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Saturday, April 18, 2020

Three scientists discuss junk DNA

I just found this video that was posted to YouTube on May 2019. It's produced by the University of California and it features three researchers discussing the question, "Is Most of Your DNA Junk!" The three scientists are:
  • Rusty Gage, a neuroscientist at the Salk Institute
  • Alysson Muotri, who studies brain development at the University of California, San Diego
  • Miles Wilkinson, who studies neuronal and germ cell development at the University of San Diego
None of them appear to be experts on genomes or junk DNA although one of them (Wilkinson) appears to have some knowledge of the evidence for junk DNA, although many of his explanations are garbled. What's interesting is that they emphasize the fact that some transposon-related sequences are expressed in some cells and they rely on this fact to remain skeptical of junk DNA. They also propose that excess DNA might be present in order to ensure diversity and prepare for future evolution. All three seem to be comfortable with the idea that excess DNA may be protecting the rest of the functional genome.

This is a good example of what we are up against when we try to convince scientists that most of our genome is junk.





Wednesday, April 08, 2020

Alternative splicing: function vs noise

This post is about a recent review of alternative splicing published by my colleague Ben Blencowe in the Dept. of Medical Genetics at the University of Toronto (Toronto, Ontario, Canada). (The other author is Jermej Ule of The Francis Crick Institute in London (UK).) They are strong supporters of the idea that alternative splicing is a common feature of most human genes.

I am a strong supporter of the idea that most splice variants are due to splicing errors and only a few percent of human genes undergo true alternative spicing.

This is a disagreement about the definition of "function." Is the mere existence of multiple splice variants evidence that they are biologically relevant (functional) or should we demand evidence of function—such as conservation—before accepting such a claim?

Monday, April 06, 2020

The Function Wars Part VII: Function monism vs function pluralism

This post is mostly about a recent paper published in Studies in History and Philosophy of Biol & Biomed Sci where two philosophers present their view of the function wars. They argue that the best definition of function is a weak etiological account (monism) and pluralistic accounts that include causal role (CR) definitions are mostly invalid. Weak etiological monism is the idea that sequence conservation is the best indication of function but that doesn't necessarily imply that the trait arose by natural selection (adaptation); it could have arisen by neutral processes such as constructive neutral evolution.

The paper makes several dubious claims about ENCODE that I want to discuss but first we need a little background.

Background

The ENCODE publicity campaign created a lot of controversy in 2012 because ENCODE researchers claimed that 80% of the human genome is functional. That claim conflicted with all the evidence that had accumulated up to that point in time. Based on their definition of function, the leading ENCODE researchers announced the death of junk DNA and this position was adopted by leading science writers and leading journals such as Nature and Science.

Let's be very clear about one thing. This was a SCIENTIFIC conflict over how to interpret data and evidence. The ENCODE researchers simply ignored a ton of evidence demonstrating that most of our genome is junk. Instead, they focused on the well-known facts that much of the genome is transcribed and that the genome is full of transcription factor binding sites. Neither of these facts were new and both of them had simple explanations: (1) most of the transcripts are spurious transcripts that have nothing to do with function, and (2) random non-functional transcription factor binding sites are expected from our knowledge of DNA binding proteins. The ENCODE researchers ignored these explanations and attributed function to all transcripts and all transcription factor binding sites. That's why they announced that 80% of the genome is functional.