BGC the Achilles’ heel of our genome


The article "Adaptation or biased gene conversion? Extending the null hypothesis of molecular evolution" by Nicolas Galtier and Laurent Duret discusses the two main mechanisms that can lead to accelerated rates of molecular evolution: natural selection and biased gene conversion.

Natural selection occurs when there is a differential fitness between individuals with different genotypes. This can lead to the fixation of beneficial mutations, which can cause the rate of evolution of a particular sequence to increase.

Biased gene conversion is a process in which homologous DNA sequences are exchanged, resulting in the transfer of genetic material from one sequence to another. This can also lead to accelerated rates of evolution, especially in regions of the genome that are highly conserved.

The authors argue that the null hypothesis of molecular evolution should be extended to include biased gene conversion as a possible explanation for accelerated rates of evolution. They present several lines of evidence that support this hypothesis, including:

  • The observation that many regions of the human genome that are thought to be under positive selection are also regions that are highly GC-rich. This suggests that natural selection mimics biased gene conversion which is really playing the role in the evolution of these regions.

  • The observation that biased gene conversion is more likely to occur between sequences that are highly similar. This suggests that it may be more likely to occur in regions of the genome that are highly conserved.

  • The observation that biased gene conversion can be influenced by factors such as recombination rate and DNA repair mechanisms. This suggests that it may be more likely to occur in some species or populations than others.

The authors conclude that biased gene conversion is a "non-negligible" factor in molecular evolution, and that it should be considered alongside natural selection when interpreting patterns of molecular evolution.

In addition to the evidence presented by Galtier and Duret, there is a growing body of research that supports the role of biased gene conversion in molecular evolution. For example, a study by Zhang et al. (2012) found that biased gene conversion was more likely to occur in regions of the genome that were under positive selection. Another study by Chen et al. (2013) found that biased gene conversion could contribute to the evolution of new genes.

While the role of biased gene conversion in molecular evolution is still not fully understood, it is clear that it is a significant factor that can influence the rate and direction of evolution. By understanding the mechanisms of biased gene conversion, we can better understand the processes that shape the genetic diversity of life on Earth.

Here are some additional thoughts on the article:

  • The authors argue that biased gene conversion can be difficult to distinguish from natural selection. This is because both processes can lead to accelerated rates of evolution. However, there are some factors that can help to distinguish between the two processes. For example, biased gene conversion is more likely to occur between sequences that are highly similar, while natural selection is more likely to occur between sequences that are different.

  • The authors argue that biased gene conversion can be a "double-edged sword". On the one hand, it can help to fix beneficial mutations, which can lead to adaptation. On the other hand, it can also lead to the fixation of harmful mutations, which can lead to genetic disorders.

  • The authors argue that the study of biased gene conversion is still in its early stages. However, they believe that it is a promising area of research that could help us to better understand the mechanisms of molecular evolution.

Overall, the article by Galtier and Duret is a valuable contribution to the field of molecular evolution. It provides a comprehensive overview of the mechanisms of biased gene conversion and discusses the evidence that supports its role in molecular evolution. The article also raises some important questions about the potential consequences of biased gene conversion for adaptation and genetic disorders.

Article Snippets

The analysis of evolutionary rates is a popular approach to characterizing the effect of natural selection at the molecular level.

Sequences contributing to species adaptation are expected to evolve faster than nonfunctional sequences because favourable mutations have a higher fixation probability than neutral ones.

Such an accelerated rate of evolution might be due to factors other than natural selection, in particular GC-biased gene conversion.

This is true of neutral sequences, but also of constrained sequences

Several criteria can discriminate between the natural selection and biased gene conversion models.

These criteria suggest that the recently reported human accelerated regions are most likely the result of biased gene conversion.

We argue that these regions, far from contributing to human adaptation, might represent the Achilles’ heel of our genome.

Most functional sequences are subject to negative (purifying) selection (see Glossary) and hence can be recognized because they evolve less rapidly than neutral sequences.

this approach only identifies functional elements that are conserved among species, whereas there is a major interest in detecting the elements that evolved toward new functions in some specific lineages and contributed to species adaptation.

adaptation is invoked when the nonsynonymous substitution rate exceeds the (presumably neutral) synonymous one

Forces other than natural selection, however, can lead to an increased nucleotide substitution rate

From a population genetics point of view, the BGC meiotic drive is essentially equivalent to directional selection

Under the BGC model, AT → GC mutations have a higher probability to be transmitted to the next generation, and eventually fixed, than is the case for other mutations (GC → AT, AT → TA or GC → CG).

an episode of BGC should therefore result in an increased substitution rate,

BGC can theoretically overcome purifying selection and lead to the fixation of deleterious AT → GC mutations

BGC, similarly to adaptation, can result in a sudden increase in substitution rate in nonfunctional, but also in functional, regions

several aspects of the evolution of HARs seem to be consistent with the BGC model,

substitutions that have accumulated in the human lineage are mostly AT → GC changes

BGC substitution hotspots: genomic Achilles’ heel

BGC can lead to lineage-specific increases in substitution rate in functional sequences in the absence of adaptation

Moreover, several features of the HARs seem to be more consistent with the BGC model than with selective scenarios.

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