I'm trying to read all the recent books on the human genome and anything related. There are a lot of them. Here's a list with some brief comments. You should buy some of these books. There are others you should not buy under any circumstances.
The irony meter was a running joke on the newsgroup talk.origins back in the last century. Our irony meters were supposed to protect us from the craziness of creationists but as soon as we built a really good irony meter a new bit of creationist crazy came along and fried it. Apparently Jesus and Mo have the same problem.
You probably know that climate change is real and humans are a major cause of global warming. You probably know that life has evolved and the Biblical story of creation is false. Scientists have been actively promoting these ideas for decades and they've been relatively successful in most countries. What you may not know is that these are just two of the many controversial claims that scientists are fighting. You may even have been tricked into believing some of the other pseudoscientific claims that are out there.
Did you know that the dirt in your local park is full of bacteria? Each scoop of soil contains millions of bacteria. And it's not just in your local park, soil bacteria are everywhere. This is part of the reason why the total mass of bacteria on the planet outweighs all of the eukayotes combined, including elephants and whales.
There are hundreds of different species of bacteria in your local dirt. They are as different from each other as moose and mushrooms.Together, our results suggest that soil bacterial communities, like plant communities, are typically dominated by a relatively small subset of phylotypes.
Image Credit: Bacillus Sp. soil bacteria from The ecology of soil-borne human diseases
Delgado-Baquerizo, M., Oliverio, A.M., Brewer, T.E., Benavent-González, A., Eldridge, D.J., Bardgett, R.D., Maestre, F.T., Singh, B.K., and Fierer, N. (2018) A global atlas of the dominant bacteria found in soil. Science, 359(6373), 320-325. doi: doi: 10.1126/science.aap9516
Charles Darwin, the greatest scientist who ever lived, was born on this day in 1809 [Darwin still spurs tributes, debates] [Happy Darwin Day!] [Darwin Day 2017]. Darwin is mostly famous for two things: (1) he described and documented the evidence for evolution and common descent and (2) he provided a plausible scientific explanation of evolution—the theory of natural selection. He put all this in a book, The Origin of Species by Means of Natural Selection published in 1859—a book that spurred a revolution in our understanding of the natural world.
Modern evolutionary theory has advanced well beyond Darwin's theory but he still deserves to be honored for being the first to explain evolution and promote it in a way that convinced others. Here's one passage from the introduction to Origin of Species.
Although much remains obscure, and will long remain obscure, I can entertain no doubt, after the most deliberate and dispassionate study of which I am capable, that the view which most naturalists entertain, and which I formerly entertained—namely, that each species has been independently created—is erroneous. I am fully convinced that species are not immutable; but that those belonging to what are called the same genera are lineal descendants of some other and generally extinct species, in the same manner as the acknowledged varieties of any one species are the descendants of that species. Furthermore, I am convinced that Natural Selection has been the main but not exclusive means of modification.
Random genetic drift is the process whereby some allele frequencies change in a population by chance alone. The alleles are not being fixed or eliminated by natural selection. Most of the alleles affected by drift are neutral or nearly neutral with respect to selection. Some are deleterious, in which case they may be accidentally fixed in spite of being selected against. Modern evolutionary theory incorporates random genetic drift as part of population genetics and modern textbooks contain extensive discussions of drift and the influence of population size. The scientific literature has focused recently on the Drift-Barrier Hypothesis, which emphasizes random genetic drift [Learning about modern evolutionary theory: the drift-barrier hypothesis].
Most of the alleles that become fixed in a population are fixed by random genetic drift and not by natural selection. Thus, in a very real sense, drift is the dominant mechanism of evolution. This is especially true in species with large genomes full of junk DNA (like humans) since the majority of alleles occur in junk DNA where they are, by definition, neutral.1 All of the data documenting drift and confirming its importance was discovered by scientists. All of the hypotheses and theories of modern evolution were, and are, developed by scientists.Next to last, comes an attitude that seeks to deploy science to answer questions beyond its scope. It seems to me that it is exceedingly easy to come up with questions that either science is wholly unequipped to answer, or for which it can at best provide a (welcome!) degree of relevant background knowledge. I will leave it to colleagues in other disciplines to arrive at their own list, but as far as philosophy is concerned, the following list is just a start:Before getting to random genetic drift, I'll just note that my main problem with Pigliucci's argument is that there are other definitions of science that render his discussion meaningless. For example, I prefer the broad definition of science—the one that encompasses several of the Pigliucci's questions [Alan Sokal explains the scientific worldview][Territorial demarcation and the meaning of science]. The second point is that no matter how you define knowledge, philosophers haven't been very successful at adding to our knowledge base. They're good at questions (see above) but not so good at answers. Thus, it's reasonable to claim that science (broad definition) is the only proven method of acquiring knowledge. If that's scientism then I think it's a good working hypothesis.
[my emphasis LAM]
- In metaphysics: what is a cause?
- In logic: is modus ponens a type of valid inference?
- In epistemology: is knowledge “justified true belief”?
- In ethics: is abortion permissible once the fetus begins to feel pain?
- In aesthetics: is there a meaningful difference between Mill’s “low” and “high” pleasures?
- In philosophy of science: what role does genetic drift play in the logical structure of evolutionary theory?
- In philosophy of mathematics: what is the ontological status of mathematical objects, such as numbers?
The scientific literature on all the above is basically non-existent, while the philosophical one is huge. None of the above questions admits of answers arising from systematic observations or experiments. While empirical notions may be relevant to some of them (e.g., the one on abortion), it is philosophical arguments that provide the suitable approach.I hardly know what to say.
1. There are some very rare exceptions where a mutation in junk DNA may have detrimental effects.
I'm sad because we now have almost a whole generation of young people who know very little about Stephen Jay Gould. (He died of cancer in 2002.) I was thinking of this yesterday as I was preparing a post on bacteria. Gould's 1996 book, Full House, is about fundamental misconceptions of evolution and progress and it contains the following passage (p. 176) ...
We live now in the "Age of Bacteria." Our planet has always been in the "Age of Bacteria," ever since the first fossils—bacteria, of course—were entombed in rocks more than three and a half billion years ago.Listen to him make this point twenty years ago ...
On any possible, reasonable, or fair criterion, bacteria are—and always have been—the dominant forms of life on earth.
A recent letter in Nature draws attention to a serious (?) problem in modern society; namely, the persecution of junior scientists by older scientists who ask them tough questions. Anand Kumar Sharma warns us: "Don’t belittle junior researchers in meetings". Here's what he says, ...
The most interesting part of a scientific seminar, colloquium or conference for me is the question and answer session. However, I find it upsetting to witness the unnecessarily hard time that is increasingly given to junior presenters at such meetings. As inquisitive scientists, we do not have the right to undermine or denigrate the efforts of fellow researchers — even when their reply is unconvincing.
It is our responsibility to nurture upcoming researchers. Firing at a speaker from the front row is unlikely to enhance discussions. In my experience, it is more productive to offer positive queries and suggestions, and save negative feedback for more-private settings.
This is a post about alternative splicing. I've avoided using that term in the title because it's very misleading. Alternative splicing produces a number of different products (RNA or protein) from a single intron-containing gene. The phenomenon has been known for 35 years and there are quite a few very well-studied examples, including several where all of the splice regulatory factors have been characterized.
Sixty evolutionary biologists are going to meet next July in Salzburg (Austria)to discuss "a new paradigmatic understanding of genetic novelty" [Evolution – Genetic Novelty/Genomic Variations by RNA Networks and Viruses]. You probably didn't know that a new paradigm is necessary. That's because you didn't know that the old paradigm of random mutations can't explain genetic diversity. (Not!) Here's how the symposium organizers explain it on their website ...
There's solid evidence that 90% of your genome is junk. Most of it is transcribed at some time but the transcripts are transient and usually confined to the nucleus. They are junk RNA [Functional RNAs?]. This is the view held by many experts but you wouldn't know that from reading the scientific literature and the popular press. The opposition to junk DNA gets much more attention in both venues.
There are prominent voices expressing the view that most of the genome is devoted to producing functional RNAs required for regulating gene expression [John Mattick still claims that most lncRNAs are functional]. Most of these RNAs are long noncoding RNAs known as lncRNAs. Although most of them fail all reasonable criteria for function there are still those who maintain that tens of thousands of them are functional [How many lncRNAs are functional: can sequence comparisons tell us the answer?].I realize that most of you are tired of seeing criticisms of ENCODE but it's important to realize that most scientists fell hook-line-and-sinker for the ENCODE publicity campaign and they still don't know that most of the claims were ridiculous.
I was reminded of this when I re-read Brendan Maher's summary of the ENCODE results that were published in Nature on Sept. 6, 2012 (Maher, 2012). Maher's article appeared in the front section of the ENCODE issue.1 With respect to regulatory sequences he said ...The consortium has assigned some sort of function to roughly 80% of the genome, including more than 70,000 ‘promoter’ regions — the sites, just upstream of genes, where proteins bind to control gene expression — and nearly 400,000 ‘enhancer’ regions that regulate expression of distant genes ... But the job is far from done, says [Ewan] Birney, a computational biologist at the European Molecular Biology Laboratory’s European Bioinformatics Institute in Hinxton, UK, who coordinated the data analysis for ENCODE. He says that some of the mapping efforts are about halfway to completion, and that deeper characterization of everything the genome is doing is probably only 10% finished.
I'm working (slowly) on a book called What's in Your Genome?: 90% of your genome is junk! The first chapter is an introduction to genomes and DNA [What's in Your Genome? Chapter 1: Introducing Genomes ]. Chapter 2 is an overview of the human genome. It's a summary of known functional sequences and known junk DNA [What's in Your Genome? Chapter 2: The Big Picture]. Chapter 3 defines "genes" and describes protein-coding genes and alternative splicing [What's in Your Genome? Chapter 3: What Is a Gene?]. Chapter 4 is all about pervasive transcription and genes for functional noncoding RNAs [What's in Your Genome? Chapter 4: Pervasive Transcription].
Chapter 5 is Regulation and Control of Gene Expression.Chapter 5: Regulation and Control of Gene Expression
What do we know about regulatory sequences?
The fundamental principles of regulation were worked out in the 1960s and 1970s by studying bacteria and bacteriophage. The initiation of transcription is controlled by activators and repressors that bind to DNA near the 5′ end of a gene. These transcription factors recognize relatively short sequences of DNA (6-10 bp) and their interactions have been well-characterized. Transcriptional regulation in eukaryotes is more complicated for two reasons. First, there are usually more transcription factors and more binding sites per gene. Second, access to binding sites depends of the state of chromatin. Nucleosomes forming high order structures create a "closed" domain where DNA binding sites are not accessible. In "open" domains the DNA is more accessible and transcription factors can bind. The transition between open and closed domains is an important addition to regulating gene expression in eukaryotes.The limitations of genomics
By their very nature, genomics studies look at the big picture. Such studies can tell us a lot about how many transcription factors bind to DNA and how much of the genome is transcribed. They cannot tell you whether the data actually reflects function. For that, you have to take a more reductionist approach and dissect the roles of individual factors on individual genes. But working on single genes can be misleading ... you may miss the forest for the trees. Genomic studies have the opposite problem, they may see a forest where there are no trees.Regulation and evolution
Much of what we see in evolution, especially when it comes to phenotypic differences between species, is due to differences in the regulation of shared genes. The idea dates back to the 1930s and the mechanisms were worked out mostly in the 1980s. It's the reason why all complex animals should have roughly the same number of genes—a prediction that was confirmed by sequencing the human genome. This is the field known as evo-devo or evolutionary developmental biology.Box 5-1: Can complex evolution evolve by accident?
Open and closed chromatin domainsSlightly harmful mutations can become fixed in a small population. This may cause a gene to be transcribed less frequently. Subsequent mutations that restore transcription may involve the binding of an additional factor to enhance transcription initiation. The result is more complex regulation that wasn't directly selected.
Gene expression in eukaryotes is regulated, in part, by changing the structure of chromatin. Genes in domains where nucleosomes are densely packed into compact structures are essentially invisible. Genes in more open domains are easily transcribed. In some species, the shift between open and closed domains is associated with methylation of DNA and modifications of histones but it's not clear whether these associations cause the shift or are merely a consequence of the shift.Box 5-2: X-chromosome inactivation
Box 5-3: Regulating gene expression byIn females, one of the X-chromosomes is preferentially converted to a heterochromatic state where most of the genes are in closed domains. Consequently, many of the genes on the X chromosome are only expressed from one copy as is the case in males. The partial inactivation of an X-chromosome is mediated by a small regulatory RNA molecule and this inactivated state is passed on to all subsequent descendants of the original cell.
rearranging the genome
ENCODE does it againIn several cases, the regulation of gene expression is controlled by rearranging the genome to bring a gene under the control of a new promoter region. Such rearrangements also explain some developmental anomalies such as growth of legs on the head fruit flies instead of antennae. They also account for many cancers.
Genomic studies carried out by the ENCODE Consortium reported that a large percentage of the human genome is devoted to regulation. What the studies actually showed is that there are a large number of binding sites for transcription factors. ENCODE did not present good evidence that these sites were functional.Does regulation explain junk?
The presence of huge numbers of spurious DNA binding sites is perfectly consistent with the view that 90% of our genome is junk. The idea that a large percentage of our genome is devoted to transcriptional regulation is inconsistent with everything we know from the the studies of individual genes.Box 5-3: A thought experiment
Small RNAs—a revolutionary discovery?Ford Doolittle asks us to imagine the following thought experiment. Take the fugu genome, which is very much smaller than the human genome, and the lungfish genome, which is very much larger, and subject them to the same ENCODE analysis that was performed on the human genome. All three genomes have approximately the same number of genes and most of those genes are homologous. Will the number of transcription factor biding sites be similar in all three species or will the number correlate with the size of the genomes and the amount of junk DNA?
Does the human genome contain hundreds of thousands of gene for small non-coding RNAs that are required for the complex regulation of the protein-coding genes?A “theory” that just won’t die
"... we have refuted the specific claims that most of the observed transcription across the human genome is random and put forward the case over many years that the appearance of a vast layer of RNA-based epigenetic regulation was a necessary prerequisite to the emergence of developmentally and cognitively advanced organisms." (Mattick and Dinger, 2013)What the heck is epigenetics?
Epigenetics is a confusing term. It refers loosely to the regulation of gene expression by factors other than differences in the DNA. It's generally assumed to cover things like methylation of DNA and modification of histones. Both of these effects can be passed on from one cell to the next following mitosis. That fact has been known for decades. It is not controversial. The controversy is about whether the heritability of epigenetic features plays a significant role in evolution.Box 5-5: The Weismann barrier
How should science journalists cover this story?The Weisman barrier refers to the separation between somatic cells and the germ line in complex multicellular organisms. The "barrier" is the idea that changes (e.g. methylation, histone modification) that occur in somatic cells can be passed on to other somatic cells but in order to affect evolution those changes have to be transferred to the germ line. That's unlikely. It means that Lamarckian evolution is highly improbable in such species.
The question is whether a large part of the human genome is devoted to regulation thus accounting for an unexpectedly large genome. It's an explanation that attempts to refute the evidence for junk DNA. The issue is complex and very few science journalists are sufficiently informed enough to do it justice. They should, however, be making more of an effort to inform themselves about the controversial nature of the claims made by some scientists and they should be telling their readers that the issue has not yet been resolved.
One of the most interesting topics in my molecular evolution class was the discussion over the importance of sex. Most students seem to think the problem is solved. They were taught that sex increases variation in a population and this gives sexual populations an evolutionary advantage. The fact that sex (recombination) breaks up as many linkages as it creates makes the explanation much less viable. The fact that there's very little evidence to support the claim comes as quite a surprise to my students. Sex is still one of the greatest mysterious in evolutionary biology [What did Joe Felsenstein say about sex?] [Everything you thought you knew about sex is probably wrong].
Kevin Laland has just published another critique of modern evolutionary theory. This one appears in Aeon [Evolution unleashed]. His criticism is based on a naive and outdated view of modern evolutionary biology. That view has been widely criticized in the past but Laland continues to ignore such criticisms [e.g. Kevin Laland's new view of evolution].
Here's how he describes the state of modern evolutionary biology.If you are not a biologist, you’d be forgiven for being confused about the state of evolutionary science. Modern evolutionary biology dates back to a synthesis that emerged around the 1940s-60s, which married Charles Darwin’s mechanism of natural selection with Gregor Mendel’s discoveries of how genes are inherited. The traditional, and still dominant, view is that adaptations – from the human brain to the peacock’s tail – are fully and satisfactorily explained by natural selection (and subsequent inheritance). Yet as novel ideas flood in from genomics, epigenetics and developmental biology, most evolutionists agree that their field is in flux. Much of the data implies that evolution is more complex than we once assumed.
