The proteome complexity myth

A reader pointed me to the ThermoFisher Scientific website. ThermoFisher Scientific is a major supply of scientific equipment and supplies. They created their life sciences wesite to help inform their customers and sell more products. The page I'm interested in is: Overview of Post-Translational Modifications (PTMs). It begins with,

Within the last few decades, scientists have discovered that the human proteome is vastly more complex than the human genome. While it is estimated that the human genome comprises between 20,000 and 25,000 genes (1), the total number of proteins in the human proteome is estimated at over 1 million (2). These estimations demonstrate that single genes encode multiple proteins. Genomic recombination, transcription initiation at alternative promoters, differential transcription termination, and alternative splicing of the transcript are mechanisms that generate different mRNA transcripts from a single gene (3).

The increase in complexity from the level of the genome to the proteome is further facilitated by protein post-translational modifications (PTMs). PTMs are chemical modifications that play a key role in functional proteomics, because they regulate activity, localization and interaction with other cellular molecules such as proteins, nucleic acids, lipids, and cofactors.

Revisiting Michael Behe's challenge and revealing a closed mind

It's been twenty years since Michael Behe published Darwin's Black Box and Intelligent Design Creationists are flagellating themselves over the fact that it had so little impact on creationism. The USA is becoming more secular with each passing year. Religion is on the decline.

In their attempt to deal with their defeat, the main ID blog has been publishing "Behe's Greatest Hits," which is a euphemistic way of saying "Behe's Greatest Failures." The latest one caught my eye. It's Best of Behe: An Open Letter to Professors Kenneth Miller and PZ Myers.

It takes you back more than two years to July 21, 2014. That's when Michael Behe issued his challenge to PZ Myers and Ken Miller. The challenge was based on his book The Edge of Evolution and specifically on the development of chloroquine resistance in Plasmodium falciparum. Behe starts with the assumption that cloroquine resistance is extremely rare—it occurs with a probability of roughly 10^-20. He concludes that resistance requires at least two different mutations that must occur simultaneously in an individual suffering from malaria while being treated with chloroquine.

The first assumption is approximately correct. Chloroquine resistance is rare. He was criticized for the second assumption; namely, that the overall probability of chloroquine resistance is just the probability of two mutations occurring simultaneously (e.g. 10^-10 × 10^-10 = 10^-20).

The best countries for atheists

The International Humanist and Ethical Union (IHEU) is a collection of Humanist, atheist, secular and similar organizations from many countries. It publishes the Freedom of Thought Report, which purports to be, "A global report on discrimination against humanists, atheists, and the nonreligious." The group intends to highlight systemic discrimination.

We believe it is important to document discriminatory national laws and state authorities which violate freedom of religion or belief and freedom of expression. As well as affecting the overtly nonreligious, such as atheists and Humanists, such systemic discrimination also often affects the religious, in particular minorities and non-conformists, and the unaffiliated (those who hold no particular religion or worldview-level belief).

Systemic, legal discrimination can include such things as established state churches (resulting in religious privilege), religious instruction provided without secular ethical alternative classes in schools, through to severe punishments such as prison for crimes of “insulting” religion, or death merely for expressing your atheism.

There are four categories of systemic discrimination: Constitution and government; Education and children’s rights; Family, community, society, religious courts and tribunals; and Freedom of expression advocacy of humanist values. For each category there are six possible rankings [see Ratings System]:

Black = Grave Violations
Red = Severe Discrimination
Orange = Systemic Discrimination
Yellow = Mostly Satisfactory
Green = Free and Equal
Gray = No Rating

Here's the result for the entire world.

Canada is ranked as "Systemic Discrimination" in all four categories. The USA gets the best rating (Free and Equal) in two categories: "Education and children’s rights" and "Freedom of expression advocacy of humanist values." It gets the second highest rating (Mostly Satisfactory) in: "Constitution and government" and "Family, community, society, religious courts and tribunals."

The conclusion is obvious. If you are an atheist you are much better off living in the USA than in Canada!

Hemant Mehta, better known as The Friendly Atheist, published the same figure on his blog a few days ago [New Report Highlights the Worst Countries in the World for Atheist Citizens. Many Canadians responded in the comments. One of them, CanuckAmuck, said,

I am dubious about some of the standards of this report. Not to appear butthurt, but to equate Canada to Russia in terms of "Constitution and the Government" is to say the least, asinine. And to report that "Society and Community" is "graver" for the atheist here than in the U.S. is likewise so.

I agree completely. Read the other comments to see what others think of this report.

Respond in the comments if you think atheists are better off in the USA than in Canada.

---

Using conservation to determine whether splice variants are functional

We've been having a discussion about function and how to recognize it. This is important when it comes to determining how much junk is in our genome [see Restarting the function wars (The Function Wars Part V)]. There doesn't seem to be any consensus on how to define "function" although there's general agreement on using sequence conservation as a first step. If some sequence under investigation is conserved in other species then that's a good sign that it's under negative selection and has a biological function. What if it's not conserved? Does that rule out function? The correct answer is "no" because one can always come up with explanations/excuses for such an observation. We discussed the example of de novo genes, which, by definition, are not conserved.

Let's look at another example: splice variants. Splice variants are different forms of RNA produced from the same gene. If they are biologically relevant then they will produce different forms of the protein (for protein-coding genes). This is an example of alternative splicing if, and only if, relevance has been proven.

Restarting the function wars (The Function Wars Part V)

The term "function wars" refers to debates over the meaning of the word "function" in biology. It refers specifically to the discussion about junk DNA because junk DNA is defined as DNA that does not have a biological function. The wars were (re-)started when the ENCODE Consortium decided to use a stupid definition of function in order to prove that most of our genome was functional. This prompted a number of papers attempting to create a more meaningful definition.

None of them succeeded, in my opinion, because biology is messy and doesn't lend itself to precise definitions. Look how difficult it is to define a "gene," for example. Or "evolution."

Nevertheless, some progress was made. Dan Graur has recently posted a summary of the two most important definitions of function [What does “function” mean in the context of evolution & what absurd situations may arise by using the wrong definition?]. The two definitions are "selected-effect" and "causal-role" (there are synonyms).

How many proteins in the human proteome?

Humans have about 25,000 genes. About 20,000 of these genes are protein-coding genes.¹ That means, of course, that humans make at least 20,000 proteins. Not all of them are different since the number of protein-coding genes includes many duplicated genes and gene families. We would like to know how many different proteins there are in the human proteome.

The latest issue of Science contains an insert with a chart of the human proteome produced by The Human Protein Atlas. Publication was timed to correspond with release of a new version of the Cell Atlas at the American Society of Cell Biology meeting in San Francisco. The Cell Atlas maps the location of about 12,000 proteins in various tissues and organs. Mapping is done primarily by looking at whether or not a gene is transcribed in a given tissue.

A total of 7367 genes (60%) are expressed in all tissues. These "housekeeping" genes correspond to the major metabolic pathways and the gene expression pathway (e.g. RNA polymerase subunits, ribosomal proteins, DNA replication proteins). Most of the remaining genes are tissue-specific or developmentally specific.

Suzan Mazur doesn't like Carl Zimmer

There weren't many science writers are the Royal Society meeting in London (UK) [New trends in evolutionary biology: biological, philosophical and social science perspectives]. Carl Zimmer was there and so was Suzan Mazur. Carl was there to learn and do some research. Suzan was there to promote herself as the main publicist of the paradigm shifters.

Carl Zimmer wrote a news article about the meeting for Quanta: Scientists Seek to Update Evolution. The subtitle was "Recent discoveries have led some researchers to argue that the modern evolutionary synthesis needs to be amended." It was a pretty fair article and pretty good reporting on what went on at the meeting. I would have been a bit more harsh about the success of the so-called "paradigm shifters" but Carl did a good job of conveying the skepticism exhibited by many at the meeting. [See Kevin Laland's new view of evolution for my take on these "revolutionaries."]

Kevin Laland's new view of evolution

The recent meeting at the Royal Society in London was organized by The Royal Society (UK) and The British Academy. The theme of the meeting was, "New trends in evolutionary biology: biological, philosophical and social science perspectives." The main organizers were Denis Noble, Nancy Cartwright, Patrick Bateson, John Dupré, and Kevin Laland. The point of the meeting was to discuss new evolutionary theory.

It's difficult to describe everything that went on at the meeting because so much of it was details about individual research results. These scientific talks were often presented as an alternative to modern ways of thinking about evolution. The general theme was that the Modern Synthesis was out-of-date and needed revision or, perhaps, replacement. There was very little discussion of evolutionary theory and how best to interpret those results. The data was supposed to speak for itself.

The only serious objections came from scientists who claimed the Modern Synthesis had already incorporated the ideas of niche construction, plasticity, epigenetics etc. This message was promoted mainly by Douglas Futuyma and Russell Lande. They weren't very successful.

Learning about modern evolutionary theory: the drift-barrier hypothesis

Many evolutionary biologists are engaged in research that focuses on large organisms that are (presumably) adapting to a local environment. These "field biologists" are mostly concerned with rapid evolutionary changes. Those kind of changes are almost always due to natural selection. Many of these biologists are not interested in molecular evolution and not interested in any process other than natural selection.

Unfortunately, this promotes an adaptationist mentality where all of evolution is viewed through the filter of natural selection. This is the view criticized by Stephen Jay Gould and Richard Lewontin back in 1978 when they presented the Spandrels paper at a Royal Society meeting in London (UK).

Gould, S. J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme. Proc. R. Soc. Lond. B 205:581-598. [doi: 10.1098/rspb.1979.0086

I believe there was a substantive change in our view of evolution back in the late 1960s and early 1970s. That's when the results of evolution at the molecular level were first being published. It lead to the development of Neutral Theory, Nearly-Neutral Theory and a growing appreciation of the importance of random genetic drift. Modern population genetics was able to cope easily with this new view of evolution.

On explaining science to the general public

Many science writers complain about the ability of scientists to explain their work to the general public. The latest example is from Susan Matheson, a science writer with a Masters degree in industrial engineering from Rutgers University (New Jersey, USA). She published the following article in Cell a leading journal in the field of cell biology, biochemistry, and molecular biology.

A Scientist and a Journalist Walk into a Bar…
by Susan Matheson, Cell 167: 1140–1143 (2016)[doi: 10.1016/j.cell.2016.10.051] [ScienceDirect PDF] [link from Susan Matheson]
Who are science journalists, and how can journalists and research scientists work together to improve science communication?

Mathesons begins with an anecdote about a science writer who won a Pulitzer Prize in 2011 for writing about a 4-year-old boy with a rare genetic disease. She concludes,

Edinburgh, Scotland

This is our first visit to Scotland. We rented an apartment in the top floor of this house in the middle of the city. It's a 20 minute walk to the port (Leith) and about the same distance to the old city (Edinburgh).

We'll be staying for two weeks in Scotland.

Our first meal in Scotland was at a pub in "the shore" near the main port.

---

Extending evolutionary theory? - Melinda Zeder

I will be attending the Royal Society Meeting on New trends in evolutionary biology: biological, philosophical and social science perspectives. I'll post each of the abstracts and ask for your help in deciding what question to pose to the speakers. Here's the abstract for Melinda Zeder's talk on Domestication: a model system for evolutionary biology.

In his book The Variation of Animals and Plants under Domestication Darwin used domestication as a model system to explore his theories about the role of natural selection in evolution. Gregor Mendel used peas to trace the rules of heredity that formed the basis of the science of genetics, and that, when combined with Darwinian evolution, formed the basis of the Modern Synthesis. It seems only appropriate for domestication to serve once again as a model system for assessing how recent insights into the role of multiple shaping processes and forms of inheritance can be incorporated into an extended understanding of evolution. This presentation explores the value of domestication in evaluating core assumptions that differentiate the classical Modern Synthesis and the Extended Evolutionary Synthesis including: 1. reciprocal causation, 2. developmental processes as drivers of evolutionary change, 3. inclusive inheritance, and 4. the tempo and rate of evolutionary change.

Melinda Zeder works at the National Museum of Natural History, Smithsonian Institution (USA). I think I'll ask her what domestication teaches us about the fixation of deleterious alleles by random genetic drift and how that fits into Darwin's ideas and her view of the Modern Synthesis.

---

Extending evolutionary theory? - Susan Antón

I will be attending the Royal Society Meeting on New trends in evolutionary biology: biological, philosophical and social science perspectives. I'll post each of the abstracts and ask for your help in deciding what question to pose to the speakers. Here's the abstract for Susan Antón's talk on Human evolution, niche construction and plasticity.

Recent humans are biocultural organisms. Our worldwide distribution and status as the lone surviving species of our genus signal a level of evolutionary success often explained by both biological and cultural mechanisms. A bio-behavioural package of traits that co-exist in Homo sapiens, including large brains and bodies, small teeth and jaws, extensive cooperative care, a great deal of developmental plasticity, and an extensive amount of niche construction, are variously implicated in our success or seen as its result.

It is broadly accepted that recent humans are ‘different’, particularly in the extent of our cultural interventions, than our earlier hominin forebears. But whether this is a difference in kind or degree, how far back that difference stretches, and whether those outcomes modifiable over an individual’s lifetime are important to human evolution is open to debate. Regardless of whether we accept exogenetic changes – including developmental niche construction – as consistent with an extension of, or break with the evolutionary synthesis, Homo erectus has often been proposed as the locus at which more ‘human like’ modes of behaviour (and presumably more biocultural evolution) is seated. But the paucity of the fossil record and the tenuously established links between bones and behaviours of interest limit our ability to test these assertions. I review the evolution of Homo and recent attempts to locate the transition to a biocultural organism with new data and by both working back from recent humans through archaeological time and working forward from ancestral genera.

Susan Antón is a professor of anthropology at New York University (New York, NY, USA).

It's interesting to learn about the history of life and the evolution of a particular species. However, that specific history usually doesn't usually have much impact on evolutionary theory. I wonder if some speakers are confused about the relationship between studying the history of life and the big picture of evolutionary theory? I fail to see how this study translates to a deeper understanding of the evolution of mushrooms, maple trees, and microbacteria.

---

Extending evolutionary theory? - Andrew Whiten

I will be attending the Royal Society Meeting on New trends in evolutionary biology: biological, philosophical and social science perspectives. I'll post each of the abstracts and ask for your help in deciding what question to pose to the speakers. Here's the abstract for Andrew Whiten's talk on A second inheritance system: the extension of biology through culture.

By the mid-twentieth century the behavioural sciences could offer only the sketchy beginnings of a scientific literature documenting evidence for cultural inheritance in animals – the transmission of traditional behaviours via imitation and other processes of learning from others (social learning). By contrast, recent decades have seen a massive growth in the documentation of such cultural phenomena, driven by long-term field studies and complementary laboratory experiments. Here I first offer an overview of the major discoveries in this field, which increasingly suggest that this ‘second inheritance system’, built on the shoulders of the primary genetic inheritance system, occurs widely amongst vertebrates and possibly in insects and other invertebrates too. Its novel characteristics suggest it should have major implications for our understanding of evolutionary biology. Two major questions arising are accordingly addressed. One concerns the extent to which this second system echoes or differs from the principal properties of the primary evolutionary system described in the neo-Darwinian synthesis of the twentieth century and its extensions under discussion at this meeting. A subsidiary issue here is how the answers may differ much according to whether the focus is on the massively cumulative cultural evolution distinctive of our own species, or on the forms of cultural transmission documented for other species. The second major, and related, question concerns the extent to which the new discoveries about animal cultural transmission extend evolutionary theory, either in addition to or through interaction with the primary, genetically based inheritance systems.

Andrew Whiten is an emeritus professor in the School of Psychology and Neuroscience at the University of St. Andrews (Scotland, UK). I'm curious to see his explanation of how cultural evolution in, say, bonobos, informs us about biological evolution.

Here's a possible question ...

The people living in St. Andrews experience a very different culture than the people living in the suburbs of Dallas, Texas. Both groups have been exposed to Donald Trump since he owns a golf club near St. Andrews but they are likely to react differently to Trump. How will these cultural differences affect the biological evolution of the two groups in Texas and Scotland?

---

Extending evolutionary theory? - Agustín Fuentes

I will be attending the Royal Society Meeting on New trends in evolutionary biology: biological, philosophical and social science perspectives. I'll post each of the abstracts and ask for your help in deciding what question to pose to the speakers. Here's the abstract for Agustín Fuentes' talk on
Human niche, human behaviour, human nature.

Scholars from a diverse range of disciplines disagree on what human nature is, what it could be, or even if there is one. There is no single ‘best’ discourse on, or mode of approach to, human nature. However, in the context of what we know about the evolutionary history, anthropology, and biology of Homo sapiens sapiens it is clear that an evolutionary approach should be among the principal modes of inquiry. At present we are faced with a few different narratives as to exactly what such an evolutionary approach entails. However, one point is clear: we need a robust and dynamic theoretical toolkit in order to develop a richer, and more nuanced, understanding of the cognitively sophisticated genus Homo and the diverse sorts of niches humans constructed and occupied across the Pleistocene, Holocene, and into the Anthropocene. In this talk I review current evolutionary approaches to ‘human nature’ and argue that we benefit from re-framing our investigations via the concept of the human niche and in the context of the Extended Evolutionary Synthesis (EES). In providing an overview of human evolution and the human niche I illustrate the benefits of moving the discourse on human nature(s) to an integrated evolutionary approach incorporating processes of the Extended Evolutionary Synthesis. This is not a replacement of earlier evolutionary approaches but rather an expansion and enhancement, a broadening of our toolkit and the landscape of inquiry. I offer brief examples from human evolutionary histories in support of these assertions.

Agustín Fuentes is a professor of anthropology at the University of Notre Dame in Indiana (USA). This is another talk about the nature of "human nature." Since I'll probably be skipping the previous talk I'll likely stay in some pub until this one is over. Looking forward to a "full English."

---