From Weed to Maize

A large-scale investigation on the evolution of corn finds lots of regulatory change.

When Darwin wrote his book on the origin of species, his strongest examples came from pigeons, which at the time were very popular domesticated animals. Just like dogs and cats, pigeons displayed a profusion of breeds and characteristics, all quite clearly descended from a single progenitor species, by way of artificial selection. The speed of artificial selection is amazing, but its relentless focus on desired, superficial traits can lead to problems in temperament, disease susceptibility, and subtle congenital defects.

As mentioned in a recent post, most evolutionary change takes place in regulatory relationships within the genome, rather than as structural changes in encoded proteins. Fine-tuning the binding site of some transcriptional regulator, or moving its site nearer or farther from a gene, tends to have smaller, graded effects on the organism than a change, for example, to that same transciption regulator's own protein sequence, which may affect its interaction with to thousands of sites all over the genome.

A recent paper took a deep dive into the changes that happened in the maize genome on its way to our tables as the king of American agriculture. They reiterate the power of small scale change in a gene's regulatory elements, which they term the cis elements, which is to say, mutations in the DNA local to the gene, typically in upstream sites that bind various regulatory proteins which promote or repress transcription.

"Changes in the cis regulatory elements (CREs) of genes with functionally conserved proteins have been considered a key mechanism, if not the primary mechanism, by which the diverse forms of multicellular eukaryotic organisms evolved. Variation in CREs allows for the deployment of tissue specific patterning of gene expression, differences in developmental timing of expression, and variation in the quantitative levels of gene expression. Furthermore, modification of CREs, as opposed to coding sequence changes, are assumed to have less pleiotropy and consequently have a lower risk of unintended deleterious effects in secondary tissues. The importance of CREs for the development of novel morphologies is supported by the growing catalog of examples for which differences in gene specific CREs between closely related species contributed to the evolution of diversity in form."

The authors sequenced a large crop of RNAs from the tissues of maize and from its ancestor teosinte, to see how their genes are expressed, and, in combination with knowing the genomic DNA that had been sequenced previously, whether changes in gene expression could be tied to specific genome mutations that happened during domestication. The maize genome has more genes than that of humans, 39,423, and 17,579 of them had sufficient expression in these tissues (the RNAs came from the immature ear, the seedling leaf, and the seedling stem) to be analyzed. To give an idea of the scale of current technology, they gathered roughly four billion sequence reads from their RNA libraries.

The majority of the genes they analyzed (82%) were expressed in each of three tissues, while about three percent each were specific to only one or two tissues. The main point of the paper was to attempt to figure out which genes had changed in expression between teosinte and maize, and further, what had caused this, either mutations local to the altered gene, (acting in "cis"), or mutations to DNA far away (acting in "trans") that encodes regulatory proteins whose alteration would affect many other genes as well.

To do that, they used hybrids between teosinte and maize, sampling their RNA as well. In these hybrids, versions of the same gene (alleles) from each parent co-habit in the same cell. So if their expression remained different, it could be chalked up to local effects on each allele's DNA. Conversely, if their expression became similar, (while being different in the parental strains), then the parental difference is likely to be due to regulators that are encoded elsewhere and affect the sampled gene similarly, whatever its origin and local sequence. A very clever scheme, one has to say.

Master graph of genes (dots) assigned to categories of regulatory change, either local to the gene sequence (cis, in black), or due to changes in a non-local regulator (trans, in red). The conclusion is based on the gene's respective behavior when co-housed in the same plant, i.e. the hybrid progeny of a maize X teosinte cross. The logs on each axis refer to logs of the ratio between maize and teosinte, in either the parents (X axis) or in the hybrids (Y axis).

The identity / parentage of the alleles in the hybrids could be kept straight by way of minor DNA variations sprinkled throughout the sequences of their expressed RNA. Teosinte and maize have been separated by about eight thousand years, enough time for quite a few (mostly silent) mutations to accumulate in each genome. But the interesting differences between them would be those that were specifically selected in maize to make it into the dramatically different plant it is today- stalk branching, ear size, ear morphology, growing speed, hardness of the seed, etc. What were those mutations and how can they be found? This paper unfortunately does not get to that detail. They note that 70% of all the genes showed significant changes in expression, and that the sets of differently expressed genes were ~70% different in each of the three tissues. All of which is quite remarkable.

What they are more interested in is defining large sets of genes that might be interesting as ingredients of the special properties of maize. To start, they assume that genes under selection pressure would have had local changes to their regulatory DNA. This is not entirely correct, though. Some far-away change might have been selected for if it had strong effects regulating some target gene / trait, without having too many side effects. While this is difficult to imagine and likely rare, it is by no means impossible or without precedent. Nevertheless, they bundle up all the genes with local or local + distant changes, and call them their "CCT" set (for cis and cis+trans changes in regulation profile). These are the black and purple dots on the graph above, and amounted to about 5500 genes.

They further filtered that set by asking for high consistency and high expression over all their samples, (or different parental and hybrid cross strains), and came up with sets of varying stringency, from very few (69) genes to a much less stringent set (~2326) genes. This had the defect of discounting genes whose expression was very low, either before (in teosinte), or after (in maize). Anyhow, it was a rough-and-ready method to whittle down their data to some interesting candidate genes, depending on how stringently they set the dials. One problem was that gene expression is naturally more variable in teosinte, being a genetically diverse and wild plant, (despite their using inbred strains, which must not have been quite as inbred as they thought), than it is in maize, being heavily in-bred and virtually clonal.

The larger the expression difference of a gene between teosinte and maize (X axis), the more likely that difference is due to local "cis" regulatory effects (Y axis). This is reflected also in the previous graph of genes with higher expression differences on the higher slope lines.

The rest of the paper, unfortunately, is a litany of woe, as they find that their sets of specially selected genes do not agree very well with those that other researchers have isolated using other methods. For instance, one group used a micro-chip based method with fixed DNA samples detect RNAs that are expressed differentially between modern maize and teosinte, and found their own list of such genes:

"However, the absolute level of correspondence between the two studies is rather low. For example, of the 350 leaf genes identified as DE [differentially expressed] by RNAseq [the current paper's method], only 24 (7%) were also identified by the microarray study [the other paper's method]. Thus, while the overlap between our two studies is statistically significant, the two methodologies resulted in largely different lists of DE genes."

It is somewhat depressing that this many years into the genomic age, the large-scale technologies being touted and used to gather presumably quantitative gene expression data of this sort can generate such divergent results. Technically, I believe this is due to their need to have high expression under all conditions, which is contrary to most of the other methods used, which prize very high contrast, i.e. very low expression in one sample vs higher expression in another, to identify candidate genes. Nevertheless, each collection of genes must have some gold amongst the placer and thus this paper is surely the career-building effort of some post-doc who will give job interviews on the ambition of panning through these genes to find ones that have individually significant effects on the unique properties of maize.

"This study shows cis and trans regulatory differences account for ~45% and ~55% of regulatory divergence between maize and teosinte, respectively (Table S1). These values suggest relatively equal contributions of these two mechanisms to regulatory divergence. However, this ignores the contribution of cis effects to large expression differences where cis accounts for nearly 80% of the expression divergence."

A final interesting point is that roughly half the expression differences were traceable to the "trans", or non-local, mechanism. This might seem to go against the assumption outlined above that local mutations in gene regulatory sequences should predominate, but it may take only a few individual changes in regulators or their networks to cause changes in the expression of many of the genes assayed here, while each expression change classified as "cis" or local requires a separate change to that gene's sequence. So the overall number of local regulatory changes in this data set will vastly outnumber individual changes elsewhere, and the authors note additionally that the expression changes that were quantitatively highest were virtually all due to local mutations.

• Similar story for the deeper divergence between mouse and human.
• Has religion outlived its usefulness?
• Reza Aslan: No, and let me present a diatribe about that.
• A notable podcast on the role of philosophy, relations to science, and ... is there progress?
• Inheritance ... another feudal, antisocial practice.
• Perjury- the new frontier in mortgage fraud.
• Banking is a immoral industry. Perhaps a proper target of vice squads?
• CO2 visualized, world-wide.
• Target zero for carbon emissions.
• Some power companies are on board.
• Just what was China promising?
• Britain has internet service competition, we do not.
• Just what is wrong with the muslim world? Why the torpor, humiliation, and tragedy?
• Why is the Fed backing off?
• Democracy may require some kind of revolt.
• This week in the WSJ- the 1% "earners" are OK.
• But Bill Black thinks otherwise:

"Cochrane admits in the final paragraph that one of the “secrets of prosperity” is a well-functioning “rule of law.” He doesn’t tell you that his institution, the University of Chicago’s law, finance/business, and law faculty, have led the systematic attack for the last 40 years that successfully eviscerated that rule of law and allowed the banksters to lead the fraud epidemics that Cochrane admits drive our recurrent, intensifying financial crises."

Wave of in-Attention

The visual system uses rhythmic synchrony to gate data to higher levels.

While it is clear that the brain creates our mind, the vast mechanism linking the two remains mysterious in many respects. The connection is attested by countless conditions and experiments, more or less tragic, but while the science has been progressing well, the brain is an inscrutible organ, and much remains to be done.

A recent paper describes coordinated fMRI and EEG experiments on humans to tell whether top-down attention uses the mechanism of brain waves to filter visual processing coming up from the sensory system, so that we can look at what we want. The attention system is very interesting and perhaps not commonly understood. The executive areas of the brain reach back into all the sensory areas and elsewhere, such that information processing is a two-way street. Signals from the senses do not just all flood into consciousness at the same time, but we attend to one or another, and that requires not only filtering against all the other streams of incoming data, but also management of the active stream, to focus on what we are "interested" in. Indeed, with no sensation at all, we can, though the attention process, imagine a sensory stream, which actually animates the sensory regions involved to create an attenuated, but physically accurate, stream of internally-generated "sensation" information.

The researchers here were interested in the correlation between mental activity, particularly in the visual areas, and brain wave activity. They were looking at alpha waves, (7-12 kHz), not the gamma wave activity that has been associated (loosely) with consciousness. Alpha waves are known to be associated with relaxed, non-processing, but ready, states. The primary example is the visual (occipital, rear) area of the brain, with eyes closed and the subject relaxed but awake. The waves then decline in power / coherence when eyes are opened and a visual scene is being actively processed. Other forms of the alpha wave are strong in specific areas and kinds of sleep.

"... several studies using transcranial magnetic stimulation and visual entrainment of 10-Hz activity have demonstrated that the alpha rhythm plays a causal role in the allocation of attention, perception, and working memory maintenance."

Not surprisingly, the researchers found an inverse correlation between alpha waves and the attention someone is paying in a part of a visual scene. This suggests that alpha waves are used to quiet the waters in unattending areas, rather than to synchronize or convey data, as has been thought for other wave patterns. The unattending areas are still working and processing their visual fields, but they are closed off from attention and consciousness, more or less.

Visual processing pathway, showing how visual hemifields map to the respective occipital cortex hemispheres.

The setup was to place human subjects in an MRI machine, with EEG electrodes attached as well. They were shown visual images that had two parts, a left side and a right side. The left side (coming from each eye) maps in the brain to a left "hemifield", which is processed in the right side of the brain. The researchers instructed the subjects to pay attention to one or the other side, though images were presented to both sides. The attention was enforced by asking/testing whether the image was the same or different than a previous one.

Example of images presented to the subjects, where attention was directed to one or the other side (hemifield; arrows). This implies that the subject's eyes were kept straight ahead, focused on the center "X".

So the subjects were staring at a full visual field, but spent a couple of seconds attending (mentally) to one or the other side, either a face or a landscape. The MRI showed increased activity (i.e. blood flow) on the corresponding side of the brain's visual processing area, the occipital lobe at the back. It also showed increased activity in the facial recognition area (for faces; fusiform face area) or in a place recognition area (for landscapes; parahippocampal place area).

But the alpha wave pattern in the EEG consistently showed lower power in the areas active above, and higher power in the corresponding areas in the other hemisphere- the hemisphere where attention was not being focused.

Alpha wave power during directed visual attention, reflected by higher MRI signal on the R side, corresponding to attention to the Left visual hemifield. Alpha power is dramatically reduced as attention is being paid.

MRI signal simultaneous with the image above, with higher activity on the attending side (R).

What do they make of all this? They note that "Our findings add support to the notion that alpha band activity serves an active role in the allocation of resources." But not exactly in the way I had expected. As a last project, they look at something called the dorsal attention network, which is thought to be a mechanism where the frontal executive areas reach back to focus attention. This set of regions show similarly inverse MRI correlation with the alpha wave power in the visual area.

"We have demonstrated that the suppression of unattended information is reflected by active inhibition via increased alpha band activity in the unattended visual stream. Our findings add support to the notion that alpha band activity serves an active role in the allocation of resources." 

"We suggest that the mechanism of this gating by alpha activity is via phasic manipulation of higher frequency oscillations in the gamma band. In particular, the increase in alpha activity is important for the routing of information by depressing irrelevant processing of sustained stimulation, which is in stark contrast to the view that posterior alpha activity reflects idling or drowsiness."

Sadly, the work seems quite weak. They basically find that if one directs a person's attention to some item in a visual scene, the corresponding visual region in the brain shows dampened alpha wave activity, while the contralateral area in the other hemisphere shows heightened activity. That part was quite clear. The attention network result was not very strong. And the interpretation of all this is very unclear. Do some waves have something to do with attention and consciousness in some areas of the brain, while other waves at other frequencies and places relate to the opposite? That seems to be the lesson, which thus leaves us waiting for more work and insight into the matter.

• What worries you masters you.
• On the false consciousness of capitalism. "The capitalist marketplace generates a huge amount of anger".
• Same old fraud, same old Citi.
• "The oceans have become 30 percent more acidic over the past 200 years as a result of human activity."
• Which fosters more violence- Hollywood or Islam?
• Amazon goes evil.. towards coal.
• Eco-collapse by neonicotinoids.
• Inflation and growth still needed in Germany.
• Religion vs the internet.
• More on bankers, fraud, corruption, recurring economic catastrophe, etc.
• Why have a legitimate government at all?
• On the Takata story.

We Are the Adaptable Ones

Climate change is about other species, not us.

While all the attempts to calculate the economic costs and benefits of climate change are well-meaning, I think they are mostly beside the point. Of all species on earth, we are the most adaptable, and can readily, if not easily, adapt to climate change. Even if adapting to it eventually costs more than solving it. While other organisms are fated to adapt on evolutionary time, by mutation and selection, (or die), we can adapt in cultural time. Cultural time is hugely compressed vs evolutionary time, as our last century of technical progress, and biosphere destruction, attest.

Earth has gone though very warm epochs in the past, where there were no ice caps, and Alaska had palm trees. And there were great changes to life as a result. But it was all very slow, giving time to the ecological network to adjust. Truly catastrophic events, like the end-Cretaceous asteroid impact, devastated the biosphere to a state that we would never want to see if we can possibly help it. If we have to move to Siberia to farm within a hundred or a few hundred years, we can do so, burning yet more fossil fuel to get there. Other species don't have it so easy.

So I think it is important to avoid, or at least go beyond, the economic, cost vs benefit calculus that many seek to put on the climate change debate. Our current biggest benefit is always to do nothing and hope for the best. The "discount" put on future human generations with respect to benefits they might get from our responsible behavior today is variable and highly subjective. If we feel like doing something for future humans, great. But in any case, we do not face extinction. Other species do.

"A large fraction of species face increased extinction risk due to climate change during and beyond the 21st century, especially as climate change interacts with other stressors (high confidence). Most plant species cannot naturally shift their geographical ranges sufficiently fast to keep up with current and high projected rates of climate change in most landscapes; most small mammals and freshwater molluscs will not be able to keep up at the rates projected under RCP4.5 [an intermediate mitigation scenario] and above in flat landscapes in this century (high confidence). Future risk is indicated to be high by the observation that natural global climate change at rates lower than current anthropogenic climate change caused significant ecosystem shifts and species extinctions during the past millions of years. Marine organisms will face progressively lower oxygen levels and high rates and magnitudes of ocean acidification (high confidence), with associated risks exacerbated by rising ocean temperature extremes (medium confidence)."

"Many terrestrial, freshwater, and marine species have shifted their geographic ranges, seasonal activities, migration patterns, abundances, and species interactions in response to ongoing climate change." 

- the IPCC

Future hothouses on earth, under two different scenarios, first a stringent mitigation scenario, and second a business as usual, high emissions scenario- also from the IPCC.

• Even what are now common species may be wiped out.
• Leave Earth entirely? Not so fast.
• Business people know little about economics.
• But they do know how to steal your lunch.
• On post-capitalism.
• On our post-free-speech world.
• Christians at the polls.
• ... turn out to be bad for America. According to some people.
• Pakistan dislikes being called out, digs deeper hole.

Islam is Not a Religion of Peace

Nor is it a religion of war. A review of the Quran.

Muhammed is the Apostle
Of God; and those who are
With him are strong
Against Unbelievers, (but)
Compassionate amongst each other.
 (48:29)

As scripture, the Quran stands head and shoulders above its relatives in some respects. It is clear, (if tediously long and repetitive), not given to parables and riddles. Nor is it given to obscure genologies and mythical tales (other than a few retold from the Jewish and Christian traditions). It is explicit on many points, giving rules for behavior and hammering home its points about who and what are good and bad. Its general world view is also refreshingly simple. The world's beauty and gifts, especially the wonders of biology, are clear signs of the one god, and one would have to be an idiot or worse to doubt them and thus the Apostle's message, which comes directly from god.

And among His Signs
Is the creation of the heavens
And the earth, and the variations
In your languages
And your colors: verily
In that are Signs
For those who know.
 (30:22)

(The version I am using dates from sixty-eight years ago, well before the political correctness that beset the field since 2001. It is also a version that reads very well and is abundantly annotated. The text runs to 1800 pages.)

The Quran's provinance is also far more secure than those of the other scriptures, being assembled within twenty years of Muhammed's death by order of the rulers of the community. The ancillary Hadith is less secure, but that is another matter. Muhammed's existence is also far better attested than that of the other prophets, from Jesus back to Moses, Abraham, Noah, Adam, and into the mists of time, many of whom, if not all, are mythical, or very heavily mythicised. Muhammed had a very active and well-recorded life, full of commerce, revelation, warfare, and preaching. Indeed, he took special exception to the deification of Jesus, making it a tenet of Islam that Jesus as one of the prior apostles was a normal man with (some) divine inspiration. One might note in passing, however, that the seemingly universal practice of Muslims to never refer to Muhammed without wishing peace be upon him amounts to a furtive deification / sanctification of the apostle. He is most certainly in the finest possible position of heaven by this doctrine, and hardly needs assistance of any kind from the sinners here below.

The Muslim doctrine, aside from a few defects that I will get to, is also a highly moral one, which repeatedly invokes a very simple formula for community membership- belief in god and obedience to his apostle, virtuous moral action, modesty and circumspection in all affairs, and charitable giving to the poor. There are other incidental tasks, such as praying, food restrictions, and the hajj, (incidentally, Islam is about the only modern religion still employing animal sacrifice, which takes place during the hajj), but the basics are admirably simple and doubtless contribute to the attraction of this religion to so many people, and to their self-understanding that it is an almost self-evident doctrine. The Quran also enjoins believers to give charity with open arms and a positive attitude- something that our current Republicans might do well to emulate, our tax system being, in essence, precisely the kind of alms and charity distribution system (plus a little jihad) that Islam envisions.

But some of the desert Arabs
Believe in God and the Last Day,
And look on their payments
As pious gifts bringing them
Nearer to God, and obtaining
The prayers of the apostle.
Aye, indeed they bring them
Nearer (to Him): soon will God
Admit them to His Mercy:
For God is Oft-Forgiving,
Most Merciful
 (9:99)

Unfortunately, Muhammed was faced with a lot of disbelievers in his time, as is reiterated on virtually every page. They are assigned to hell in innumerable ways, sometimes mild, sometimes excruciating. But the repetition of this theme is striking, seeming to signify some insecurity about the clarity and confidence otherwise expressed. Its endless repetition also functions as a sort of hypnotic mantra. Sometimes he takes the mild approach, assuring listeners that, despite the apparent success of unbelievers in this life, with riches and sons, god will mete our their just deserts in the afterlife. But frequently, hatred gets the better of him, and unbelievers are reviled where they are, threatened with various horrible fates in this world, and subject to terror by the (always virtuous) believers. He recurs frequently to the tales of Noah, Moses, Lot, et al. to make clear that unbelievers stand a very good chance of being struck down in this life, en masse, God-willing.

Those who reject
Our Signs, We shall soon
Cast into the Fire;
As often as their skins
Are roasted through,
We shall change them
For fresh skins,
That they may taste
The Penalty: for God
Is Exalted in Power, Wise.
 (4:56)

There is also an odd lack of certainty sometimes, as though the speaker, though being god, isn't entirely sure of some facts or events events. He recounts (18:22) an old Christian story of boys who happened upon a cave and fell asleep there, for a few centuries, only to find on waking that the Christianity that was reviled by the Roman authorities before is now the state religion. Only, the teller of the tale isn't sure whether there were three boys, or five, or seven. It doesn't inspire confidence, frankly. Likewise, he retells the immaculate conception story of Mary having been impregnated by god, but later claims that Jesus was a normal man like all others, not in any way a deity. And that nor did god ever have a son. Logically, it doesn't quite make sense, especially as told by an omniscient being, but makes more sense as a sop to tradition.

Have We not created
You from a fluid
(Held) despicable? 

The which We placed
In a place of rest,
Firmly fixed, 

For a period (of gestation),
Determined (According to need)? 

For We do determine
(According to need); for We
Are the Best to determine (things). 

Ah woe, that Day!
To the Rejectors of Truth!
 (77:20-24)

More generally, the book claims to be full of truths, but the information communicated is meagre. Belief is extolled ad nauseum, as is truth, but no scintilla of knowledge not commonly known at the time is related. This is especially notable in its celebration of biology and the heavens, which are given repeatedly as strong signs of god and his beneficence. Where is the knowledge of breeding, of evolution, of development, and of genetics? (Hey, how about a funny biology song?) The author claims simply that god has made everyone, and can make or unmake people at will. Where is the knowledge of the history of biology and scale the universe? The birth of Adam is recounted as the origin of humanity, in the story of the garden of Eden. As a source of knowledge, the Quran comes off poorly indeed. Imagine how mind-blowing it would have been for an ancient scripture to tell the true story of our origins and nature, taking it as a lesson on the great preciousness and rarity of our existence, and the momentous stewardship we have been granted.

Praise be to God,
Who hath sent to His Servant
The Book, and hath allowed
Therein no Crookedness: 

(He hath made it) Straight
(And Clear) in order that
He may warn (the godless)
Of a terrible Punishment
From Him, and that He
May give Glad Tidings
To the Believers who work
Righteous deeds, that they
Shall have a goodly Reward, 

Wherein they shall
Remain forever:
 (18:1-3)

There are also some theological confusions. God is free of all wants (14:8, and elsewhere), but at the same time wants all kinds of adulation and submission, wants unbelievers to spend eternity in Hell, wants moral behavior in peace and martial behavior in war, indeed, has transmitted a book full of wants.

Pagans and unbelievers are assigned to hell on virtually every page. But they also are promised ill fortune in this life, though sometimes they might do just fine, as god is just staying his hand till some more convenient moment. Indeed, sometimes they are so rich with money and sons that it drives believers positively apoplectic, and to doubt that they are on the right side after all. The Quran tries its best to quiet such doubts, asserting time and again that whatever the current situation, (and however detestable the unbelievers, and whether they may be crushed and destroyed in this world as many other whole tribes have been before by earthquake, flood, or fire, or the sword, or ...), god sees all and will send them to the fire when they die. If not before.

The Santa Claus nature of all this is unmistakable. Charming in its simplicity, but intellectually not at a very high level. God sees all, and will balance all accounts in the final judgement. All the good actions of this life will be rewarded. Except that unbelief seems to cancel them all out. Unbelievers in the Quran can never be good. They are perverse, lying, deceitful, blind, arrogant, mocking ... the list is endless. So the doctrine never has to grapple with the problem of positive moral behavior among non-Muslims. This applies apparently both to the time of death, and to a final judgement, which is mentioned, along with bodily resurrection of the believers, as an evident bow to the Christian system, but is not very well fleshed out, if you will excuse the pun. I could never tell whether I, for example, would go to hell immediately upon death, or whether that would await a general judgement day. The whole thing is, theologically, a jumbled mishmash of past beliefs, and looks much more like a psycho-mechanical contrivance for belief propagation than it is a search for, or convincing explanation of, truth.

O ye who believe!
Ask not questions
About things which,
If made plain to you,
May cause you trouble.
But if ye ask about things
When the Quran is being Revealed,
They will be made plain to you,
 For God is Oft-forgiving,
 Most forbearing.

 Some people before you
 Did ask such questions,
 And on that account
 Lost their faith.
  (5:104-105)

This god is also the most passive-aggressive character in all literature. The signs of his existence are no more than the mundane / glorious / mysterious conditions of nature, which admittedly in Muhammed's day, merited virtually unlimited awe. But if you don't believe in him, (and, notably, obey his humble Apostle), he will get you when you are least aware, and haul you off to everlasting hell fire. On the one hand, the whole Apostle thing comes off as a ego trip without parallel, while on the other, if god were so merciful and powerful, why would Satan (Iblis) be given leave to mislead so many hearts for so much time- why would anyone listen to him and not to god? It makes little sense, other than as a mapping of psychological archetypes onto an imaginary cosmic drama.

This brings up a significant moral point, which is that one would think that with such a fate in store, unbelievers would merit more compassion than they seem to get in the Quran. Why indulge in so much hatred if their fate is so sure and terrible- if they are building in this world their furnace in the next, by all their immoral deeds, unbelief, and mockery? Again, one gets the distinct sense that the theology is not really all that secure, and that the hatred is a very this-world phenomenon oriented to the oldest trick in the book, convincing people to believe in invisible beings, unbelievable doctrines, and the goodness and success of one's own group, led & ruled by God's representative on earth. All for the most admirable reasons, of course, but in a contemporary world that is so dense with other beliefs, yet at the same time contains a billion and half Muslims typically in communities with no contact with unbelievers at all, such attitudes are unhealthy, to say the least. Muhammed himself practiced precisely what he preached and lived a blood-soaked life, killing his enemies right and left, in Medina (expelling all the Jews along the way), Mecca, and in the larger conquests through the Arabian peninsula up to the end of his life.

Which brings us to jihad. This struggle against unbelief is fundamental to the message of the Quran (indeed, one wonders about some influence from Zoroastrianism, with its relentless black-white outlook) and one question is whether it is formulated in military terms in the text itself, or only in the ancillary Hadith. There are many sections about war, usually focused historically on the early battles of Muhammed which are plainly life or death struggles for the faith. War is definitely the answer, and the pagans are reviled and attacked in the most absolute terms. God expresses himself through the success of his believers in arms.

But the Quran also claims to be a very general text, being the last and final revelation, so its lessons are not simply confined to their historical moment, but apply to all the faithful still today. This makes for a messy theology. The practice of going out hunting for unbelievers to forcibly convert is not explicitly promoted, as far as I could read, despite all the hatred directed at them. Indeed, Muslims are instructed to live in community with each other and to leave areas where they are a minority (i.e. Mecca during the exile in Medina). At the same time, the struggle against unbelief is to be unremitting, so the more explicit directive to military jihad that one finds in the Hadith is very consonant with the Quran in this respect. And of course the historical record of Muhammed's career and the ensuing centuries, when Muslim armies swept the known world, makes the point more eloquently still. Overall, it supports the idea that jihad is properly understood in the original sense, to be a military conquest of unbelievers until the whole world takes up the one true faith.

Be not weary and
Faint-hearted, crying for peace,
When ye should be
Uppermost: for God is
With you, and will never
Put you at a loss
For your (good) deeds.
 (47:35)

The Quran, for instance, promotes terrorization of unbelievers, as though the theology of hell were not already disquieting enough. It also allows polygamy, which, in my opinion, leads inexorably, if indirectly, to war by the excess males of a society. Females captured on battle were, and, if one is to believe reports about ISIS, remain, fair game to jihadists. In Muhammed's day, one can put a somewhat more generous construction on this policy, as a way to provide for widows in a violent, militaristic age. But then his marriage to Aisha (one of his thirteen wives) suggests something quite different ... a Koreshean zeal for a more youthful additional wife.

If ye fear that ye shall not
Be able to deal justly
With the orphans,
Marry women of your choice,
Two, or three, or four;
But if you fear that ye shall not
Be able to deal justly (with them),
Then only one, or (a captive)
That your right hands possess.
That will be more suitable,
To prevent you
From doing injustice.
 (4:3)

Incidentally, married life was not without its problems. In one chapter, he complains about wifely insubordination and threatens to divorce them all:

It may be if he [Muhammed]
Divorced you (all),
That God will give him
In exchange Consorts
Better than you,-
Who submit (their wills),
Who believe, who are devout,
Who turn to God in repentence,
Who worship in (humility),
Who travel (for Fiath) and fast,-
Previously married or virgins.
 (66:5)

But back to the main theme of what to do about unbelievers:

Therefore, when ye meet
The Unbelievers (in fight),
Smite at their necks;
At length, when ye have subdued them,
Bind a bond
Firmly (on them); thereafter
(Is the time for) either
Generosity or ransom:
Until the war lays down
Its burdens. Thus (are ye
Commanded): but if it
had been God's Will,
He could certainly have exacted
Retribution from them (Himself);
But (He lets you fight)
In order to test you,
Some with others.
But those who are slain
In the way of God,-
He will never let
Their deeds be lost.
 (47:4)

There are various mercies and controls put on war against unbelievers, such as the acceptance of conversion on its face, and the directive to not be vindictive in victory, and to attack only in defense, not in offense. But the plastic nature of victimization narratives is such that, as we observe all over world, groups can always construct some way in which they are under attack and thus justify attack. Christians in the US moan constantly how victimized they are by those arrogant atheists, etc. Indeed the insufferable arrogance of the unbelievers is a constant (and rather ironic) theme in the Quran.

Your God is One God:
As to those who believe not
In the Hereafter, their hearts
Refuse to know, and they are arrogant. 

Undoubtedly God doth know
What they conceal,
And what they reveal;
Verily He loveth not the arrogant. 

When it is said to them,
"What is it that your Lord
Has revealed?" they say,
"Tales of the ancients!" 

Let them bear, on the Day
Of Judgement, their own burdens
In full, and also (something)
Of the burdens of those
Without Knowledge, whom they
Misled. Alas, how grievous
The burdens they will bear!
 (41:22-25)

The Quran is an interesting blend of Jewish and Christian theology (Mostly Jewish, however, which accords with Muhammed's principal influences). Muhammed comes off as something of a Paul-like character, reshaping the somewhat foreign theology of Judaism for a new audience, language, and age with forceful, confident, and ceaseless proselytizing. The schizophrenic, two-faced nature of god is extreme, as he is called terrible, awful, and judgemental in the same breath as he is the most merciful. Clearly the audience for this message was intensely tribal, and the transposition of the old family & tent tribalism into a new religious tribalism of believer vs unbeliever was as historically momentous as it was psychologically astute and intellectually vacuous. In our own day, it continues to be the nail upon which multitudes of Muslims, disaffected as they routinely are by their own defective systems of civil society and government, hang their hopes and hatreds.

But there was one enormous oversight in all of Muhammed's hundreds of pages of detailed directives and repetitive trash talk, which was the matter of succession. Muhammed never revealed the identity of, or method of choosing, the next leader, let alone all the successive leaders of the community. This despite the huge significance he placed on the community, its coherence, and its leadership. This failure has haunted Islam from the day of his death, when the wrangles and ultimately civil wars over Ali, Abu Bakr, and Shiism began. The founders of the United States, in contrast, stand head and shoulders over Muhammed in that they authored a durable mechanism of peaceful succession and of government in general. A beneficent god could surely have managed as much for Muslims.

"The Kharijites argued a true believer would have trusted his fate not to diplomacy but to ongoing warfare and God will decide." .. from a Western commentary.

Unfortunately, Islam has vacillated between legitimacy by blood and legitimacy by battle, per the most ancient template. It is incidentally odd that the theocratic model we find in Iran has been so rarely employed, in light of Muhammed's example. In any case, this continues to be a glaring weakness of the Muslim world and especially of ISIS, Al Qaeda, Taliban, and other fringe groups that send up fatwas and set up caliphates that get nothing but scorn from mainstream Muslims (unless they succeed ... nothing succeeds like success!). The charisma of the moment, yoked to fanaticism, fundamentalism, and terror, may be able to scatter a dysfunctional and totally corrupt government as found in Iraq or Syria, but its staying power against well-functioning, legitimate, (not to mention open, truth-seeking, and democratic) societies is going to be extremely modest.

They will recline on Carpets,
Whose rich inner linings
Will be of rich brocade: the Fruit
Of the Gardens will be
Near (and easy of reach). 

Then which of the favors
Of your lord will ye deny? 

In them will be (Maidens),
Chaste, restraining their glances,
Whom no man or Jinn
Before them has touched; 

Then which of the favors
Of your Lord will ye deny?
 (55:54-57)

In the end, we have to ask how much Islam per se is responsible for the features of the Muslim world that keeps it in the news on such a regular basis. Many argue that religion has no significant effect, for it can and is interpreted quite flexibly depending on the material circumstances of the society. We would have to look to our own actions from the Crusades, colonialism, and recent US foreign policy to locate the reasons why some Muslims are so bitter about modernity and ready to take up arms anywhere they can fight infidels or set up fly-by-night caliphates.

Obviously, there is some truth to that view. The spectrum of Islamic interpretation is vast, from the Sufis to the Salafists. The Quran supports numerous views, and offers some compassion in amongst the rest. But I think that ideology is also critically important. We do not absolve the Nazis by accusing the Versailles treaty of driving Germans to  world war and genocide. Ideology drives world affairs, as the narrative force that shapes our responses to material conditions. No ideology, no Inquisition, no cold war, no racism in the US, no Crusades, no "holy land", no patriarchy, etc. ad infinitum. As the Quran exemplifies, people will find ideologies to suit them, (or have them forced down their throats), but if those ideologies claim to be rational, yet are not rational, the seeds of their own critique, if not destruction, can be sown. At least one can hope.

Fighting is prescribed
For you, and ye dislike it.
But it is possible
That ye dislike a thing
Which is good for you,
and that ye love a thing
Which is bad for you.
But God knoweth
And ye know not.
 (2:216)

For instance, one of the momentous issues in Islamic ideology is its stance towards the modern world. Which is not easily compatible with traditional Islam. Globalism breaks down cultural borders, infecting everyone with consumerism, liberal political philosophies, women's liberation, and religious skepticism. The commerce and especially the oil-addiction of modernity has made some Muslim nations unimaginably wealthy, while more generally, the advent of colonialism, interacting with the technological and intellectual power of the West, has put Islamic culture in a poor, embattled, even subservient, position. The Egyptian philosopher Qutb came to a shocked and fundamentalist conclusion- that modernity is the mortal enemy of Islam. Quran and Sharia must be the sole answer to all of mankind's problems.

"The concept of the imperceptible is a decisive factor in distinguishing man from animal. Materialist thinking, ancient as well as modern, has tended to drag man back to an irrational existence, with no room for the spiritual, where everything is determined by sensory means alone. What is peddled as 'progressive thought' is no more than dismal regression."

Let not the Unbelievers
Think that they can
Get the better (of the godly):
They will never frustrate (them). 

Against them make ready
Your strength to the utmost
Of your power, including
Steeds of war, to strike terror
Into (the hearts of) the enemies,
Of God and your enemies,
And others besides, whom
Ye may not know, but whom
God doth know. Whatever
Ye shall spend on the Cause
Of God, shall be repaid
Unto you, and ye shall not
Be treated  unjustly.
 (8:59-60)

The Saudi rulers in particular have blended this ideology with their wealth and Wahhabist religious structure into a globe-straddling ideological machinery of fundamentalist madrassas that groom the cannon fodder of jihad. Yet Attaturk, a generation before, came to the opposite conclusion, frog-marching Turkey into a quasi-secular, modernizing state. What is it to be? A great deal depends on the fairness and decency the rest of the world can bring to the table. But more depends on the readings that Muslims give themselves of their central text, history and traditions. The war for the ideological / theological soul of the Muslim world is highly consequential. And the core text is not, on the face of it, particularly helpful towards a tolerant, cosmopolitan, and peaceful reading.

It may be that God
Will grant love (and friendship)
Between you and those whom
Ye (now) hold as enemies.
For God has power
(Over all things); And God is
Oft-Forgiving, Most Merciful. 

God forbids you not,
With regard to those who Fight you not for (your) Faith
Nor drive you out
Of your homes,
From dealing kindly and justly
With them: For God loveth
Those who are just.
 (60:7-8)

• An Islamic theologian on the value of theology and the fundamentalist turn. "Islamic theology is based on an ethical rather than speculative imperative. Many Qur’anic verses and hadiths show that iman or “true faith” is obligatory and rewarded by paradise, and that kufr or “unbelief” is wrong and punished by hell." This shows, unsurprisingly, that a search for truth is not really part of the program.
• An advanced discussion of ISIS and the Muslim world, on POI.
• Shiite cleric sentenced to crucifixion in Saudi Arabia.
• Christianity ... can be taken several ways as well.
• Maher on Islam. And more, more, more, more, more.
• What do regular Muslims think?
• Is the Quran an example of "derp"?
• And now some very peaceful news, from Indonesia.
• The unending irony that is Pakistan: "An anonymous senior Pakistani security official stated: 'It is a worrying development that the TTP is regrouping close to the border right under the nose of the Afghan security forces.'"
• Wesley Clark on policy: "We just can’t believe that we were responsible for creating it. We weren’t. The money that went into ISIS came from Saudi Arabia and Qatar, and it came particularly from the work of the Saudi leadership trying to find an opposition to Bashar Assad in Syria."
• Fear is a political act, and a media goldmine.
• Gosh- what happened to the middle class?
• GOP heads to new lows. Suppression or outreach, that is the question.
• What is the nature of our current form of capitalism? And of our political economy?
• And what's the problem with Europe? "The Eurozone’s current problem arises because one country - Germany - allowed nominal wage growth well below the Eurozone average, which undercut everyone else.... Within a currency union, this is a beggar my neighbour policy."
• Krugman on Japan- now is no time for false fiscal responsibility.
• Notes and data on inequality.
• The Fed can set long as well as short rates.
• Economic graph of the week. Our economic prospects continue to decline.

Regulatory Dynamism in Evolution

While the proteins stay mostly the same, the management evolves much faster.

When looking at evolution in the genetic code, we tend to focus on the most conserved elements which can take us the farthest back in time. Essential proteins like metabolic enzymes that we recognizably share with bacteria, or the translational apparatus of ribosomal RNA and related proteins, shared in all life forms. But to look at more rapid and recent evolutionary processes, one has to look at other parts of the genome which churn a lot faster and can be, incidentally, far more difficult to discern.

General illustration of regulation of gene transcription; DNA is the black/green line, the yellow lozenges are histones, and protein regulator binding sites are red. Various regulators bind near and far upstream of the gene, (whose start site of transcription is shown by the arrow, bottom right), all conspiring to promote or retard formation, placement, and activation of the initiation complex of proteins (blue) that includes the RNA polymerase.

The DNA sites that direct transcription tend to be such fast-changing genetic elements. They are short, often redundant, degenerate (able to accommodate various errors) and modular, meaning that they can occur in various positions and orientations with respect to their target gene and still work. Their shortness means that they can be born by mutational accident, and also that they are hard to recognize by text-comparison methods.

Human-mouse comparison of three protein regulators, (GATA, MAX, cMyc), and a brief stretch of DNA they bind to (red and blue). The blue MAX site in the middle was born in the primate lineage, while the others are recognizably conserved. From the top, the general coordinates of the genomic region, over this gene, EPB41, which encodes a protein that provides special flexibility to erythrocyte blood cells. Then various annotated features (colored bars) looking for regulator binding sites, then graphs of the physical binding data for each regulator (colored graphs).

They are also enormously important for evolution and biology in general. There are many hundreds of gene regulating proteins encoded by the genome, each of which bind to some DNA site, typically 6 to 16 base pairs long. These protein+site complexes constitute the first line of gene regulation, and, though virtually every possible aspect of biology can be bent to regulatory uses, typically the most sensitive and influential mechanism of gene regulation.

"... there are an estimated ~1700–1900 TFs [transcription factors, or regulators] in the human genome."

A recent paper discussed a new-ish method to study the phylogeny of such sites. The first step is to use a modern technology to find such sites, physically purifying such individual regulatory proteins while they are still bound to DNA in a cell, and later sequencing the underlying DNA snippets. This allows, for a single regulatory protein, all its target sites in a genome to be mapped (at least the sites being used under the condition used to grow the cells for the experiment, in this case erythroblast cell lines). The researchers did this (or actually got data from others) for several different transcriptional regulators in human and mouse cells.

 Then they used sequence comparison methods to deduce the history of these sites in the lengthy time of divergence between the two lineages, over the sequenced genomes of baboon, chimpanzee, rat, squirrel, tarsier, and other species. They used not only sequence conservation of the sites, but larger-scale studies of how the genomes relate to each other, called synteny analysis. This depends on large regions of diverged genomes being, at least on a patchwork basis, descended from each other, even if some of the sequences they contain are not so recognizable. Over time, various accidents in recombination and replication cause genomes to slowly re-arrange relative to their ancestors.

Synteny comparisons of human and chimpanzee (top) and human and mouse (bottom). The colors from one genome's chromosomes are projected / sprinkled as they correspond to the other genome. The Y chromosome tends to have a lot of junk or unrecognizable sequence.

The finding of this paper that is of general interest is: "Notably, between ~58–79% of all human TFBSs [transcription factor binding sites] had inferred origins after the human-mouse split." This is far more rapid change than one would see in encoded proteins, of which about 80% are recognizably shared between mice and humans. It follows that the regulation system, which controls where, when, and how much genes are expressed, is far more variable through evolution, than are the products of those genes. This makes sense when we see the slight variations over human populations and among closely related species that tend to concern relative sizes of bodies and parts, slightly more or less some some feature, coloration, etc. It fits very well with the typically gradualist nature of evolution, operating on thousands of genes and hundreds of thousands, if not millions, of their regulatory sites all in parallel over populations and time.

"For all six factors analyzed, the majority of human TFBSs [transcription factor bound sites] bound in vivo were originally absent in human-mouse common ancestor, which is consistent with previous cross-species comparisons noting substantial divergence in ChIP-seq protein-binding events across the two species and similar comparisons presented here, and is also comparable to detailed analyses conducted in Drosophila using alternative approaches" 

"Genes located nearest to hominid-specific binding sites were more frequently enriched for neural and sensory-related functions, and were in many cases involved in neurological pathways (Table S2). CTCF, MYC, and SOX2 target gene sets were all enriched for GO categories involved in sensory perception, while GATA1, MYC, ETS1, and MAX were enriched for neural development and differentiation categories."

• Terrorists win ... in the US.
• And in Afghanistan.
• Annals of feudalism: the no-compete "agreement".
• A jobs shortage, not a skills shortage.
• The next financial crisis may come sooner than we think, at least to poor people.
• In praise of helicopter money.
• The shame of "rocket scientists" who work in finance / fraud.
• This week in WSJ: "... the Obama economy ..." The definition of chutzpa and hypocrisy is to cause an economic catastrophe, then do everything in one's ability to stifle effective action against it, then blame the other party for the result.

Thought Experiments in an Equal Pay World

Imagine ... what if everyone could get a job, and every job paid exactly the same? 

The labor market is highly problematic. It doesn't value people or work fairly, rewards destructive behavior (pollution, lawyering, lobbying, finance), and fails to reward socially constructive work (teaching, nursing, mothering, cleaning, farming). It tends to reinforce social hierarchies that have roots in patriarchy and class, perpetuating patterns that have questionable social value. Salary decisions are typically quite distant from business considerations, as CEOs have amply demonstrated, (both on their own behalf and over their minimum wage minions), depending more on the social and power relations of the parties involved.

There are also the persistent issues of gender and race inequality in hiring and pay- conditions that were supposed to have been solved by now, but which rear their heads again and again because of biases in the social system, if not in humanity itself. There is also the appallingly low pay provided by some of our biggest companies and industries (Walmart and farm labor come to mind) that rely on taxpayers to keep their shoddily paid employees fed, clothed, and housed. One way to solve all these problems would be to stipulate that all jobs pay the same wage. That average pay is currently about $44,322 per year, full time, in the US.

And if one is interested in addressing economic and social inequality in a comprehensive way, all the (progressive) solutions on the taxation side are trying to capture a horse after it has left the barn. The power that employers have now to pay rock-bottom wages to workers while paying themselves like kings means that they will likely have the means to make up for any tax increases. One solution is to insure that the labor market favors workers consistently, making jobs available to all, and using plenty of fiscal spending in times of slack private investment. But that simply works within the system, a system that is run, via our political and financial elites, by the incumbent powers of class and wealth, from which labor friendly policy is as likely to come as pennies from heaven.

Let's start with some easy issues first. How would currently high-paying professions be staffed if they were not paid differentially? Such work as financial engineering, dentistry, or medicine. Or CEO, lobbyist, sports star, political consultant, movie actor? The current system is, frankly, obscene in this regard. Would NBA teams not be able to field players if they did not paid them like kings? Probably, and one might get players who actually want to play, and they would be selected just as stringently, because the ancillary benefits of fame, status, and pleasure would remain, and the limited number of teams (and audiences) would remain likewise. More obscure fields like oil drilling, sales and marketing, dental hygienist, etc. might be more difficult to fill. But are they really paid that well? Typically not. It would probably just take some modest interest and training to attract people who otherwise might end up as farm workers or janitors, with less pleasant work conditions.

Similarly, the challenge and personal rewards of professions like medicine would remain and attract perhaps an even better class of trainees than they do now. Professions such as finance whose mind-numbing and pointless nature is now relieved only by their high pay might indeed contract, and frankly that would be a very good thing. So we would enter a world where students study what they are interested in, and enter professions that suit them, which select them on every basis of training and qualification as now, but without the lure of unusual monetary reward or penalty.

How about the low-wage work on which so much of the economy depends? Firstly, easily half of this work is completely useless. Unlivable wages allow many employers to hire far more people than needed, (fast food, retail; imagine being a walmart greeter), flood markets with low-margin franchises, and avoid efficiencies and mechanization. Labor shortages commonly spur efficiency gains. Secondly, a great deal of effort otherwise spent fighting against and dealing with unions might be saved by an equal pay regime. But in the end, paying people decently should come ahead of the consumer's ability to command the cheapest goods and services.

Entrepreneurialism is a somewhat more ticklish problem. How should we encourage business formation, innovation, family businesses, investment, and all the other energies of the free enterprise system if greed is no longer the central motivator? I think a general answer to that is to separate corporate and personal income on a stringent basis. If one wants to start a company that does great things, fine. One can grow it to globe-straddling size, but one can not pay oneself more than any other employee. That goes for bonuses, shares, etc.. all the remuneration that is now fair game would be strictly controlled, via the tax reporting system, and perhaps other enforcement, to one simple salary.

This relates to the problem of how investment would take place. Personal savings from such a system would probably be modest, and insufficient for the capital needs of the economy. People would generally be more dependent on (and willing to pay for) government programs to manage life-cycle savings, catastrophic contingencies, education, etc. I think one way to deal with the investment issue would be to allow special corporations (one might even call them "banks"!) and corporate entities like non-profits and educational institutions to have investment holding roles. Thus there would be a large ecosystem of investors and investments that do not significantly touch /affect personal income, but run large-scale investments in private enterprises due to the good judgement and personal values of the people involved. If the managers were unsuccessful, they might be demoted from their C-suites to street sweeping, but their personal income & sustenance would not be affected. One's social standing (and values) would be a much stronger aspect of motivation than greed, as would the personal satisfactions of the work one does. This would perhaps hearken back to the conditions in Antiquity, (occasionally, at least), when leading people and families competed to contribute to the state, not to leach from it, due to an intense sense of honor and reputation.

How about parenting? A fair system would pay for child care, whether done by parents or outside caregivers. So perhaps a parent could be paid through the first five years of a child's life if the parent decided to stay home, ideally at a full salary. This would make the decision to work or stay home shaped by personal preferences, such as career goals, rather than about finances. The same would go for care-giving to elderly parents and relatives, subject to some kind of certification that it is a full time occupation.

Perhaps the most difficult aspect of such a system is the impetus towards a black market, to under-the-table payments, gold-plated executive suites that pay in helicopter rides, escort services, etc. In our political system, with all the principles and deterrents against corruption, corruption remains rampant, indeed functionally legalized. Similar pressures would be inevitable in a tightly controlled equal pay system. Communist systems routinely elevated powerful people into great effective wealth, whatever their nominal salary. The best I could propose is again a strict separation between corporate and personal books, with transparency and strict regulation of what goes where. The current system of business tax deductibility, for example, requires extensive itemization and reporting, all to create an appalling drain on the public coffers, for the benefit of those need no such benefit. In the end, we organize society to limit some freedoms, (killing, fraud, theft), so that other and better freedoms may flourish. And perhaps the freedom to pauperize / feudalize your fellow citizens might not be as valuable as the freedom to have a decent and equitable life.

And how would this universal pay be set? It would be a broad economic policy exercise that fits closely with MMT (macro)economics. The tuning could be quite simple- if inflation threatened, pay would not be raised, while recession or deflation would be easily solved by raising the standard salary. Ultimately, its level and its value would be set by overall GDP and productivity, but the government, as the creator (and destroyer) of the currency, could easily make more or less of it and spend it in the form of salaries or other projects to fine-tune through any economic variation. Variations that, naturally, would be rare if not unheard of in this proposed society.

It is a thought experiment to imagine a system less besotted by greed, class, and injustice, more valuing of human e-qualities. One has to doubt its feasibility, but I believe it is a relevant ideal, or perhaps counter-ideal, for our time.

• Worship of money and those with it, cont.
• The middle class is kaput.. how did this happen in a democracy?
• Gates on Piketty. 
• "One side insists that the only important question is whether the truth-claims of religion are actually true; the other side says that question doesn’t even matter, and then wonders what “truth” is, anyway. It’s the overly literal-minded versus the hopelessly vague."
• More on austerity.
• Could we bring extinct animals back? But without habitat or stable climate, what would be the point?
• Reality, as usual, has a liberal bias.
• Meltdown in Iraq- the final chapter of Bushistic incompetence.
• Bolivia- a happy case study of good governance and fiscal policy ... and throwing out the IMF.
• On the impunity of finance.
• Annals of feudalism ... Conoco bullies its employees.
• The US deficit is low ... too low, as deflationary concerns drive the markets, and especially the specter of Europe melting down.
• Sleep is really, really good for your brain.
• Death might not quite as bad as imagined, either.
• Insanity and religion ... not always either / or.
• ISIS propaganda image of the week. Move along ... nothing Freudian here.

Organizer Without a Brain: the Centrosome

The microtubule organizing center of eukaryotic cells, which guides mitosis and nucleates cilia.

One of the more immediate wonders of biology is the division of cells and the organized march of chromsomes that accompanies it, girdled by a beautiful web of microtubules. These microtubules all emanate from something called the microtubule organizing center (MTOC), or centrosome, which is itself strictly duplicated during cell division. It all looks so alive. Yet the process is one of molecules each doing their little thing in blind fashion to make a greater and very dynamic whole.

In this image of a large eukaryotic cell, DNA is stained blue, microtubules are stained green, and the centrosome is stained red / orange. At some point during the mitotic process, the kinetochores (possibly the pink/lavender spots) would line up strictly along the midline between the two centrosomes.

Centrosomes are special to eukaryotes- there is no trace of them in bacteria. They also have no DNA or other sign of being descended from some symbiotic or other bacterial forebear, unlike the mitochondrion or chloroplast, perhaps even the peroxisome. (Though some researchers find they contain a few special RNAs and argue for an endosymbiotic origin on that basis.) Yet they are quite complex organelles, based on the same tubulin that composes the microtubules of the cell generally, but with hundreds of other proteins added in. They organize not only the microtubule asters that drive mitosis, but also form the basal bodies of cilia- the flaggella of eukaryotic cells, again composed of microtubules. These cilia in turn have important, though only recently-discovered roles in mechanisensory and chemical signaling.

The centrosome and its component centrioles. The micrograph cross section shows parts of each centriole from one centrosome.

The centrosome is composed of two centrioles, one of which is the mother, and the other the daugher. At each cell cycle, they split apart and each grows another daughter centriole to reconstitute a full centrosome. Each centriole resembles a microtubule, which is a tube of nine paired tubulin tubules, but has an extra set of tubules, so nine triple tubules of tubulin. At the base of each centriole is something called a "cartwheel", which is made up mostly of a non-tubulin protein (Sas6) that forms a nine-fold symmetric ring that nucleates growth of the centriole, which in turn nucleates growth of the microtubule.

Detailed structure of microtubules (top) and the centriole (bottom). Note the two pairs of tubules in the microtubule, but triplets in the centriole, or basal body. The third tubule appears to template or make space for the dynein arms, which are the motors that allow cilia, for instance, to wave and move.

Models of the molecular structure of the "Cartwheel" protein complex, which  (d) templates and nucleates the centriole structure. Microtubules (purple) fit to the outside spokes of the cartwheel (blue). In the electron micrograph (e), three cartwheel stacks can be seen at the bottom, at the base of the centriole, and higher up, with lower electron density, the microtubule.

"Studies using human cells have revealed a mechanism that regulates cartwheel assembly through controlling the amount of SAS-6 in the cell. SAS-6 starts to accumulate at the end of the G1 phase and decreases in anaphase through proteasomal degradation mediated by APC/CCdh1 [19]. When the SAS-6 level is artificially increased by overexpression of non-degradable SAS-6, excess procentrioles are formed on the mother centriole."

Another electron micrograph of the centrosomes and their microtubule junctions.

The main component of all these structures is tubulin, the building block of all microtubules, which, along with actin, make up the cellular cytoskeleton of eukaryotes. Actin is smaller and free to form more flexible structures, (as well as being used to form the structural scaffold of muscle action), while microtubules make bigger structures (in cellular terms) like that which spans the whole cell for division, making cilia / flagella, and conducting cargoes along the enormous distances of nerve cell axons. Not all eukaryotes have centrosomes, (notably plants and yeast don't), but all have some form of microtubule nucleating center, (MTOC), of sometimes more modest construction. While microtubules are made of alpha and beta tubulin, the centrioles have a third form, gamma tubulin, which only exists at the nucleating base, not in the bulk structure.

Diagram of nucleation from a cartwheel (red) to a centriole (blue).

Unfortunately, less is known about how all this works dynamically than about its structural components. A recent paper covered two key proteins (Cnn and DSpd-2, in fruit flies) that seem to be all that are required to turn a bare centriole into a busy MTOC with hundreds of other proteins in a nimbus around it (the pericentriolar material). These key proteins are controlled by phosphorylation which is a common element of the cell cycle, and when turned on, come into the most interior precincts of the centrosome/centriole, and then migrate slowly outwards, with new molecules arriving at the center as long as the cell is in the requisite state.

"Mimicking phosphorylation allows the PReM domain [part of Cnn] to multimerize in vitro and Cnn to spontaneously assemble into cytosolic scaffolds in vivo that can organize MTs. Conversely, ablating phosphorylation does not interfere with Cnn recruitment to centrioles, but inhibits Cnn scaffold assembly. We speculate that, like Cnn, DSpd-2 can assemble into a scaffold and that this assembly is regulated in vivo so that it only occurs around mother centrioles."

At the other end, a good deal more is known about how microtubules attach to the kinetochores (structures at the center of chromosomes -at DNA centromeres- that anchor them to the mitotic spindle). This is not really in the scope of the post, but again, phosphorylation of key proteins is the theme, as is regulated assembly and disassembly of the microtubule itself. Disassembly right where it abuts the kinetochore causes shortening, thus tightening of the whole spindle, as long as the kinetochore has properly captured microtubules on/from both sides, i.e. both centrosomes, which is another complicated and phosphorylation-regulated process.

Example of a model for microtubule dynamics during one part of mitosis, with microtubules in purple,  (and unconnected microtubules in yellow, cell edge in gray), the centrosome in pink dots, and relevant motor proteins in green and salmon. The point is that, if relevant motors and attachment functions are regulated and happen at the right times, the system can accomplish complex tasks.

It is worthwhile to note that while the replication of the centrosome and its component centrioles is strictly regulated with the cell cycle, the same core system is used to create the basal bodies of cilia, and can create organizing centers from scratch. It does not require a pre-existing centrosome (unlike mitochondria, chloroplasts, and cells, which always come from pre-existing respective cells or cell-ish organelles). Sometimes, the basal body is the same as the centrosome; when cell division is done it migrates to the membrane. But many cells have multiple cilia, and each one has a newly created basal body at its base, whipped up without the complicated replication process. So it appears that replication is more a regulated restriction of MTOC creation than it is a necessary precondition of MTOC birth.

The science of the microtubule nucleation systems is still underway, but the direction is clear, as in any other area of molecular biology that has been laid bare to date. Molecules of some complexity, equipped with various means of regulation, such as regulated transcription and synthesis, outright destruction, interaction with various partners, or covalent modification like phosphorylation, neddylation, methylation, palmitoylation, GPI-anchoring, etc., can find their places and times of action in chemically explicable ways within a cell that is a vast, if microscopic, machine.

• A relevant review of centrosomes, and a second, and a third.
• Motors on the microtubules.
• Freedom & security flows from law, not from the barrel of a gun.
• But paranoia is patriotism and apple pie.
• Economics can say a few things about recent events.
• To save Lehman or not?
• Poor, poor, AIG.
• Quackonomic vocabulary.
• Inequality and the freezing of upward mobility, in Venice.
• Government by the corrupt, for the corrupt.
• Startups not all they are cracked up to be.
• The European economy is disastrous across the board.
• Krugman on the crisis.
• Requiem for the incandescent light bulb, though for its corrupt business practices, who knows?