"A century of bias in genetics and evolution" Nature Journal review, aka Natural Selection exit stage left.

Epigenetics, codon bias, and GC bias are all non-Darwinian mechanisms that can mimic natural selection. This raises the question: were we really seeing natural selection all this time or these other factors? They have definite mechanisms where natural selection is more illusory. This stands to challenge 170 of evolution. In place we have "designed" teleological mechanisms.

• Epigenetics is the study of changes in gene expression that are not caused by changes in the DNA sequence. These changes can be inherited, and they can affect how a gene is expressed, even if the DNA sequence of the gene is unchanged. Epigenetic changes can be caused by environmental factors, such as diet, stress, and exposure to toxins.

• Codon bias is the uneven use of synonymous codons in a genome. Synonymous codons are different codons that code for the same amino acid. Codon bias can be caused by a number of factors, including the abundance of tRNA molecules that can translate each codon, the efficiency of translation, and the stability of the resulting protein.

• GC bias is the uneven distribution of guanine and cytosine (GC) nucleotides in a genome. GC-rich regions are more stable than AT-rich regions, so GC bias can affect the expression of genes.

All of these non-Darwinian mechanisms can affect the phenotype of an organism, even if the DNA sequence of the organism is unchanged. This means that they can mimic natural selection, and they can lead to the evolution of new traits.

However, it is important to note that non-Darwinian mechanisms are not the same as natural selection. Natural selection requires that there be variation in a population, and that there be differential survival and reproduction of individuals with different traits. Non-Darwinian mechanisms can cause variation in a population without natural selection.

What's natural selection to do? It can run but it can not hide.

The article "A century of bias in genetics and evolution" by Laurence D. Hurst, published in Nature in 2019, reviews the history of research on biased transmission of genetic information. Hurst argues that an initial focus on unbiased transmission in the early 20th century has given way to a growing interest in biased transmission in the 21st century. This shift in focus is due in part to technological advances that have made it possible to detect even very weak biases.

Hurst identifies three main types of biased transmission:

• Segregation distortion: This occurs when one allele is more likely to be passed on to offspring than another allele, even when the two alleles are equally frequent in the population. Segregation distortion can be caused by a variety of factors, including genetic hitchhiking, meiotic drive, and cytoplasmic inheritance.

• Gene conversion: This is a process that results in the replacement of one allele with another allele at a nearby locus. Gene conversion can be biased, such that one allele is more likely to be converted than another. This bias can be caused by a variety of factors, including the physical distance between the two loci, the sequence similarity of the two alleles, and the presence of regulatory elements.

• Parental imprinting: This is a phenomenon in which the expression of a gene is influenced by the parent from which it was inherited. Imprinting can be caused by epigenetic modifications to the DNA, such as DNA methylation.

Hurst argues that biased transmission can have a significant impact on evolution. For example, segregation distortion can lead to the rapid spread of deleterious alleles, while gene conversion can lead to the rapid evolution of new genes. Hurst also argues that biased transmission can help to explain a variety of biological phenomena, such as the evolution of sex, the existence of genetic diseases, and the structure of the human genome.

The article "A century of bias in genetics and evolution" provides a comprehensive overview of the field of biased transmission. Hurst's work has helped to raise awareness of the importance of biased transmission in evolution, and it has inspired further research into this important area.

Here are some additional thoughts on the article:

• Hurst's work highlights the importance of considering all possible sources of bias when studying evolution. In the past, many evolutionary biologists have assumed that genetic transmission is unbiased. However, Hurst's work shows that this assumption is often not valid.

• Hurst's work also shows that biased transmission can have a significant impact on evolution. For example, it can lead to the rapid spread of deleterious alleles, the rapid evolution of new genes, and the evolution of complex biological traits.

• Hurst's work is an important contribution to our understanding of evolution. It provides a new perspective on how evolution works, and it opens up new avenues for research.

Article snippets

Mendel proposed that the heritable material is particulate and that transmission of alleles is unbiased.

More recently, the selectionist–neutralist duopoly was broken by the realisation that biased gene conversion can explain phenomena such as mammalian isochore structures

Understanding of the role of bias in transmission is, I suggest, a helpful way of explaining the relationship between the two, so overcoming psychological biases that can be an impediment to learning owing to cognitive dissonance

Fitness isn’t so important if inheritance isn’t Mendelian

natural selection operating on organismal fitness would be just one player in the game.

Typically, if you construct a mathematical model, you look to see how broad the parameter space is for your model to work.

If this space is small, then your model is looking a bit flimsy.

Indeed, I know of no other model in science of any flavour where such an important body of theory starts by presuming the one value of a parameter necessary for the models to work.

But this is what the vast bulk of population genetics does and is the cornerstone of why we think selection (organismic fitness) is so important

The slow rise of non-Mendelian genetics

Gershenson’s analysis of an X-linked meiotic drive gene

He argues that “since it exists in the natural population it is probably useful, or at least harmless for the evolution of the given Species”.

This is the usual backwards Darwinian logic—if it is observed it must be beneficial.

The best evidence we have from mammals and birds is that, indeed, gene conversion can be biased in favour of GC alleles over orthologous AT alleles.

but hotspots can exist

The population genetics of biased gene conversion is similar to that of meiotic drive (Gutz and Leslie 1976), excepting that drive typically happens in every drive heterozygote, while biased gene conversion requires the conversion tract, and heteroduplex, to form around the GC:AT heterozygous site.

Importantly, this process of biased transmission provides our best current explanation as to why our genome has blocks of high GC and others with low GC (isochores) and why non-recombining chromosomes and centromeres are AT rich

The high GC domains are crucially domains of high recombination

AT rich regions, by contrast, are low recombination domains in which there is no evidence for a fixation bias and appear to be closer to mutational equilibrium, mutation being GC->AT biased

Thus, the high GC domains are not explained by mutation bias and drift (i.e. not the neutralist model)

Selectionist models, that are consistent with this fixation bias, are in principle hard to discriminate from a biased gene conversion model

Such weak selection models suggest that domains of high GC may simply reflect a greater efficiency of selection in domains of high recombination (Charlesworth 1994b) owing the reduced Hill-Robertson interference.

A weakness of many such models is that they typically do not specify why, exactly, an AT->GC SNP is selectively favoured, even in non-coding DNA far from gene bodies, they just presume that it could be.

In this regard, the model could equally well be consistent with a model supposing that recombination was associated with domains of low GC

It is also questionable as to whether selection can explain the strength of any GC-recombination correlation

Biased gene conversion, by contrast provides a better specified and more parsimonious model.

It requires no increased genetic load, explains a fixation bias, why this bias is associated with domains of high recombination, and importantly, why high recombination is associated with high GC, this being the observed direction of the transmission bias

It also provides a parsimonious explanation as to why GC content variation is declining in some mammals

More generally, one can indeed argue that given the observed gene conversion bias, the evolution of isochores becomes near inevitable so long as recombination is itself concentrated in certain genomic domains

Thus, what was pitched as the ultimate neutralist–selectionist battle (Eyre-Walker and Hurst 2001), is most likely resolved by a third class of explanation: biased transmission

But the bearers of the advantaged allele can be at a disadvantage and the maths does not resemble drift so much as drive

However, BGC is different from any mode of selection that requires the allele to be advantageous to the bearer of the allele, be that bearer a haploid gamete or the diploid parent/progeny

As regards the neutralist–selectionist debate I think it best to consider BGC neither neutralist nor selectionist, and hence that it best considered a third class of model.

In many species the extent of the bias in biased gene conversion is strong, with ~ 70:30 bias not being unusual at the site of conversion events.

A bias as small as 50.03:49.97 could in a selectionist framework be considered an allele under strong selection,

While absence of bias in segregation ratios was key to the understanding that selection as a force can matter, a century later focus has to some degree shifted to the possibility that biased segregation matters, especially for processes like biased gene conversion.

The centrality of transmission bias (or lack thereof) to understanding the fate of alleles also underpins the more general notion that to understand evolution, we need to understand the underlying transmission genetics, which in turn requires us to understand molecular genetics (for example the molecular biology of gene conversion).

Evolutionary biologists have much to learn from really understanding the black box of molecular genetics.

The example of biased gene conversion is a case in point.

This would be an example where the assumption that one can just study phenotype and ignore the underlying genetics—the phenotypic gambit (Grafen 2014)—fails

What in broader scope are we to make of this history?

And yet, in UK schools the two subjects are taught as distinct entities with no connection (selection alone matters and the phenotypic gambit is implicitly made).

Teaching the importance of biased and unbiased transmission may then be an effective means to breakdown psychological biases that cause cognitive dissonance so impeding learning about evolution

https://www.nature.com/articles/s41437-019-0194-2