Short Tandem Repeats Bind Transcription Factors to Tune Eukaryotic Gene Expression: A Challenge to Neodarwinism

Introduction

Short tandem repeats (STRs) are sequences of DNA that are made up of repeated units of two to six nucleotides. STRs are found throughout the genome, but they are particularly enriched in cis-regulatory elements, which are DNA sequences that control the expression of genes.

In order to form an inverted repeat, two mutations would need to occur in the same gene, at the same location, but in opposite directions. This is a very unlikely event, and it is estimated to occur only once in every billion years.

However, inverted repeats are found in 5% of organisms DNA  suggesting that they are not simply the result of neo darwinian random mutations.

How STRs Bind Transcription Factors

Transcription factors are proteins that bind to DNA and regulate the transcription of genes. STRs can bind to transcription factors directly, and this binding can modulate the transcription factor's affinity for DNA and its rate of association with DNA.

STRs Can Tune Eukaryotic Gene Expression

By binding to transcription factors, STRs can tune the expression of eukaryotic genes. For example, STRs can increase or decrease the expression of a gene, or they can make the expression of a gene more or less responsive to environmental cues.

STRs Challenge Neodarwinism

Neodarwinism is the theory of evolution that is based on the principles of natural selection and genetic variation. Neodarwinism holds that all genetic variation is random, and that natural selection acts on this variation to produce new species and adaptations.

However, the discovery that STRs can bind to transcription factors and tune gene expression suggests that not all genetic variation is random. STRs are often polymorphic, meaning that they can vary in length from individual to individual. These variations in STR length can have a significant impact on gene expression.

For example, a study published in the journal Science in 2022 found that STRs can modulate transcription factor binding and gene expression by up to 70-fold. This suggests that STRs can play a major role in shaping the diversity of gene expression in eukaryotic populations.

The fact that STRs can bind to transcription factors and tune gene expression also challenges the neodarwinist view of natural selection. Neodarwinism holds that natural selection acts on random genetic variation to produce new species and adaptations. However, STRs are not random, but instead have specific functions in regulating gene expression to produce new adaptations outside of NeoDarwinism.

Examples of STR-Mediated Gene Regulation

There are many examples of STR-mediated gene regulation in eukaryotes. For example, STRs have been shown to regulate gene expression in a variety of human diseases, including cancer, autism, and schizophrenia.

STRs have also been shown to play a role in the evolution of new species. For example, a study published in the journal Nature Genetics in 2021 found that STR variation is associated with the evolution of beak shape in Darwin's finches.

Conclusion

The discovery that STRs can bind to transcription factors and tune gene expression challenges the neodarwinist view of evolution. Neodarwinism holds that all genetic variation is random, and that natural selection acts on this variation to produce new species and adaptations. However, the fact that STRs have specific functions in regulating gene expression suggests that not all genetic variation is random.

More on How STRs Challenge Neodarwinism

One of the key challenges that STRs pose to neodarwinism is the fact that they can be rapidly amplified or deleted from the genome. This is because STRs are often located in repetitive regions of the genome, which are prone to recombination errors.

The rapid amplification or deletion of STRs can lead to significant changes in gene expression. For example, a study published in the journal Nature Genetics in 2018 found that the amplification of an STR in the FMR1 gene is responsible for the neurodevelopmental disorder Fragile X syndrome.

The ability of STRs to be rapidly amplified or deleted from the genome suggests that they could play a role in rapid adaptation to environmental changes outside of neodarwinism. For example, a study published in the journal Proceedings of the National Academy of Sciences in 2019 found that the rapid deletion of an STR in the KITLG gene is associated with the evolution of white fur in Arctic foxes.

Another challenge that STRs pose to neodarwinism is the fact that they can be epigenetically regulated. Epigenetic regulation is the process by which gene expression is regulated without changing the DNA sequence itself. Sequence change is a axiom of NeoDarwinism.

STRs can be epigenetically regulated by DNA methylation and histone modifications. These epigenetic modifications can alter the way that transcription factors bind to STRs, and this can have a significant impact on gene expression.

The epigenetic regulation of STRs suggests that they play a major role in the inheritance of acquired traits without NeoDarwinism.

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