Junk in Your Genome: Pseudogenes

 
Pseudogenes are non-functional DNA sequences that resemble genes. Much of the DNA related to transposable elements falls into this category. There are ribosomal RNA and tRNA pseudogenes but the term usually refers to sequences that resemble protein-encoding genes.

THEME

Genomes & Junk DNA

Total Junk so far

    46%
There are two kinds of pseudogenes derived from protein-encoding genes. Those derived from reverse transcription of mRNA and the re-integration of double-stranded DNA into the genome are called "processed" pseudogenes because the mRNA precursor was processed to give mature mRNA before being copied. Consequently, processed pseudogenes do not have introns. They also don't have promoters so they cannot be transcribed.

The other kind of pseudogene arises following a gene duplication event. One of the copies acquires a mutation that inactivates it. This is usually not harmful because the other copy remains intact. It is the fate of most duplicated genes to become a pseudogene by inactivation.

The original meaning of "junk" DNA referred to pseudogenes (reviewed in Gregory 2005) but the term is now used frequently to mean any non-functional DNA. That's the definition I use here.

Ensembl lists 2,081 pseudogenes in the human genome but that's very low compared to other studies [Human Genome]. The number of processed pseudogenes range from several thousand up to 17 thousand (Drouin 2006). The ENCODE project found 118 pseudogenes in their detailed analysis of 1% of the genome (Solovyev et al. 2006). This suggest that there are 11,800 pseudogenes in the entire genome.

A number of studies suggest that the number of processed pseudogenes is approximately the same as the number of inactivated duplicated genes (reviewed in Taylor and Raes 2005). In the case of processed pseudogenes, there are many copies of a relatively small subset of the total number of genes. In other words, lots of genes do not spawn pseudogenes and those that do have many offspring. This is because there is a bias in favor of genes that are highly expressed n the germ line.

The total number of pseudogenes in the genome is likely to be close to the number of genes based on extrapolations from detailed analyses of small segments of the genome or single chromosomes.

If we assume that there are 10,000 processed pseudogenes averaging 2 kb each then this represents 20 Mb or 0.06% of the genome. If there are an equal number of other pseudogenes then this is 10,000 × 60 kb = 600 Mb or 18% of the genome. This is all junk DNA but it overlaps extensively with the junk DNA from transposable elements. It is further evidence that substantial parts of the genome are non- functional but since most of that sequence would be introns in an active gene, it would count as junk DNA even if the gene were active. It's best to just count the inactive exons in order to avoid double counting.

Thus, pseudogenes are about 1.2% of the genome and all of it is junk.^1,2

---

1. A small number of former pseudogenes have been reactivated. They are no longer pseudogenes so they don't count as junk. A small number of pseudogenes have acquired a separate function so they don't count as junk. There do not appear to be very many examples.

2. There are many scientists who have tried to make the case for pseudogenes having some sort of function. The most common speculation is that they serve as an important reservoir of sequence information that can be accessed by recombination and/or re-activation (e.g., Balakirev and Ayala 2003).

Balakirev, E.S. and Ayala, F.J. (2003) PSEUDOGENES: Are They “Junk” or Functional DNA? Ann. Rev. Genet. 37:123-151. [doi:10.1146/annurev.genet.37.040103.103949]

Drouin, G. (2006)Processed pseudogenes are more abundant in human and mouse X chromosomes than in autosomes. Mol. Biol. Evol. 23:1652-1655 [PubMed]

Gregory, T.R. (2005) "Genome Size Evolution in Animals" in The Evolution of the Genome. Elsevier Academic Press, New York (USA).

Solovyev, V., Kosarev, P., Seledsov, I. and Vorobyev, D. (2006) Automatic annotation of eukaryotic genes, pseudogenes and promoters. Genome Biol. 7 Suppl 1:S10.1-12 [ PubMed

Taylor, J.S. and Raes, J. (2005) "Small-Scale Gene Duplications" in The Evolution of the Genome. Elsevier Academic Press, New York (USA).

Junk in Your Genome: SINES

In a previous posting I talked about Long Interspersed Elements or LINEs [Junk in Your Genome: LINEs]. These are retrotransposons that make up a significant percentage of the junk DNA in your genome. Most of them are completely defective, they are incapable of transposing and they usually don't encode any functional proteins.

THEME

Genomes & Junk DNA
A minority of LINEs are still active. Their genes for reverse transcriptase and endonuclease are still functional and the the transposons still retain the end sequences necessary for insertion.

Today I want to discuss Short Interspersed Elements or SINEs. These pieces of DNA tend to be only 100-400 bp in length but they contain all the features of transposons at their ends. The most important of these features is a short repeat of genomic DNA.

Most SINEs are related to the genes for small RNAs and, more specifically, to genes that are transcribed by RNA polymerase III [Transcription of the 7SL Gene]. Recall that one of the characteristics of Class III genes is that many of them have internal promoters. What this means is that the start site for transcription lies entirely within the DNA that's transcribed.

SINEs look like this:

The blue line represents the transcribed region of the SINE and the black line is the genomic DNA flanking the insert. At each end there is a short (about 5 bp) direct repeat representing the remnants of the insertion event. The 3′ end of the SINE has a short stretch of adenlyate residues (poly A) that is required for mobility.

A typical SINE is only about 100-400 bp long. As mentioned above, one of the key features of SINEs is the presence of an internal promoter to which RNA polymerase III binds. Class III promoters generally have two separate binding regions designated Box A and Box B. All SINEs are derived from genes encoding cellular RNAs such as tRNA, 7SL RNA, U RNAs, etc. These genes are transcribed by RNA polymerase III.

The SINE is transcribed because of the presence of the internal promoter. The transcript may be copied by reverse transcriptase produced from active LINEs in the genome. The DNA:RNA hybrid can be converted to double-stranded DNA and integrated into the genome as a transposable element using the LINE endonuclease. The process is similar to the mechanism that produces processed pseudogenes derived from mRNA but the difference is that the SINEs can still be transcribed when they have integrated into the genome whereas the mRNA pseudogenes have been separated from their promoter.

In the mouse genome there are two large families of SINEs. The B1 family is derived from a truncated and rearranged 7SL RNA. (Recall that 7SL RNA is the RNA component of signal recognition particle.) The B2 family comes from a tRNA that has acquired a terminal extension (Dewannieux and Heidmann 2005).

Each mouse family has about one million copies and together they make up about 20% of the mouse genome. Most of these transposable elements are defective because they have acquired mutations. They are not mobile and many are not transcribed.

In humans, the largest family of SINEs is called Alu elements after the fact that the sequence is cleaved by the restriction endonuclease Alu. These SINEs are also derived from 7SL RNA but the rearrangement is different from that in mouse. (They have a common ancestor.) There are about one million Alu elements in the human genome.

SINEs make up about 13% of the human genome. The largest proportion, by far, is Alu elements but there are small numbers of SINEs derived from other cellular RNAs such as the U RNAs required for splicing and snoRNAs (Garcia-Perez et al. 2007).

SINEs are parasites (selfish DNA). They are not essential for human survival and reproduction, especially the huge majority of SINEs that are defective. Thus, at least 13% of the human genome is clearly junk. The total amount of junk DNA contributed by all transposable elements is 44% of the genome (Kidwell 2005).

---

Dewannieux, M. and Heidmann, T. (2005) L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells. J. Mol. Biol. 349:241-7 [PubMed]

Garcia-Perez, J.L., Doucet, A.J., Bucheton, A., Moran, J.V. and Gilbert, N. (2007) Distinct mechanisms for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase. Genome Res. 17:602-11. [PubMed] [Genome Research]

Kidwell, M. (2005) "Transposable Elements" in The Evolution of the Genome T.R. Gregory ed. Elsevier Academic Press, New York (USA)

Regulation of Transcription

 
From Horton et al. (2006), pp. 663-665.

---

Many genes are expressed in every cell. The expression of these housekeeping genes is said to be constitutive. In general, such genes have strong promoters and are transcribed efficiently and continuously. Genes whose products are required at low levels usually have weak promoters and are transcribed infrequently. In addition to constitutively expressed genes, cells contain genes that are expressed at high levels in some circumstances and not at all in others. Such genes are said to be regulated.

Regulation of gene expression can occur at any point in the flow of biological information but occurs most often at the level of transcription. Various mechanisms have evolved that allow cells to program gene expression during differentiation and development and to respond to environmental stimuli.

The initiation of transcription of regulated genes is controlled by regulatory proteins that bind to specific DNA sequences. Transcriptional regulation can be negative or positive. Transcription of a negatively regulated gene is prevented by a regulatory protein called a repressor. A negatively regulated gene can be transcribed only in the absence of active repressor. Transcription of a positively regulated gene can be activated by a regulatory protein called an activator. A positively regulated gene is transcribed poorly or not at all in the absence of the activator.


Repressors and activators are often allosteric proteins whose function is modified by ligand binding. In general, a ligand alters the conformation of the protein and affects its ability to bind to specific DNA sequences. For example, some repressors control the synthesis of enzymes for a catabolic pathway. In the absence of substrate for these enzymes, the genes are repressed. When substrate is present, it binds to the repressor, causing the repressor to dissociate from the DNA and allowing the genes to be transcribed. Ligands that bind to and inactivate repressors are called inducers because they induce transcription of the genes controlled by the repressors. In contrast, some repressors that control the synthesis of enzymes for a biosynthetic pathway bind to DNA only when associated with a ligand. The ligand is often the end product of the biosynthetic pathway. This regulatory mechanism ensures that the genes are turned off as product accumulates. Ligands that bind to and activate repressors are called corepressors. The DNA-binding activity of allosteric activators can also be affected in two ways by ligand binding. Four general strategies for regulating transcription are illustrated in the figures. Examples of all four strategies have been identified.


Few regulatory systems are as simple as those described above. For example, the transcription of many genes is regulated by a combination of repressors and activators or by multiple activators. Elaborate mechanisms for regulating transcription have evolved to meet the specific requirements of individual organisms. When transcription is regulated by a host of mechanisms acting together, a greater range of cellular responses is possible. By examining how the transcription of a few particular genes is controlled, we can begin to understand how positive and negative mechanisms can be combined to produce the remarkably sensitive regulation seen in bacterial cells.

©Laurence A. Moran and Pearson Prentice Hall

---

Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Preintic Hall, Upper Saddle River N.J. (USA)

Theme: Genomes & Junk DNA

Junk in Your Genome

Transposable Elements: (44% junk)

      DNA transposons:
         active (functional): <0.1%
         defective (nonfunctional): 3%
      retrotransposons:
         active (functional): <0.1%
         defective transposons
            (full-length, nonfunctional): 8%
            L1 LINES (fragments, nonfunctional): 16%
            other LINES: 4%
            SINES (small pseudogene fragments): 13%
            co-opted transposons/fragments: <0.1% ^a

^aCo-opted transposons and transposon fragments are those that have secondarily acquired a new function.

Viruses (9% junk)

      DNA viruses
         active (functional): <0.1%
         defective DNA viruses: ~1%
      RNA viruses
         active (functional): <0.1%
         defective (nonfunctional): 8%
         co-opted RNA viruses: <0.1% ^b

^bCo-opted RNA viruses are defective integrated virus genomes that have secondarily acquired a new function.

Pseudogenes (1.2% junk)
      (from protein-encoding genes): 1.2% junk
      co-opted pseudogenes: <0.1% ^c

^cCo-opted pseudogenes are formerly defective pseudogenes those that have secondarily acquired a new function.

Ribosomal RNA genes:
      essential 0.22%
      junk 0.19%

Other RNA encoding genes
      tRNA genes: <0.1% (essential)
      known small RNA genes: <0.1% (essential)
      putative regulatory RNAs: ~2% (essential) Protein-encoding genes: (9.6% junk)
      transcribed region:  
            essential 1.8%  
            intron junk (not included above) 9.6% ^d

^dIntrons sequences account for about 30% of the genome. Most of these sequences qualify as junk but they are littered with defective transposable elements that are already included in the calculation of junk DNA.

Regulatory sequences:
      essential 0.6%

Origins of DNA replication
      <0.1% (essential) Scaffold attachment regions (SARS)
      <0.1% (essential) Highly Repetitive DNA (1% junk)
      α-satellite DNA (centromeres)
            essential 2.0%
            non-essential 1.0%%
      telomeres
            essential (less than 1000 kb, insignificant)

Intergenic DNA (not included above)
      conserved 2% (essential)
      non-conserved 26.3% (unknown but probably junk)

Total Essential/Functional (so far) = 8.7%
Total Junk (so far) = 65%
Unknown (probably mostly junk) = 26.3%

For references and further information click on the "Genomes & Junk DNA" link in the box

LAST UPDATE: May 10, 2011 (fixed totals, and ribosomal RNA calculations)

---

November 11, 2006
Sea Urchin Genome Sequenced

The sea urchin genome is 814,000 kb or about 1/4 the size of a typical mammalian genome. Like mammalian genomes, the sea urchin genome contains a lot of junk DNA, especially repetitive DNA. The preliminary count of the number of genes is 23,300. This is about the same number that we have in our genomes. Only about 10,000 of these genes have been annotated by the sea urchin sequencing team.

How to Be a Grown-up Scientist

 
Janet Stemwedel has put her finger on an important issue. Read her blog and find out about The project of being a grown-up scientist (part 1).

What percentage of academic scientists are grown-ups? I think it's pretty high in my department but it's not 100%.

---

TV Ontario's Best Lecturers

 
It's that time of year again. TV Ontario (TVO) has chosen its ten finalists for best university lecturer. you can see the list on the Best Lecturer website.

Some of you might recall that Michael Persinger of the magic motorcycle helmet was one of the finalists last year and he went on to win the $10,000 prize [TV Ontario's Best Lecturers]. I was a bit peeved at this. I wrote,

This is a popularity contest. The last one was very disappointing because some of the most important aspects of being a good university lecturer were ignored.

I'm talking about accuracy and rigour. It's not good enough to just please the students. What you are saying has to be pitched at the right level and it has to be correct. Too many of the lectures were superficial, first-year introductions that offered no challenge to the students. (One, for example, was an overview of Greek and Roman architecture by an engineering Professor.) The students loved it, of course, and so did the TV producers because they could understand the material. Lecturer's in upper level courses need not apply.

Some of last year's lectures were inaccurate. The material was either misleading or false, and the concepts being taught were flawed. Neither students nor TV audiences were in any position to evaluate the material so accuracy was not a criterion in selecting the best lecturer of 2006.

I wrote to the producers about this, suggesting that the lecturers be pre-screened by experts in the discipline. TV Ontario promised to do a better job this year. I'm looking forward to seeing if they keep their promise.

Are you wondering how they did? They chose Michael Persinger, a "fringe" scientist, to put it politely.

How are they doing this year? Here's the list of judges.

Zanana L. Akande (born 1937 in Toronto, Ontario) is a former Canadian politician. She was the first black woman elected to the Legislative Assembly of Ontario, and the first black woman to serve as a cabinet minister in Canada.

Barry Callaghan has done work in journalism, television, and filmmaking in addition to his own writing. He began his career as a part-time reporter for Canadian Broadcasting Corp (CBC) television news and gave weekly book reviews on the CBC radio program Audio.

Tony Nardi is an actor/ writer/producer. His acting experience has been diverse and prolific, in live theater, television and film. As an actor he received his training in Montreal at the Actor's Studio, The Banff School of Fine Arts, The Stratford Festival, and Italy.

Isn't that interesting. The best people to judge whether a university Professor is delivering a good lecture are a politician, a writer, and an actor.

Silly me. I thought that Professors might be on the panel of judges. I guess they're all too busy serving on juries that evaluate politicians, writers, and actors.

The top three criteria for evaluating university lectures are: (1) accuracy, (2) accuracy, and (3) accuracy. The only people who can judge whether those criteria are being met are other academics in the same discipline. If the lectures aren't accurate then nothing else matters. If the lecture material is accurate then you can start looking at other things, such as style.

---

Who Put the Cephalopod in SEED Magazine?

 
SEED magazine is usually a pretty good magazine in spite of the fact that they get a few things wrong and in spite of the fact that they sponsor ScienceBlogs^TM.

But enough is enough. Imagine my surprise when I opened the current issue (January/February 2008) to page 21 and saw this ugly, squishy, creature. As a (fairly) loyal reader, I've been tolerant of their graphics and images even though most of them don't make much sense. But this is way over the top. Did the editors forget that this magazine is displayed on news stands where young children might see it?

Who is responsible for this? And what can we do about it?

---

[Hint: The disgusting image seems to be associated with an article titled Eyeing the Evolutionary Past by Paul Z. Mierz.]

Nobel Laureate: François Jacob

 

The Nobel Prize in Physiology or Medicine 1965.

"for their discoveries concerning genetic control of enzyme and virus synthesis"

François Jacob (1920 - ) received the Nobel Prize in Physiology or Medicine for his work on gene expression. He shared the prize with André Lwoff and Jacques Monod. The three men worked together at the Institut Pasteur in Paris, France, at a time when it was one of the leading centers of research in this field.

Jacob made major contributions to the discovery of messenger RNA and the regulation of transcription when these processes were just beginning to be understood. His name, and Monod's, are mostly associated with the lac operon in E. coli but the prize was also given for work with bacteriophage. The concepts of operons, operators, and repressors all come from the work of Jacob and Monod.

THEME:

Nobel Laureates
The presentation speech was given by Professor Sven Gard, member of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute. As you read it, note how much they knew in 1965 after only a few years of intense work in deciphering the genetic code and working out how genes are transcribed. This is only 12 years after Watson & Crick's paper on the structure of DNA. That's the same amount of time that has elapsed between 1996, when Dolly the sheep was cloned, and today.

Your Majesties, Royal Highnesses, Ladies and Gentlemen.

The 1965 Nobel Prize in Physiology or Medicine is shared by Professors Jacob, Lwoff and Monod for «discoveries concerning the genetic regulation of enzyme and virus synthesis».

This particular sphere of research is by no means easy. I heard one of the prize winners, Professor Jacob, forewarn an audience of specialists more or less as follows: «In describing genetic mechanisms, there is a choice between being inexact and incomprehensible». In making this presentation, I shall try to be as inexact as conscience permits.

It has become progressively more apparent that the answer to what has hitherto been romantically termed the secret of life must be sought in the mechanism of action and in the structure of the hereditary material, the genes. This central field of research has naturally been approached from the periphery and in stages. Only in recent years has it been possible to make a serious attack on these fundamental problems.

Several previous Nobel Prize holders: Beadle, Tatum, Crick, Watson, Wilkins, Kornberg and Ochoa have worked in this sphere of research and have formulated certain basic proposals which have enabled the French scholars to continue their efforts. It has been established that one of the principal functions of genes must be to determine the nature and number of enzymes within the cell, the chemical apparatus which controls all the reactions by which the cellular material is formed and the energy necessary for various life processes is released. There is thus a particular gene for each specific enzyme.

In addition, some light has been thrown on the chemical structure of genes. In principle, they have the form of a long double chain consisting of four different components, which can be designated by the letters a, c, g, and t, and with the property of forming pairs with each other. An «a» in one of the chains has to be matched by a «t» in the other, a «g» only by a «c». However, they can be linked along the length of the chain in any order whatsoever, so that the number of possible combinations is virtually unlimited. A chain of genes contains from several hundreds to many thousands of units; such structures can easily carry the specific patterns for the million or more genes which it is estimated that a cell may have.

This model of the genes represents a coded message containing two types of information. If the double chain of a gene is split lengthwise and each half acquires a new partner, then the final result is two double chains identical to the original gene. The model thus contains information relative to the actual structure of the gene, which permits multiplication, in its turn a condition of heredity. When a cell divides, each daughter cell receives an exact copy of the parent gene. The structure of the double chain ensures the stability and permanence required by hereditary material.

But the model can also be read in another way. Along the length of the chain, the letters are grouped in threes in coded words. An alphabet of four letters allows the formation of more than 30 different words and the sequence in the gene of such words provides the structural information for an enzyme or some other protein. Proteins are also chain molecules built up from twenty or so different types of building blocks. To each of these building blocks there corresponds a chemical code word of three letters. The gene thus contains information on the number, nature, and order of the building blocks in a particular protein.

Thus it was already clear that the hereditary blueprint contained the collective structural information for all substances necessary for the functions of the living cell. It was not known how the genetic information was put into effect or transformed into chemical activity. As to the function of the genes, it was thought that they participated in a sort of procreative act when the new cell came into being, producing new substances necessary for the life of the cell, but subsequently lying dormant until the next cell division. It was presumed that the structure and formation of the chemical apparatus determined in this way defined all the regulatory mechanisms necessary for the cell's ability to adapt to changes in the environment and to respond in an adequate manner to stimuli of different types.

To begin with, the group of French workers were able to demonstrate how the structural information of the genes was used chemically. During a process resembling gene multiplication an exact copy of the genetic code is produced, termed a messenger. The latter is then incorporated into the chemical «workshop» of the cell and wound like magnetic tape onto a spool. For each word arriving on the spool, a constructional unit is attracted, which carries a complement to this word and attaches itself there just like a piece of jigsaw puzzle. The building blocks of a protein are selected in this way one by one, aligned, and joined together to form a protein with the appropriate structure.

The messenger substance is, however, short-lived. The tape lasts only for a few recordings. The enzymes are also used up in a similar way. For the cell to maintain its activity, it is thus necessary to have an uninterrupted production of the messenger material, that is to say continuous activity of the corresponding gene.

However, cells can adapt themselves to different external conditions. Thus there must exist some mechanisms controlling the activity of the genes. The research into the nature of these mechanisms is a remarkable achievement which has opened the way for the possible explanation of a series of hitherto mysterious biological phenomena. The discovery of a previously unknown class, the operator genes, which control the structural genes, marks a major breakthrough.

There are two types of operator genes. One type releases chemical signals, which are perceived by a second, receptor, type. The latter controls in its turn one or more structural genes. As long as the signals are being received the receptor remains blocked and the structural genes are inactive. Certain substances coming from outside or formed within the cell can, however, influence the chemical signals in a specific manner, changing their character so that they can no longer influence the receptor. The latter is unblocked and activates the structural genes; messenger material is produced and the synthesis of enzymes or another protein commences.

Control of gene activity is thus of a negative nature; the structural genes are only active if the repressor signals do not arrive. One can speak here of chemical control circuits similar in many ways to electrical circuits, for example in a television set. In the same way, they can be interconnected or arranged in a series to form complicated systems.

With the aid of such control circuits, the free living monocellular organism can produce enzymes when required, or interrupt chemical reactions if they are likely to cause damage; an excitatory stimulus can provoke movement, flight or attack, depending on the nature of the excitation. With such mechanisms it is possible to direct the development of cells into more complicated structures. It is particularly interesting to note that the activity of viruses is controlled, in principle, in the same manner.

Bacteriophages contain a genetic control circuit complete with emitter, receptor, and structural genes. While chemical signals are being sent and received, the virus remains inactive. When incorporated into a cell, it behaves like a normal component of the cell, and can confer on it new properties which may improve its chances of survival in the struggle for existence. However, if the signals are interrupted, the virus is activated, starts to grow rapidly and soon kills the host cell. There is considerable evidence for the view that certain types of tumor virus are incorporated into a normal cell in the same way, thus transforming it into a tumour cell.

We are easily inclined to hold an exaggerated opinion of ourselves in this era of advanced technology. Thus, we are justified in having a great admiration for the achievements in electronics, where, for example, the attempts at miniaturization to reduce component size, to lower the weight, and reduce the volume of apparatus have enabled a rapid development of space science. However, we should bear in mind that, millions of years ago, nature perfected systems far surpassing all that the inventive genius of man has been able to conceive hitherto. A single living cell, measuring several thousandths of a millimetre, contains hundreds of thousands of chemical control circuits, exactly harmonized and functioning infallibly. It is hardly possible to improve on miniaturization further; we are dealing here with a level where the components are single molecules. The group of French workers has opened up a field of research which in the truest sense of the word can be described as molecular biology.

Lwoff represents microbiology, Monod biochemistry, and Jacob cellular genetics. Their decisive discovery would not have been possible without competence and technical knowledge in all these fields, nor without intimate cooperation between the three researchers. But the mystery of life is not resolved simply with knowledge and technical skill. One must also have a gift for observation, a logical intellect, a faculty for the synthesis of ideas, a degree of imagination, and scientific intuition, qualities with which the three workers are liberally endowed.

Research in this field has not yet yielded results that can be used in practice. However, the discoveries have given a strong impetus to research in all domains of biology with far-reaching effects spreading out like ripples in the water. Now that we know the nature of such mechanisms, we have the possibility of learning to master them, with all the consequences which that will surely entail for practical medicine.

François Jacob, André Lwoff, Jacques Monod. Thanks to your technically unimpeachable experiments and your ingenious and logical deductions, you have gained a more intimate familiarity with the nature of vital functions than anyone before you has done. Action, coordination, adaptation, variation - these are the most striking manifestations of living matter. By placing more emphasis on dynamic activity and mechanisms than on structure, you have laid the foundations for the science of molecular biology in the true sense of the term. In the name of the Caroline Institute, I ask you to accept our admiration and our most sincere congratulations. Finally, I invite you to come down from the platform to receive the prize from His Majesty the King.

---

Gods Behaving Badly

 
Gods Behaving Badly is a new book by Marie Phillips. It was just reviewed in the New York Times [The House of Myth]. Here's a teaser,

Americans have long delighted in movies like ''It's a Wonderful Life,'' ''Heaven Can Wait'' (both the 1943 and 1978 versions) and ''Bruce Almighty'' -- ''divine comedies,'' to borrow the marketing shtick of the day, in which a benevolent male Judeo-Christian God and sometimes his demonic counterpart are represented by stock imagery like billowing clouds, bolts of lightning, bumbling plainclothes angels and horned creatures thumping pitchforks. The humor may be irreverent, but it's always delivered with a basic attitude of respect.

Such deference, a holdover perhaps from the days of the Hays Code, is entirely lacking in Marie Phillips's first novel, ''Gods Behaving Badly,'' in which the 12 major deities of ancient Greece uneasily cohabit in a dilapidated town house in 21st-century London, dwelling just above the city's ''greasy tide'' of human flesh. It's like Hesiod's ''Theogony'' meets MTV's ''Real World.''

In the author's affectionate telling, Zeus, the fading patriarch, is squirreled away on the top floor; Apollo is a horny and malcontented television psychic; and Aphrodite is a phone-sex worker whose buttocks, when she mounts a staircase, resemble ''two hard-boiled eggs dancing a tango'' -- maybe the most original description of the female posterior since Jerry approvingly deemed Sugar Kane's ''Jell-O on springs'' in ''Some Like It Hot.'' Apollo's virginal, pragmatic twin sister, Artemis, walks dogs for a living and jogs compulsively in her spare time. Dionysus owns a nightclub called Bacchanalia and is constantly plugged in to a music player. Meanwhile, Athena has been cast as an efficient boardroom type who distributes handouts to her bored family as she subjects them to streams of corporate gobbledygook.

This sounds like a terrific book. I don't normally read fiction—other than creationist books—but this will be an exception. Has anyone read it?

---

What Happened to the "Peers" on this Paper?

 

Quite a few science bloggers were shocked at a paper that appeared recently in the journal Proteomics—a respectable journal up 'till now.

PZ Myers had the stomach to blog about this train wreck of a paper. Read his article at A baffling failure of peer review.

---

[Photo Credit: Train Wreck at Gare Montparnasse, Paris, France, 1895 from Answers.com]

Joshua Lederberg

 

Joshua Lederberg died last Saturday (Feb. 2, 2008). In his honor, John Dennehy has selected one of Lederberg's famous papers as This Week's Citation Classic: Joshua Lederberg.

I think it's too bad that our current generation of students is growing up without being sufficiently aware of the fundamental principles of biochemistry and molecular biology that were worked out in bacteria and bacteriophage.

UPDATE: [Loss of a giant: Joshua Lederberg]

---

Tangled Bank #98

 
The latest issue of Tangled Bank is #98. It's hosted by Steve Matheson at Quintessence of Dust [Tangled Bank #98].

Hey! Welcome to Tangled Bank #98, and thanks for stopping by. If you've never been to Quintessence of Dust, the lobby is below and to the right. I hope you'll poke around a little.

PZ didn't give me a budget for refreshments, but if you come to the house I'll make sure we at least have plenty of guacamole. Chips are here, and beer is over there. Our city was once used by Anne Lamott as a metaphor for plainness, but it's much cooler than most people think. You can get to our house on a nice bus system, and after the carnival we can pick one of two Ethiopian restaurants. My day job is at Calvin College, but right now I'm on sabbatical in the lab of a friend and collaborator at the Van Andel Institute in downtown Grand Rapids.

---

If you want to submit an article to Tangled Bank send an email message to host@tangledbank.net. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger. For some of you that's going to be a serious problem. You have to pick your best article on biology.

Evolution as Tinkering

François Jacob won the Nobel Prize in 1965 for his work on the lac operon. He is also known for his thoughts on evolution, especially the concept of a tinkerer. The idea deserves to be better known so I present a long quotation from his little book The possible and the Actual published in 1994. The book contains a lecture that was based on an article he published in Science back in 1977 (Jacob, 1977).

I'm a big fan of this view of evolution [Evolution by Accident].

The action of natural selection has often been compared to that of an engineer. This comparison, however, does not seem suitable. First, in contrast to what occurs during evolution, the engineer works according to a preconceived plan. Second, an engineer who prepares a new structure does not necessarily work from older ones. he electric bulb does not derive from the candle, nor does the jet engine descend from the internal combustion engine. To produce something new, the engineer has at his disposal original blueprints drawn for that particular occasion, materials and machines specially prepared for that task. Finally, the objects thus produced de novo by the engineer, at least by a good engineer, reach the level of perfection made possible by the technology of the time.

In contrast, evolution is far from perfection, as was repeatedly stressed by Darwin, who had to fight against the argument from perfect creation. In the Origin of Species, Darwin emphasizes over and over again the structural and functional imperfections in the world. He always points out the oddities, the strange solutions that a reasonable God would never have used.

In contrast to the engineer, evolution does not produce innovations from scratch. It works on what already exists, either transforming a system to give it a new function or combining several systems to produce a more complex one. Natural selection has no analogy with any aspect of human behavior. If one wanted to use a comparison, however, one would have to say that this process resembles not engineering but tinkering, bricolage we say in French.

While the engineer's work relies on his having the raw materials and the tools that exactly fit his project, the tinkerer manages with odds and ends. Often without even knowing what he is going to produce, he uses whatever he finds around him, old cardboards, pieces of string, fragments of wood or metal, to make some kind of workable object. As pointed out by Claude Levi-Strauss, none of the materials at the tinkerer's disposal has a precise and definite function. Each can be used in several different ways. What the tinkerer ultimately produces is often related to no special project. It merely results from a series of contingent events, from all the opportunities he has to enrich his stock with leftovers. In contrast with the engineer's tools, those of the tinkerer cannot be defined by a a project. What can be said about an of these objects is that "it could be of some use." For what? That depends on the circumstances.

In some respects, the evolutionary derivation of living organisms resembles this mode of operation. In many instances, and without any well-defined long-term project, the tinkerer picks up an object which happens to be in his stock and gives it an unexpected function. Out of an old car wheel, he will make a fan; from a broken table, a parasol. This process is not very different from what evolution performs when it turns a leg into a wing, or a part of a jaw into pieces of ear.

...

When different engineers tackle the same problem, they are likely to end up with very nearly the same solution: all cars look alike, as do all cameras and all fountain pens. In contrast, different tinkerers interested in the same problem will reach different solutions, depending on the opportunities available to each of them. This variety of solutions also applies to the products of evolution, as is shown, for instance, by the diversity of eyes found throughout the living world. The possession of light receptors confers a great advantage under a variety of conditions. During evolution, many types of eyes appeared, based on at least three different principles: the lens, the pinhole, and multiple holes. The most sophisticated ones, like ours, are lens-based eyes, which provide information not only on the intensity of incoming light but also on the objects that light comes from, on their shape, color, position, motion, speed, distance, and so forth. Such sophisticated structures are necessarily complex.

One might suppose, therefore, that there is just one way of producing such a structure. But this is not the case. Eyes with lenses have appeared in molluscs and in vertebrates. Nothing looks so much like our eye as the octopus eye. Yet it did not evolve the same way. In vertebrates, the photoreceptor cells of the retina point away from the light while in molluscs they point toward the light. Among the many solutions found to the problem of photoreceptors, these two are similar but not identical. In each case, natural selection did what it could with the materials at its disposal.

For a more up-to-date view of the evolution of eyes see PZ Myers' article in the current (January/February 2008) issue of SEED magazine.

---

Jacob, F. (1977) Evolution and Tinkering. Science 196:1161-1166. ]JSTOR]

Jacob, F. (1994) from The Possible and the Actual, reprinted in Evolution Extended, Connie Barlow ed. MIT Press, Cambridge, MA (USA) 1994.

The Streisand effect

 
This is a new term to me. It was used over on simra.net in reference to the attempt by students at Wilfred Laurier University to dictate to the Laurier Freethought Alliance [Follow-up on the WLU controversy]. I had to look up the term on Wikipedia.

Just in case there are any other old people out there, here's the definition.

The "Streisand effect" is a term used to describe a phenomenon on the Internet where an attempt to censor or remove (in particular, by the means of cease-and-desist letters) a certain piece of information (for example, a photograph, a file, or even a whole website) backfires. Instead of being suppressed, the information receives extensive publicity, often being widely mirrored across the Internet, or distributed on file-sharing networks in a short period of time.[1][2] Mike Masnick said he jokingly coined the term in January 2005, “to describe [this] increasingly common phenomenon.”[3] The effect is related to John Gilmore's observation that, "The Net interprets censorship as damage and routes around it."

The term Streisand effect originally referred to a 2003 incident in which Barbra Streisand sued photographer Kenneth Adelman and Pictopia.com for US$50 million in an attempt to have the aerial photo of her house removed from the publicly available collection of twelve thousand California coastline photographs, citing privacy concerns.[4][5][1] Adelman claims he was photographing beachfront property to document coastal erosion as part of the California Coastal Records Project.[6] Paul Rogers of the San Jose Mercury News later noted that the picture of Streisand’s house was popular on the Internet.

---

The Quacks Fight Back

 
Last week David Colquhuon gave a talk sponsored by the Centre for Inquiry and the University of Toronto Secular Alliance [Quackery in Academia] [Science in an Age of Endarkenment].

During his visit to Toronto he was interviewed by Michael Enright of the CBC Radio show The Sunday Edition. The interview was broadcast on Sunday, January 27th. As you might imagine, there were lots of comments and emails and a second show was required in order to restore some "balance." The second show was broadcast on Sunday, February 3rd [The Sunday Edition].

A stirred-up hornet's nest is a mild disturbance compared to the firestorm we unleashed last week over my conversation with Dr. David Colquhoun. Dr. Colquhuon is a gangly, pipe-puffing British pharmacologist who thinks all alternative medicine, all of it, is a fraud perpetrated by quacks. But he went further, somehow suggesting that those who believe in it probably supported Margaret Thatcher, Ronald Reagan and the Ayatollah Khomeini. He pooh-poohed acupuncture, chiropractic, homeopathy, even vitamins.

Well, his remarks opened the floodgates of listener mail, screaming for Dr. Colquhoun's head on a pike. In a few moments, alternative or complimentary medicine strikes back. With the help of two experts, we will try to give the other side of contentious Colquhounism.

Two quacks were required to restore the rift in the space-time continuum caused by too much rationality: Dugald Seely of the Canadian College of Natrupathic Medicine and Dr. Kien Trinh of the DeGroote School of medicine at McMaster University in Hamilton. It's shocking that one of them is from a genuine medical school: he's in a Ph.D. program.

You can listen to the podcast on the CBC website but I can assure you that you won't learn anything new. There's some important issues here. Here's one of the letters that was read on the show ...

Most proponents of alternative medicine do not deny the place of Western medicine. It is too bad that for some the respect is not reciprocal.
                                 Dale Jack

The logic here is that just because some quacks are able to recognize the value of evidence-based medicine then it follows that scientists should extend the same respect to quacks who promote non-evidence-based medicine.

It's a mark of how silly our society has become that such an argument even merits a response. It would be like saying that the most outlandish ideas deserve equal time as long as their proponents are respectful to the proponents of reality.

Here's a similar comment ...

He [Colquhoun] is the very representative of the darkness of the scientific method. He is one of the very ilk that would have driven the new hand-washing surgeons to suicide. As a past-President of the Complementary and Integrative Physicians of B.C., I do hope you will spend the next few weeks in contrition—to re-establish your usually balanced and worthwhile reputation.
                                 Steven Faulkner

Coming from a quack, I guess we shouldn't be surprised at the "logic" exhibited here. The first example is the old saw about truly brilliant innovators who were originally scoffed at. The idea is that because one person took on the scientific establishment and won, it follows logically that all renegades must be right. Conversely, scientists who scoff at quacks must be wrong.

No, this does not compute. As they say, people laughed at Galileo but they also laughed at Bozo the clown.

The second example of silly logic is the concept of "fairness" and "balance" that is used time and time again by quacks and IDiots. Apparently it doesn't matter how stupid your ideas are, society demands that you be given a hearing if you are attacked. Well I've got news for all you quacks out there. You don't get to promote your crazy ideas just because you have them. There's no rule that says you have to be given a platform on public radio just because you've been criticized.

If you want to be heard go the Hyde Park on a Sunday morning. Take a soapbox.

---