Phenotypic Plasticity and Macroevolution: Ka/Ks ratios no longer support Macroevolution studies

Phenotypic plasticity can resemble macroevolution in many ways:

Phenotypic plasticity:

• The ability of an organism to change its traits (phenotype) in response to environmental conditions.

• Examples: chameleons changing color, tadpoles developing into legs, plants growing taller in the shade. Darwin's finches. Cichlid fish changes.

Macroevolution:

• Proposes the emergence of new species and major changes in existing ones over long periods.

Superficial similarities:

• Phenotypic plasticity can lead to diverse appearances within a single species.

• Both are promised to be adaptive, allowing organisms to survive and reproduce in different environments.

• While phenotypic plasticity can create temporary variation that is passed on.

• However, plasticity can play a supportive role in evolution by:

• Allowing populations to adapt to changing environments before genetic changes occur.

• Leading to genetic assimilation, where plastic traits become fixed in the genome over time.

Phenotypic plasticity can cause long-term changes, in several ways:

Direct Long-Term Effects:

• Physiological or morphological changes: In some cases, the plastic response itself directly alters the organism's structure or function in a long-lasting way. For example, tadpoles exposed to a predator cue may develop larger tails, which permanently impacts their swimming ability.

• Behavioral conditioning: Learned behaviors through experience can have long-term impacts on an individual's survival and fitness, affecting areas like foraging strategies, habitat selection, and predator avoidance.

Indirect Long-Term Effects:

• Evolutionary consequences: When plastic responses consistently increase individual fitness within a certain environment epigenetic canalization favors genes that predispose those responses. Over generations, this can lead to genetic assimilation, where the plastic trait becomes genetically encoded and no longer requires environmental triggers.

• Transgenerational effects: In some cases, environmental cues experienced by parents can influence the development of their offspring, even without direct genetic inheritance. This phenomenon, known as transgenerational plasticity, can have long-term consequences for populations.

Important Nuances:

• Duration of Change: The "long-term" aspect is relative. For short-lived organisms, a few generations might be considered long-term, while for others, it could span hundreds or even thousands of years.

• Reversibility: Some plastic changes are temporary and reversible, while others are more permanent. This depends on the specific response and the organism involved.

Examples:

• Lizards adapting to different temperatures: Lizards in cooler environments can adjust their metabolic rate and body color to better conserve heat, impacting their long-term survival and potentially leading to genetic assimilation.

• Plants adjusting to nutrient availability: Plants in nutrient-poor environments may grow smaller root systems, a plastic response that can have lasting effects on their water and nutrient uptake.

• Birds learning migration routes: Young birds learn migration routes from their parents, a form of plasticity that helps them navigate vast distances across generations.

Overall, phenotypic plasticity is a powerful mechanism that allows organisms to adapt to their environment, with the potential for long-term consequences at individual, population, and even evolutionary levels. It can mimic macroevolution and in time the difference will be sorted out.

Macroevolution studies rely on Comparative Genomics not the new field of Comparative Epigenomics like with phenotypic plasticity

Comparing the similarity of the DNA of different organism is used in macroevolution and tries to establish Darwin’s common ancestry. This can lead to questionable results. For example, a man shares 94% the same DNA as a dog. So does this illustration apply?

Or what of a Daffodil?

Therefore until the field of comparative epigenetics is mature, chasing down common Ancestry and macroevolution is problematic.

Bees are a great example of comparative epigenetics. The have the same genes but remarkably different phenotypes. The same applies to identical twins. One may have schizophrenia or one heart disease.

Macroevolution studies relies heavily on Ka/Ks ratios

Studies on macroevolution have heavily utilized Ka/Ks ratios as a tool for understanding the evolutionary forces shaping protein-coding genes. Here's a breakdown of how it works:

What is a Ka/Ks ratio?

The Ka/Ks ratio, also known as the ω or dN/dS ratio, compares the rates of nonsynonymous (Ka) and synonymous (Ks) substitutions in a gene sequence over time.

• Nonsynonymous substitutions: These changes alter the amino acid sequence of a protein, potentially affecting its function.

• Synonymous substitutions: These changes occur in DNA codons that code for the same amino acid, so they don't affect the protein's function.

Since synonymous substitutions are generally considered neutral (not under selection pressure), they serve as a reference for the expected rate of mutations in the absence of selection. 

By comparing the rates of Ka and Ks, scientist used to infer the type and strength of selection acting on a gene:

• Ka/Ks > 1: This indicates positive selection, meaning beneficial mutations are being favored, leading to faster amino acid evolution.

• Ka/Ks < 1: This indicates purifying selection, where harmful mutations are removed, resulting in slower amino acid evolution.

• Ka/Ks = 1: This suggests neutral evolution, where mutations are neither favored nor disfavored.

How are Ka/Ks ratios used in macroevolution studies?

By analyzing Ka/Ks ratios across diverse sets of genes and species, researchers can gain insights into various aspects of macroevolution:

• Identifying genes under positive selection: Genes with consistently high Ka/Ks ratios across different lineages could be evolving rapidly due to adaptation to new environments or functions. This helps researchers pinpoint genes potentially involved in key evolutionary innovations.

• Estimating rates of molecular evolution: Ka/Ks ratios can be used to calibrate molecular clocks, which estimate the time elapsed since two species diverged based on accumulated mutations. This is crucial for reconstructing phylogenetic trees and understanding the timing of major evolutionary events.

• Detecting adaptive radiations: Periods of rapid diversification often involve positive selection on specific genes. Analyzing Ka/Ks ratios across species within a radiation can reveal signatures of such selection and shed light on the evolutionary mechanisms driving diversification.

Challenging the Silent Dogma: A Paradigm Shift in Mutation Neutrality?

Two recent articles have thrown a sinking  curveball at a foundational principle of genetics: the assumption that synonymous mutations, those changing DNA code without altering amino acid sequence, are selectively neutral. This notion has underpinned numerous evolutionary studies, relying on the "silent" nature of synonymous mutations to isolate specific signals. However, the papers "Synonymous mutations in representative yeast genes are mostly strongly non-neutral" (Shen et al., 2022) and the paper "Nonsynonymous Synonymous Variants Demand for a Paradigm Shift in Genetics" (Vihinen, 2023) propose a radical challenge, arguing that a large proportion of synonymous mutations have significant functional consequences.

From Neutrality to Nuance: The Studies and Their Claims

Shen et al. (2022) analyzed thousands of synonymous mutations in 21 yeast genes across varying environments. They observed a surprising finding: 75% of these mutations significantly reduced fitness, with effects comparable to non-synonymous mutations. This directly contradicts the established view of their neutrality and opens a Pandora's box of potential implications.

Vihinen (2023) builds upon this, arguing that the traditional binary classification of mutations solely as synonymous or non-synonymous might be overly simplistic. He emphasizes the need to consider additional layers of complexity, such as:

• Unsense substitutions: Even within synonymous mutations, misinterpretations during transcription or translation can create unintended stop codons, rendering them highly detrimental.

• Altered mRNA folding and stability: Synonymous mutations can subtly affect mRNA structure, impacting its stability, translation efficiency, and ultimately, protein production.

• Epigenetic effects: Mutations can influence DNA methylation or chromatin structure, indirectly affecting gene expression beyond the protein sequence itself.

These points highlight the multifaceted nature of mutation effects, suggesting that the "silent" label for synonymous mutations is a significant oversimplification.

Why didn't 60 years of scientific studies show this? Simply because the CRISPR mechanism was only recently discovered. CRISPR was able to precisely mutate as never before synonymous substitution and measure actual “fitness” at the DNA level.

Potential Paradigm Shift and Its Ripples

If these findings hold true across diverse genes and organisms, the implications could be far-reaching:

• Re-evaluation of Ka/Ks: The traditional Ka/Ks ratio, is a cornerstone metric for evolutionary studies including macroevolution. They rely on the assumption of synonymous mutations being selectively neutral. If this assumption is challenged, estimates of evolutionary rates, divergence times, and selection pressures need significant revision.

• Mutation rate and pattern: The contribution of synonymous mutations to mutation rates and patterns might be significantly larger than previously thought, impacting evolutionary inferences drawn from these metrics.

Towards a More Nuanced Understanding: The Road Ahead

A full paradigm shift is called for. These studies undeniably open a new chapter in our understanding of mutations. They highlight the need to move beyond the simplistic binary view (nonsynonymous & synonymous) and embrace a more nuanced perspective that incorporates diverse mechanisms and their potential impact on evolution and disease. 

Conclusion 

Macroevolution studies were largely based on Ka/Ks studies which now are significantly challenged. Whereas epigenetic phenotypic plasticity studies are surpassing this approach with more complete epigenetic information in concert with the genome. And to think a billion year old virus protector in bacteria challenged our view of evolution.