with the most recent archaeological and paleontological records favoring the emergence of early anatomically modern humans in Africa 315 ± 34 thousand years ago (kya) and the presence of recent modern humans outside of Africa as early as 174 ± 48 thousand years ago. Furthermore, during the implementation process, I demonstrated that in a population with fluctuating sizes, the probability of fixation of a new neutral mutant depends on the effective population size, which is in better accordance with the fact that under the neutral theory of molecular evolution, the fate of a molecular mutation is mainly determined by random drift.ConclusionsI suggest that the demographic history of populations has a more decisive effect than purifying selection and/or mutational saturation on the time-dependent effect observed for the substitution rate, and I propose a new method that corrects for this effect.

The role of selection in the evolution of blindness in cave fish

AbstractThe forces driving regression of biologically functionless traits remain disputed. There is ongoing debate regarding whether selection, as opposed to disuse and neutral mutations, is involved in this process. Cave species are of particular relevance for study in this regard because in continuous darkness all traits that depend on information from light, such as eyes, dark pigmentation and certain behaviours, abruptly lose their function. Recently, strong selection driving reduction has again been proposed, which relied on modelling analyses based on assumptions such as immigration of surface alleles into the cave forms or no fitness difference existing between Astyanax surface and cave fish. The validity of these assumptions, often applied to reject neutral processes in functionless traits, is questioned in this review. Morphological variation in a trait resulting from genetic variability is typical of biologically functionless traits and is particularly notable in phylogenetically young cave species. It is the most evident indicator of loss of selection, which normally enforces uniformity to guarantee optimal functionality. Phenotypic and genotypic variability in Astyanax cave fish eyes does not derive from genetic introgression by the surface form, but from regressive mutations not being eliminated by selection. This matches well with the principles of Kimura’s neutral theory of molecular evolution.