Tuesday, October 17, 2023

Norman Johnson reviews my book in "Evolution" journal

A junk-filled genome
Review of: What’s In Your Genome? 90% of Your Genome Is Junk, by Laurence A. Moran, 2023. University of Toronto Press. 392 pp. ISBN: 9781487508593
Norman A Johnson
Evolution, qpad176, [10.1093/evolut/qpad176]

"The subject matter in this book is not easy. Molecular biologists might well be challenged by the population genetics theory, while the biochemistry details may vex evolutionary biologists. Moran does an excellent job at presenting both of these aspects. I am also glad that he provided a historical perspective, showing that many of the current debates have a long history.

In the Preface, Moran states that he was motivated to write this book in part due to what he views as failures in science communication regarding the nature of the genome. He reminds us about the importance of accuracy in science communication: “No matter how good your style, if the substance of what you are communicating is flawed, then you are not a good science communicator” (xiii). Narratives are useful in communicating science, but when they (or the hype) get in the way of telling the truth, the science, and the science communication suffer."


Monday, October 16, 2023

Stephen Meyer lies about scientists working on evolutionary theory

I know Stephen Meyer and I have discussed his views on creationism many times. Some of the issues he raises are quite interesting and they aren't easy to refute. In this video from 2020, he presents two standard creationist objections to evolution: the Cambrian explosion, and the probability of evolving a gene.1

Sunday, October 15, 2023

Only 10.7% of the human genome is conserved

The Zoonomia project aligned the genome sequences of 240 mammalian species and determined that only 10.7% of the human genome is conserved. This is consistent with the idea that about 90% of our genome is junk.

The April 28, 2023 issue of science contains eleven papers reporting the results of a massive study comparing the genomes of 240 mammalian species. The issue also contains a couple of "Perspectives" that comment on the work.

On the conservation of regulatory sites in the human genome

There are a million potential transcription regulatory sites in the human genome. How many of these function as true regulatory sites?

One of the important questions about the human genome concerns how gene expression is regulated. The main controversy is over the number of functional regulatory sites and how that relates to abundant junk DNA. Here's how one group addresses the problem by looking at the conservation of regulatory sites in mammals. Sequence conservation is best genomics proxy for identifying functional sites.

Andrews, G., Fan, K., Pratt, H.E., Phalke, N., Zoonomia Consortium, Karlsson, E.K., Lindblad-Toh, K., Gazal, S., Moore, J.E. and Weng, Z. (2023) Mammalian evolution of human cis-regulatory elements and transcription factor binding sites. Science 380:eabn7930. [doi: 10.1126/science.abn7930]

Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.6 million human transcription factor binding sites (TFBSs). We identified 439,461 cCREs and 2,024,062 TFBSs under evolutionary constraint. Genes near constrained elements perform fundamental cellular processes, whereas genes near primate-specific elements are involved in environmental interaction, including odor perception and immune response. About 20% of TFBSs are transposable element–derived and exhibit intricate patterns of gains and losses during primate evolution whereas sequence variants associated with complex traits are enriched in constrained TFBSs. Our annotations illuminate the regulatory functions of the human genome.

The authors introduce the issue by pointing out two different views of functional regulatory sites. First, there's the ENCODE view, which maps the binding sites of 1600 transcription factors and the associated methylation and histone modification patterns. This analysis creates a database of almost one million candidate cis-regulatory elements (cCREs). Second, there's the evolutionary perspective, which looks at conservation of regulatory sites as the prime indicator of function. Only a fraction of candidate sites are conserved. Does this mean that most of the cCREs are not functional?

Andrews et al. set out to identify all of the cCRE's and transcription factor binding sites (TFBSs) that show evidence of conservation using an alignment of 241 mammalian genomes from the Zoonomia database and a program called phyloP.

They began with more than 920,000 human cCREs from the ENCODE Consortium results. Their results indicate that 47.5% of all CREs are highly conserved because they align to almost all of the 240 non-human mammalian genomes. (I have no idea how the phyloP program calculates "conservation.") That means approximately 439,000 sites that are likely to be genuine regulatory sequences covering 4% of the human genome. If there are 25,000 genes then this means that each gene requires about 17 regulatory sequences.

The next step was to examine 15.6 million TFBSs with a median length of 10 bp covering 5.7% of the human genome. They classified 32.5% of these sequences as highly conserved using the mysterious phyloP program. That means about 5.1 million functional transcription factor binding sites, but later on they reduce this to 2 million covering 0.8% of the genome. This is equivalent to an average of 80 per gene.

I don't believe that the authors have identified functional sites. There is no critical analysis of the results or the methodology and no attempt to rationalize the extraordinary claim that every gene requires so many regulatory sites. About 10,000 genes are regular housekeeping genes, such as those encoding the standard metabolic enzymes, and it's difficult to imagine that those genes require such complex regulation.


Image credit: ©Laurence A. Moran, What's in Your Genome?, p. 289.

Saturday, October 14, 2023

The number of splice variants in a species correlates inversely with the population size - what does that mean?

Most of the genes in eukaryotes contain introns that are removed by splicing during processing of the primary transcript. In some cases the gene produces two different functional RNAs due to differential splicing of the introns. If the product is mRNA then two different versions of the protein can be made as shown in the figure from my book What's in Your Genome? This mechanism is known as alternative splicing.

True alternative splicing is rare—less than 5% of all genes are alternatively spliced.1 However, when you analyze all of the transcripts in a tissue you will invariably detect many transcripts from junk DNA and many low abundance splice variants. Those transcripts and splice variants are due to transcription errors and splicing errors. Splicing errors arise from the presence of weak splice sites that are occasionally recognized by the normal spliceosome or by the splice factors responsible for true alternative splicing.

Tuesday, October 10, 2023

How many genes in the human genome (2023)?

The latest summary of the number of genes in the human genome gets the number of protein-coding genes correct but their estimate of the number of known non-coding genes is far too high.

In order to have a meaningful discussion about molecular genes, we have to agree on the definition of a molecular gene. I support the following definition (see What Is a Gene?).

Monday, October 09, 2023

Intelligent Design Creationism and irreducible complexity

Jonathan McLatchie is an Intelligent Design Creationist who now blogs frequently on the Discovery website Evolution News [sic]. His latest post is How NOT to Argue Against Irreducible Complexity where he defends the claim that the human male reproductive apparatus is irreducibly complex and therefore must be a product of intelligent design.

You can read the post yourself to see how ID proponents argue. I want to make another point.

McLatchie thinks that the irreducible complexity argument is very powerful evidence for intelligent design. He writes,

The argument from irreducible complexity against evolution and for design has always held strong intuitive appeal for me, and it has hence become my argument of choice in discussions about the scientific merits of evolution versus design.

Let's look at the logic of the argument from irreducible complexity. Assume that we have identified a structure that's irreducibly complex. There are three possible ways to deal with its origin.

  1. There is a plausible naturalistic explanation for the evolution of the irreducibly complex structure.
  2. There is currently no detailed naturalistic explanation that accounts for the evolution of the irreducibly complex structure.
  3. It is impossible for there to ever be a naturalistic explanation; therefore, god did it.

We know that there are good naturalistic explanations for the evolution of irreducibly complex structures. In fact, McLatchie mentions some of them that refuted his earlier claims. Behe has also backed off some of his claims in light of evidence that irreducibly complex structures can evolve without the help of god(s). This establishes that the mere existence of an irreducibly complex structure is not evidence for intelligent design.

Here's how Behe explains it on page 40 of Darwin's Black Box.

Even if a system is irreducibly complex (and thus cannot have been produced directly), however, one cannot definitively rule out the possibility of an indirect, circuitous route.

In some cases there is currently no good naturalistic explanation for the evolution of an irreducibly complex structure. This could be due to a real difficulty in coming up with a plausible scenario or it could be due to the fact that no scientist has bothered to do the investigation required because they don't care. In either case, the current lack of an explanation is not, in itself, evidence for an intelligent designer.

The third possibility is the one that counts. If you can prove that a naturalistic explanation is impossible then there must be a non-naturalistic explanation such as aliens, or god(s). McLatchie says the the sperm flagellum is irreducibly complex and that he cannot imagine how it could have evolved naturally. According to creationist logic, it follows that some alien, or some god, must have designed the original sperm flagellum.

McLatchie won't tell us when this happened or why the intelligent designer was so interested in sperm, but that's typical of Intelligent Design Creationsts—they require detailed explanations from scientists but not from their fellow creationists.