Thursday, May 10, 2018

Philosophers talking about genes

It's important to define what you mean when you use the word "gene." I use the molecular definition since most of what I write refers to DNA sequences. There's no perfect definition but, for most purposes, a good working definition is: A gene is a DNA sequence that is transcribed to produce a functional product. [What Is a Gene?].

There are two types of genes: protein-coding genes and those that specify a functional noncoding RNA (i.e ribosomal RNA, lincRNA). The gene is the part of the DNA that's transcribed so it includes introns. Transcription is controlled by regulatory sequences such as promoters, operators, and enhancers but these are not part of the gene.

In addition to genes, there are many other functional parts of the genome. In the case of eukaryotic genomes, these include centromeres, telomeres, origins of replication, SARs, and some other bits. None of this is new ... these functions have been known for decades and the working definition I use has been common among knowledgeable experts for half-a-century. Scientists know what they are talking about when they say that the human genome contains about 20,000 protein-coding genes and at least 5,000 genes for non-coding RNAs. They are comfortable with the idea that our genome has lots of other functional regions that lie outside of the genes.

Non-experts may not be familiar with the topic and they may have many misconceptions about genes and DNA sequences but we don't base our science on the views of non-experts.

Because of my interest in this topic, I was intrigued by the title of a new book, The Gene: from Genetics to Postgenomics. I ordered it a soon as I heard about it and I've just finished reading it. The version I read has been translated from German by Adam Bostanci.

The authors are Hans-Jörg Rheimberger of the Max Planck Institute for the History of Science in Berlin, Germany, and Staffan Müller-wille of the Centre for the study of the Life Sciences at the University of Exeter, UK. They are philosophers. They have two goals in mind: (1) to cover the history of the gene concept, and (2) to demonstrate that recent discoveries have radically undermined the concept of a gene.

... those ignorant of history are not condemned to repeat it; they are merely destined to be confused.

Stephen Jay Gould
Ontogeny and Phylogeny (1977)
They have only partially achieved the first goal. They recognize that the word "gene" can be used in many different contexts. In the first half of the twentieth century it referred almost exclusively to a unit of heredity or a unit of selection (or, more correctly, a unit of evolution). With the recognition that DNA was the genetic material, the word "gene" took on an additional meaning as a physical unit of function. In other words, acquired a physical form in contrast to the nebulous genetic meaning of the word. This is the molecular gene. It's at this point in their book that the authors lose their way. They never give us a molecular definition. I suspect they are thinking of a gene as coding sequences but you have to struggle to interpret their view of the molecular definition. They talk about "structural genes" and imply that the discovery of "regulatory genes" altered our concept of the gene but these terms were never used by experts in the way that the authors imagine (p. 66).

The authors never discuss the definition I prefer. It's not clear they have even considered it since they rely on the work of other philosophers who have also ignored it [see Debating philosophers: The molecular gene].

The problem with this part of the book (the part about the molecular gene) is that the authors seem to be confused about the difference between a molecular gene and the view that "genes" are the only thing that count in genetics, evolution, metabolism etc. They seem to think that the gene-centric view requires that everything be attributed to DNA sequences that encode proteins. Thus, when they recognize that important functional elements exist outside of genes, they conclude that the gene-centric view is fatally flawed. This leads us to their second goal where they try to convince us that the definition of "gene" is fatally flawed because genes aren't the only things that play an important role in genetics.

They fail in this goal because they are arguing against a strawman version of biology that no experts believe in.

This seems to be a common problem among philosophers. They refuse to use critical thinking to unravel the meaning of the molecular gene —a meaning that is really quite simple even though it's not perfect. Then they confuse themselves by thinking that knowledgeable experts use the word "gene" as a synonym for all functional sequences in the genome. Finally, they misunderstand the term "gene-centric" where the word "gene" is used metaphorically to refer to any DNA sequence that functions in population genetics and evolution. (Philosophers also tend to greatly over-estimate the influence of Richard Dawkins and the selfish gene.)

Theme
Genomes
& Junk DNA
The book contains all the usual misconceptions that come from reading the uniformed literature and assuming it represent the views of experts. Here's a short list of views that have been effectively challenged—and sometimes refuted— in the scientific literature ...
  1. Scientists were surprised that the human genome didn't contain 100,000 genes or more (p. 84)
  2. Crick's sequence hypothesis is no longer valid (p. 68)
  3. junk DNA is just a term used to describe DNA of no known function (p. 69)
  4. alternative splicing means that most genes can make many different proteins (pp. 70, 84, 107)
  5. evolutionary-developmental biology (evo-devo) threatens our understanding of the gene concept (pp. 88, 94-98)
  6. the ENCODE results have transformed our understanding of genes and genomes (p. 91)
  7. "the existence of epigenetic systems of inheritance poses the greatest challenge for the classical molecular gene concept" (p. 92)
  8. the discovery of Lamarckian inheritance casts doubt on the central dogma of molecular genetics (p. 92)
  9. plasticity is a problem (p. 98)
  10. 98% of the genome was thought to be junk but, thanks to ENCODE, we now know that it's full of regulatory elements (pp. 104-105)
In addition to this list of the usual misunderstandings and misconceptions, the authors have come up with two others that are quite novel. I'll quote directly from page 84 and let you see for yourselves ...
[There are] ... two further unexpected results of the genome project that complemented each other but also pointed in opposite directions. First, comparisons of the human genome with those of other primates revealed a surprisingly high degree of sequence conservation. Given remarkable differences in the physical constitution of these closest relatives of Homo sapiens, in particular differences in the so-called higher, mental faculties as a consequence of several million years of evolution, this degree of genomic affinity was astonishing. Major changes in the phenotype were apparently compatible with relatively minor changes in the genotype. The second surprising finding was that the genomes of different human individuals exhibit considerable differences. This genetic polymorphism was not, however, necessarily accompanied by correspondingly pronounced phenotypic differences.

Observations of this kind presented a serious challenge for gene-centrism and prompted proponents of the big genome projects to herald the dawn of an age of "postgenomics" in which the whole cell and the whole organism would move into the limelight.1
A little learning is a     dangerous thing;
drink deep, or taste not the     Pierian spring:
there shallow draughts     intoxicate the brain,
and drinking largely     sobers us again.
                  Alexander Pope
This book was published in 2017. It was revised and updated at that time. The scientific literature is full of debate and discussion about the topics covered here but you won't find any mention of controversy in this book. This can't be blamed exclusively on philosophers since there are many scientists who also ignore the controversies over junk DNA, alternative splicing, evolutionary theory, epigenetics etc. Like Rheinberger and Müller-Wille, they are content with promoting only one side of the story—the one that corresponds to their biases. Perhaps one should expect better critical thinking from philosophers?

There's one way in which this book differs from similar books written by scientists [see Human genome books]. Whereas scientists tend to quote scientific papers, Rheinberger and Müller-Wille rely heavily of the views of other philosophers. I get the distinct impression that almost all philosophers of science have reached the same conclusions and they support those (mostly false) conclusions by referencing each other instead of going back to the scientific literature [see When philosophers talk about genomes] [Debating philosophers: The Lu and Bourrat paper].

The views in this book are remarkably similar to those of Evelyn Fox Keller who is a Professor Emerita in the History and Philosophy of Science at the Massachusetts Institute of Technology in Boston, USA. I have already commented on one of her articles, "The Postgenomic Genome," in a previous post [When philosophers talk about genomes]. She is quoted several times in this book and her misconceptions are the same as those expressed by Rheinberger and Müller-Wille. You should follow the link to see what she says about genes and junk DNA in order to see for yourselves how badly modern philosphers have misinterpreted the science.


1. If you don't immediately see what's wrong with these arguments then ask a question in the comments.

8 comments :

  1. Do you like nature,Larry? How about gardening?

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  2. This isn't the first time I've seen the term "conservation" used in an annoying way, to mean slight difference without reference to a neutral expectation. It isn't the first time I've seen the sequence difference between humans and chimps called "surprising". Some creationists have even supposed that human and chimp started out with identical genomes, and all the morphological differences are non-genetic.

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    1. Lots of genes and proteins were sequenced in the 60s, 70s, 80s, and 90s. We learned that they were practically identical in closely related species like humans and chimps. The only “surprising” thing to come out of genome sequences was that the sequences of intervening regions were less identical. In fact they were drifting apart at the maximum rate indicating that they are junk.

      This is the exact opposite conclusion than the one arrived at by the authors of this book. As a general rule, philosophers of biology have failed to grasp the implications of modern population genetics and their views on evolution are 50 years out-of-date.

      This is true of most scientist as well but those scientists don’t claim to be experts in the history and philosophy of biology.

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  3. Its remarkable, but i welcome it, how much criticism thrown at Philosophers of science. I guess this means they might not be scientists but still they get paid for some reason. and so universal in error.!

    Plasticity is a interesting issue. It means bodyplans change without selection and this has been documented.

    The SURPRISING likeness of human/chimp genes etc DESPITE millions etc of years of segregation and with a intellectual difference fantastic IS very unlikely if evolutionism was true.
    many creationists point out that if we were cousins of primates, yet so much time/real differences, has passed tHEN our dna should be greatly different.
    its a good point and a cute point afainst evolutionists stressing how much our dna is like primates and SO we are related.
    Simply WE should be more genetically different if selection on mutations has been going on so long and to such effect.
    As a creationist I don't see intelligence/brain size as relevant to humans. We think with souls made in Gods image however we can use the argument against evolutionism.
    why are they so convince brain size equals smarts?? why is it not done within humans?? I heard whale brains were second biggest!

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    1. So if we think with our souls rather than our brains, do the results of "split brain" surgery mean we actually split our souls in two?

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  4. Given they get science so badly wrong might we infer a wider domain of error in their contributions?

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  5. A LITTLE LEARNING ...

    Fine quotations from Gould and Pope! The latter's quotation is at the beginning of my book on genes and non-genes (Evolutionary Bioinformatics, Springer 2016), where there is also much on Gould. I write with scientific and historical credentials, so may perhaps be excused for suggesting that even the third positions of codons are sometimes best considered, like introns, as non-genic.

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  6. Checking both authors CVs, I wonder what makes a philosopher? One of them did a German Diploma in paleontology, then after neobotanical work in a molecular biology project a PhD in philosophy. The other one has a masters degree in philosophy, but his PhD and his Habilitation were in molecular biology. Your blog post reads as if both came to biology from a complete outside perspective, but both have published papers as biologists at some point.

    Now, I haven't read their book and something might have got lost in translation, but they did contribute a Chapter to "A Companion to the Philosophy of Biology, 1" which I managed to find online. And of course I checked what I could on the original German edition and the English version cuts the subtitle "eine wisseschaftshistorische Bestandsaufnahme" - which makes it clear that they are not trying to define genes, they are trying to summarize how the term has been used historically. The chapter cites a study on how biologist currently define genes and a majority of respondents in 2008 replied that a gene is coding for a protein. If they goal is to describe how biologists are using the term, then they are not wrong to note this (your prefered version wasn't listed, but there was the option to write in a non-listed definition - but it went largely unused and not a single respondent gave the definition you use).
    Maybe the omission of the subtitle has given you wrong expectation - I fully expect a history of science to tell me about things that are wrong, science after all is a process of discarding wrong hypotheses. Maybe their earlier "A Cultural History of Heredity" would be more fun to read. The Amazon books preview includes a Francis Galton quote in which he compares politicians to ejaculate.

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