Overcoming challenges and dogmas to understand the functions of pseudogenes - review

"In terms of junk DNA, we don’t use that term anymore because I think it was pretty much a case of hubris to imagine that we could dispense with any part of the genome, as if we knew enough to say it wasn’t functional. … Most of the genome that we used to think was there for spacer turns out to be doing stuff.” - Francis Collins, head of the Human Genome Project

The journal article "Overcoming challenges and dogmas to understand the functions of pseudogenes" by Cheetham, Faulkner, and Dinger (2020) discusses the growing body of evidence that pseudogenes play important biological roles, despite their previous classification as "junk DNA." The authors argue that this misclassification is due in part to the pejorative inference of the term "pseudogene" itself, as well as to the limitations of traditional genome annotation practices.

Pseudogenes are defined as regions of the genome that contain defective copies of genes. They can arise through a variety of mechanisms, such as gene duplication, retrotransposition, and mutation. While pseudogenes were once thought to be non-functional, it is now clear that many of them play important roles in gene regulation, cell signaling, and other biological processes.

The authors of the article discuss several challenges and dogmas that have hindered the study of pseudogenes. One challenge is that pseudogenes are often difficult to identify and distinguish from functional genes. This is because pseudogenes can share high sequence similarity with functional genes, and they may even be transcribed into RNA. However, pseudogenes typically lack key features of functional genes, such as open reading frames and promoter sequences.

Another challenge is that pseudogenes are often excluded from functional studies. This is due in part to the assumption that pseudogenes are non-functional, as well as to the difficulty of designing experiments to specifically test the function of pseudogenes. However, the authors argue that it is important to study pseudogenes in order to understand their full range of biological functions.

The authors also discuss several dogmas that have prevented scientists from fully appreciating the importance of pseudogenes. One dogma is that pseudogenes are simply evolutionary relics that have no function. However, there is now evidence that many pseudogenes have been under purifying selection, suggesting that they retain important functions.

Another dogma is that pseudogenes are only important for gene regulation. However, pseudogenes have also been shown to play roles in cell signaling, protein-protein interactions, and other biological processes.

The authors conclude by calling for a more objective reassessment of pseudogenes. They argue that pseudogenes have been unfairly dismissed as junk DNA, and that their study has the potential to reveal valuable insights into genome function and evolution.

The article also discusses several emerging technologies that are simplifying the study of pseudogenes. For example, next-generation sequencing and RNA sequencing technologies are making it easier to identify and characterize pseudogenes. In addition, new computational methods are being developed to predict the function of pseudogenes.

The authors believe that these emerging technologies will lead to a significant increase in our understanding of pseudogenes and their biological roles. They argue that it is time to move beyond the dogma that pseudogenes are junk DNA and to embrace the new era of pseudogene research.

The article challenges neo darwinism in two main ways:

1. It suggests that pseudogenes, which are often considered to be "junk DNA," may actually play important functional roles in the genome. This challenges the neo darwinian view that evolution is driven primarily by selection for beneficial mutations in protein-coding genes.

2. It highlights the limitations of genome annotation practices, which often misclassify pseudogenes as non-functional. This suggests that the number of functional pseudogenes in the genome may be much larger than previously thought, and that our understanding of gene function is incomplete.

Neo Darwinism is a theory of evolution that combines Darwin's theory of natural selection with Mendelian inheritance. It is the prevailing theory of evolution in biology today. Neo Darwinists believe that evolution is driven by natural selection, which is the differential survival and reproduction of individuals with favorable traits. Natural selection is thought to act on random mutations in protein-coding genes, which are genes that encode proteins. Pseudogenes fall outside of neodarwinismo as they do not directly code for proteins for natural selection to act. Ergo they were labeled as "Junk."

Pseudogenes are defined as regions of the genome that contain defective copies of protein-coding genes. They are often thought to be non-functional, as they contain mutations that prevent them from encoding functional proteins. However, a growing body of evidence suggests that pseudogenes may actually play important roles in gene regulation and other cellular processes.

The authors point out that pseudogenes are found in all forms of life and that they are often highly conserved, suggesting that they are under selective pressure. This suggests that pseudogenes must be providing some kind of evolutionary benefit unlike what neo darwinism predicted.

Genome annotation practices are often biased against pseudogenes, as they are designed to identify protein-coding genes. This means that many pseudogenes are misclassified as non-functional.

The Cheetham et al. article concludes by calling for a more open-minded approach to the study of pseudogenes. If pseudogenes are found to play important functional roles in the genome, this would challenge the neo darwinian view that evolution is driven primarily by selection for beneficial mutations in protein-coding genes. It would suggest that other genomic elements, such as pseudogenes, may also play a role in evolution.

Additionally, if genome annotation practices are misclassifying many pseudogenes as non-functional, this suggests that our understanding of gene function is incomplete. This could have implications for our understanding of disease and other biological processes.

Overall, the Cheetham et al. article is an important contribution to the growing field of pseudogene research. It challenges neo darwinism and suggests that we need to rethink our understanding of gene function.