Santi Garcia-Vallvé reviews my book

Santi Garcia-Vallvé has reviewed my book in the journal Mètode. It's written in Catalan but Santi was kind enough to send me a translation.

OUR GENOME HAS NOT YET SPOKEN ITS LAST WORD

What's in Your Genome? 90% of Your Genome Is Junk. Laurence A. Moran. Aevo University of Toronto Press (UTP). May 2023. 392 pages.

What's in Your Genome? exposes a variety of topics and concepts in molecular biology, genetics, and evolution that have been misunderstood by scientists and the general public. Many of these concepts are widely accepted, despite ongoing debate about them. Although the author, Larry Moran, has exhaustively discussed most of these issues on his blog "Sandwalk: Strolling with a sceptical biochemist", discussing them in a book allows for a more in-depth investigation.

One of these recurring themes is Francis Crick 's 1957 proposal of the Central Dogma of Molecular Biology. In his book Molecular Biology of the gene, James Watson adapted this concept by summarizing in a figure the flow of genetic information from DNA to RNA and then to proteins. This version was widely adopted, and many scientists now assume that it was the original definition. However, Crick claimed that once the information had been transferred to the proteins, it could not be returned to nucleic acids. Other controversial topics discussed in the book include the number of genes encoded in the human genome, the concept of Junk DNA and the prevalence of alternative splicing in the transcription of the human genome. Larry takes a certain viewpoint on all these problems, as evidenced by the title of the book, but he also presents arguments from all sides. Throughout the book, he argues that scientists must present evidence in support of and against their findings, as well as contextualise their discoveries in light of the knowledge of the subject. Thus, the first chapters of the book describe in depth the basic ideas of genetics, genetics and evolution that are required to understand the arguments that he will present later, showing also when and how they were discovered.

This is a highly recommendable book that pushed us to think about how research findings are explained and the importance of placing them in their proper context. The media frequently looks for stunning headlines and there is growing demand to assess the social impact of a project, article or scientific project. However, if we exaggerate our findings, we risk exacerbating further diminishing the general lack of interest in scientific news. Everyone is responsible that this does not happen.

Santi Garcia-Vallvé is an associate professor in the Department of Biochemistry and Biotechnology at Rovira i Virgili University (URV) in Tarragona, Spain, and a member of the Chemoinformatics and Nutrition research group."

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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."

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John Farrell reviews my book: "Junk DNA: Why human beings have inherited a 'sloppy genome.'"

Here's an excerpt from his review.

In his new book "What’s in Your Genome?", Laurence A. Moran shows that all the research done in the decades since that letter was written has confirmed what Crick, Jukes, and other specialists believed all along: much of our DNA is indeed a kind of “junk.”

Junk DNA: Why human beings have inherited a sloppy genome

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What's in Your Genome?: 90% of Your Genome Is Junk

If you are interested in learning more about junk DNA here's some links to relevant information.

Prologue
Chapter 1: Introducing Genomes
Chapter 2: The Evolution of Sloppy Genomes
Chapter 3: Repetitive DNA and Mobile Genetic Elements
Chapter 4: Why Don't Mutations Kill Us?
Chapter 5: The Big Picture
Chapter 6: How Many Genes? How Many Proteins?
Chaper 7: Gene Families and the Birth and Death of Genes
Chapter 8: NoncodingGenes and Junk RNA
Chapter 9: The ENCODE Publicity Campaign
Chapter 10: Turning Genes On and Off
Chapter 11: Zen and the Art of Coping with a Sloppy Genome

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Gert Korthof reviews my book

Gert Korthof thinks that the current view of evolution is incomplete and he's looking for a better explanation. He just finished reading my book so he wrote a review on his blog.

Scientists say: 90% of your genome is junk. Have a nice day! Biochemist Laurence Moran defends junk DNA theory

The good news is that I've succeeded in making Gert Korthof think more seriously about junk DNA and random genetic drift. The bad news is that I seem to have given him the impression that natural selection is not an important part of evolution. Furthermore, he insists that "evolution needs both mutation and natural selection" because he doesn't like the idea that random genetic drift may be the most common mechanism of evolution. He thinks that statement only applies at the molecular level. But "evolution" doesn't just refer to adaptation at the level of organisms. It's just not true that all examples of evolution must involve natural selection.

I think I've failed to explain the null hypothesis correctly because Korthof writes,

It's clear this is a polemical book. It is a very forceful criticism of ENCODE and everyone who uncritically accepts and spreads their views including Nature and Science. I agree that this criticism is necessary. However, there is a downside. Moran writes that the ENCODE research goals of documenting all transcripts in the human genome was a waste of money. Only a relatively small group of transcripts have a proven biological function ("only 1000 lncRNAs out of 60,000 were conserved in mammals"; "the number with a proven function is less than 500 in humans"; "The correct null hypothesis is that these long noncoding RNAs are examples of noisy transcription", or junk RNA"). Furthermore, Moran also thinks it is a waste of time and money to identify the functions of the thousands of transcripts that have been found because he knows its all junk. I disagree. The null hypothesis is an hypothesis, not a fact. One cannot assume it is true. That would be the 'null dogma'.

That's a pretty serious misunderstanding of what I meant to say. I think it was a worthwhile effort to document the number of transcripts in various cell types and all the potential regulatory sequences. What I objected to was the assumption by ENCODE researchers that these transcripts and sites were functional simply because they exist. The null hypothesis is no function and scientists must provide evidence of function in order to refute the null hypothesis.

I think it would be a very good idea to stop further genomic surveys and start identifying which transcripts and putative regulatory elements are actually functional. I'd love to know the answer to that very important question. However, I recognize that it will be expensive and time consuming to investigate every transcript and every putative regulatory element. I don't think any lab is going to assign random transcripts and random transcription factor binding sites to graduate students and postdocs because I suspect that most of those sequences aren't going to have a function. If I were giving out grant money I give it to some other lab. In that sense, I believe that it would be a waste of time and money to search for the function of tens of thousands of transcripts and over one million transcription factor binding sites.

That not dogmatic. It's common sense. Most of those transcripts and binding sites are not conserved and not under purifying election. That's pretty good evidence that they aren't functional, especially if you believe in the importance of natural selection.

There's lot more to his review including some interesting appendices. I recommend that you read it carefully to see a different perspective than the one I adocate in my book.

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Chapter 11: Zen and the Art of Coping with a Sloppy Genome

In last chapter of my book I try to convince readers that biochemistry, molecular biology, and evolution are sloppy processes and the idea of a sloppy genome is a logical consequence of evolution. The chapter contains Chautauguas on genomics, the function wars, intelligent design creationists, and scientific controversies.

Click on this link to see more.
Chapter 11: Zen and the Art of Coping with a Sloppy Genome

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Chapter 10: Turning Genes On and Off

Francis Collins, and many others, believe that the concept of junk DNA is outmoded because recent discoveries have shown that most of the human genome is devoted to regulation. This is part of a clash of worldviews where one side sees the genome as analogous to a finely tuned Swiss watch with no room for junk and the other sees the genome as a sloppy entity that's just good enough to survive.

The ENCODE researchers and their allies claim that the human genome contains more than 600,000 regulatory sites and that means an average of 24 per gene covering about 10,000 bp per gene. I explain why these numbers are unreasonable and why most of the sites they identify have nothing to do with biologically significant regulation.

This chapter also covers the epigenetics hype and restriction/modification.

Click on this link to see more.
Chapter 10: Turning Genes On and Off

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Chapter 9: The ENCODE Publicity Campaign

In September 2012, the ENCODE researchers published a bunch of papers claiming to show that 80% of the human genome was functional. They helped orchestrate a massive publicity campaign with the help pf Nature— a campaign that succeeded in spreading the message that junk DNA had been refuted.

That claim was challenged within 24 hours by numerous scientists on social media. They pointed out that the ENCODE researchers were using a ridiculous definition of function and that they had completely ignored all the evidence for junk DNA. Over the next two years there were numerous scientific papers criticizing the ENCODE claims and the ENCODE researchers were forced to retract the claim that they had proven that 80% of the genome is functional.

I discuss what went wrong and lay the blame mostly on the ENCODE researchers who did not behave as proper scientists when presenting a controversial hypothesis. The editors of Nature share the blame for not doing a proper job of vetting the ENCODE claims and not subjecting the papers to rigorous peer review. Science writers also failed to think critically about the results they were reporting.

Click on this link to see more.
Chapter 9: The ENCODE Publicity Campaign

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Chapter 8: Noncoding Genes and Junk RNA

I think there are no more than 5,000 noncoding genes but many scientists claim that there are tens of thousands of newly discovered noncoding genes. I describe the known noncoding genes (less than 1000) and explain why many of the transcripts detected are just junk RNA produced by spurious transcription. The presence of abundant noncoding genes will not solve the Deflated Ego Problem.

This chapter covers the misconceptions about the Central Dogma and how they are incorrectly used to try and discredit junk DNA. The views of John Mattick are explained and refuted. I end the chapter with a plea to adopt a worldview that can accommodate messy biochemistry and a sloppy genome that's full of junk DNA.

Click on this link to see more.

Chapter 8: NoncodingGenes and Junk RNA

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Chapter 7: Gene Families and the Birth & Death of Genes

This chapter describes gene families in the human genome. I explain how new genes are born by gene duplication and how they die by deletion or by becoming pseudogenes. Our genome is littered with pseudogenes: how do they evolve and are they all junk? What are the consequences of whole genome duplications and what does it teach us about junk DNA? How many real ORFan genes are there and why do some people think there are more? Finally, you will learn why dachshunds have short legs and what "The Bridge on the River Kwai" has to do with the accuracy of the human genome sequence.

Click on this link to see more.

Gene Families and the Birth and Death of Genes

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Chapter 6: How Many Genes? How Many Proteins?

Here's a link to the summary of what's in Chapter 6. The important topics are the correct definition of "gene" and the number of protein-coding genes. I explain the false history concerning the number of genes that were predicted when the human genome sequence was published. This is the chapter that introduces the Deflated Ego Problem.

The last half of the chapter covers introns and why most intron sequences are junk. There's an extensive discussion of alternative splicing and why most genes are NOT alternatively spliced in spite of what you might have been taught.

Chapter 6: How Many Genes? How Many Proteins?

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"You like me!"

The endorsements for my book are in.

One of the last steps in publishing a book is to collect endorsements—favorable statements from famous people who urge you to buy the book. These short endorsements will appear in the front of the book and on the book jacket (dust jacket). They may also appear on various websites in order to promote sales.

The trick is to sent the book out for review to as many people as possible and hope that one or two will like it well enough to say something nice. I'm pleased to report that there were, indeed, a few people who liked the book well enough to endorse it.

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The title of this post is from Sally Field's acceptance speech on winning the Academy Award for best actress in 1985. She said, "I can't deny the fact that you like me. Right now, you like me!"

I finished my book!

The last few weeks have been hectic. I got the first page proofs about a month ago and my job was to proof read those pages and prepare the index. Proof reading is tedious and the pressure is on because after that you can only make minor changes. I found several serious errors that I had made so that was a bit deflating. In one of them, I completely screwed up the calculations of the size of a typical protein-coding gene and the amount of the genome that was devoted to genes.

The index was hard because I wanted to have as comprehensive an index as possible. Publishers usually give you the option of hiring someone to do the index and taking the charges out of your royalty. If you look at some of the books on your shelf you can easily pick out the ones that were indexed by someone who doesn't understand the material.

The next step is "second pages" or the almost final version of the book. I had to proof read that version knowing that this was the last chance to fix anything. This includes the index, which I was seeing for the first time in a formatted version after the copy editor had dealt with it. I found 55 issues in this version that had to be fixed. This included several copy edit changes that I had missed on two previous passes (e.g. "cyIne" instead of "cytosine.") That's very scary—I wonder how many others we've missed?¹

That's it for me! The book is now "locked" for me. The publisher will deal with the issues I found, and a few others, and then send it off to the printer at the end of next week. It's still scheduled for release on May 16th. You can't see much about my book on the US version of Amazon but there's more on the Canadian version [What's in Your Genome].

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1. There have always been some errors in my textbooks but all the copy editors had degrees in biochemistry so there were lots of people who could catch mistakes. Publishing a trade book is an entirely different kettle of fish because none of the people who worked on the book knew anything about the subject and most had no science background whatsoever.

Read a short preview of What's in Your Genome

Check out this website, What's in Your Genome if you want to see a preview of my book (Preface, Prologue, part of Chapter 1).

The book will be released on May 16, 2023. We are currently working on the proofs prior to typesetting. You can preorder the hardcover version on Amazon.ca (Canada) for $39.95 (Cdn). I don't know when the electronic version will be available. You can also preorder on Amazon.co.uk for £26.99.

You can't yet preorder on Amazon.com and there's no information on that site about availability. I don't know about other Amazon sites.

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