#65. Why There is Sex [evolution, genetics]

EV  GE

Red, theory; black, fact

The flower Coronilla varia L.

Sex as an evolvability adaptation

There are always two games in town: reproduction and evolution. Since we live on an unstable planet where the environment can change capriciously, species here have been selected for rapid evolvability per se to enable them to adapt to the occasional rapid environment changes and not go extinct. Apparently, mutations, the starting point for evolutionary adaptation, become more common when the organism is stressed, and stress may partly be a forecast of loss of fertility due to a developing genome-environment mismatch. Bacteria exhibit the large mutation of transformation under stress conditions, and three types of stress all increased the meiotic recombination rate of fruit flies (Stress-induced recombination and the mechanism of evolvability. Zhong W, Priest NK. Behavioral ecology and sociobiology. 2011;65:493-502). Recombination can involve unequal crossing-over in which changes in gene dose can occur due to gene duplication or deletion. However, since most mutations are deleterious (there are more ways to do something wrong than to do it better) many mutations will also reduce fertility, and at precisely the wrong moment: when a reduction in fertility is impending due to environment change. The answer was to split the population into two halves: the reproduction specialists and the selection specialists, and remix their respective genomes at each generation.

The roles of the two sexes

Females obviously do the heavy lifting of reproduction, and males seem to be the gene testers. So if a guy gets a bad gene, so long, and the luckier guy next to him then gets two wives. The phenomenon of greater male variability (Greater male than female variability in regional brain structure across the lifespan. Wierenga LM, Doucet GE, Dima D, Agartz I, Aghajani M, Akudjedu TN, Albajes‐Eizagirre A, Alnæs D, Alpert KI, Andreassen OA, Anticevic A. Karolinska Schizophrenia Project (KaSP) Consortium. Hum. Brain Mapp., doi:10.1002/hbm.25204, and I have never seen so many authors on a paper: 160.) suggests that mutations have more penetrance in males, as befits the male role of cannon fodder/selectees. What the male brings to the marriage bed, then, is field-tested genetic information. This system allows many mutations to be field tested with minimal loss of whole-population fertility, because it is the females who are the limiting factor in population fertility.

Chromosomal mechanisms of greater male variability

Chromosomal diploidy may be a system for sheltering females from mutations, assuming that the default process is for the phenotype that develops to be the average of the phenotypes individually specified by the paternal and maternal chromosome sets. Averaging tends to mute the extremes. The males, however, may set up a winner-take-all competition between homologous chromosomes early in development, with inactivation of one of them chosen at random. The molecular machinery for this may be similar to that of random x-inactivation in females. The result will be greater penetrance of mutations through to the phenotype and thus greater male variability. 

Quantitative prediction

This reasoning predicts that on a given trait, male variability (as standard deviation) will be 41% greater than the female variability, a testable prediction. 41% = [SQRT(2) -1] × 100. Already in my reading I have found a figure of 30%, which is suggestive. 

Mechanistic reconciliation with Mendel's laws

The postulated chromosome inactivation process may feature an exemption mechanism that operates on genes present in only one copy per parent. The effect will be to double the penetrance of dominant alleles at that gene. 

#38. Can Irreducible Complexity Evolve? [genetics, evolution]

EV   GE

Red, theory; black, fact

2 x 2

The Key Insight

Sexual reproduction may allow the evolution of irreducible complexity by increasing the intrinsic complexity of the basic building block of change, the mutation.

Irreducible Complexity 

Influential biologist Richard Dawkins wrote in "The God Delusion" that a genuine case of irreducible complexity will never be found in biology. A case of irreducible complexity would be some adaptation that would require an intelligent designer because it could never evolve one mutation at a time, and Dawkins believes there is no such intelligent designer in biology.

In classic natural selection, each mutation must be individually beneficial to its possessor in order for selection to increase its prevalence in the population to the point where the next incremental, one-mutation improvement becomes statistically possible. In this way, all manner of wondrous things are supposed to evolve bit by tiny bit. You have irreducible complexity if an advantageous evolutionary innovation requires two mutations,  but neither confers any advantage in isolation and so cannot be selected up to a sufficiently high frequency that the second mutation is likely to happen in the background of the first.

However, I am seeing irreducible complexity everywhere these days. 

Possible Cases of Irreducible Complexity

For example, your upper-jaw dentition must mesh accurately with that of your lower jaw or you can't eat. Thus, the process of evolutionary foreshortening of the muzzle of the great apes to the flat human face could never have happened, assuming that a single mutation affects only the upper or lower jaw. 

Furthermore, how can any biological signaling system evolve one mutation at a time? At a minimum, you always need both the transmitter adaptation and the receiver adaptation, not to mention further mutations to connect the receiver circuit to something useful.

The evolution of altruism presents a similar problem. The lonely first altruist in the population is always at a disadvantage in competition with the more selfish non-mutants unless it also has a signaling system that lets it recognize fellow altruists (initially, close relatives) and a further mutation that places the altruistic behavior under the control of the receiver part of this system. Thus, altruists would only be altruistic to their own kind, the requirement for altruism to be selected in the presence of selfishness. Finally, the various parts of this system must be indissolubly linked in a way that the non-altruists cannot fake.

A Solution   

Consider the crossing-over events that occur during meiosis as complex mutations: two changes to the genome from a single event, each corresponding to one end of the DNA segment that translocates. In crossing over, two homologous chromosomes pair up along their length and swap a long segment of DNA, a process requiring two double-chain breaks on each end, and their corresponding repairs. A very far-reaching change to the genetic information can occur during crossing-over that is termed unequal crossing-over. This form of the process arises because of inaccuracies, sometimes major, in the initial alignment of the homologous chromosomes prior to crossing-over. When the process is finished, one chromosome has been shortened and the other has been lengthened. This is the major source of gene duplication, which, in turn, is a major source of junk DNA, the part that is classified as broken genes.

A Mechanism for the Evolution of Complexity 

Anatomical features such as jaw length and axon targets may be controlled by variations in gene dose that originate in unequal crossing-over.

In this way, a concerted change affecting multiple distinct sites becomes possible. The two ends of the recombinant segment can in principle be functionally unrelated initially. They become related if both are affected by the same complex mutation and the entire change increases fitness and is thus selected.

A single complex mutation could in principle produce a communication channel at one stroke because of the number of simultaneous changes involved. 

Statistical Issues

The probability of a combination of simultaneous local changes being beneficial to the organism is much smaller on mathematical grounds than is the probability of a given single-nucleotide change being beneficial. However, these unfavourable statistics are at least partly offset by the existence of a dedicated system for producing complex mutations in large numbers, namely meiosis, part of the process of maturation of egg and sperm cells.

The Big Picture 

Complex mutations provide a way for a species to discontinuously jump into new niches as they open up, possibly explaining how a capacity for this kind of mutation could spread and become characteristic of surviving species over time. This idea also provides another explanation for the lack of transitional forms in the fossil record.

#26. Why Organized Religion? Theory Two [evolutionary psychology]

EP

Red, theory; black, fact

Emotions are an "endophenotype," a term from functional magnetic resonance imaging, that provides a useful stepping stone from evolutionary arguments to explanations of our daily lives. 

Starting with the Emotion 

What is the mood or feel as you enter a place of worship and participate in the ceremonies conducted there? More than anything else, the mood is one of great reverence, as though one is in the presence of the world's most powerful king. Kings are supposed to "represent their race." 

Problem

If the emotional outline of people's behaviour is being partly randomized in each generation by recombination-type mutations, a consistent moral code seems impossible if we assume that morality comes mostly from peoples' inborn patterns of emotional reactivity, that is, the sum total of everyone's preferences. The purpose of a king may be to find and coincide with societies' moral center of gravity, around which a formal, if temporary, moral code can be constructed. In a complex society, everyone must be "on the same page" for efficient interaction. 

It Gets Bigger

The same problem no doubt recurs each time organisms come together to form a colony, or super-organism: the conflict between the need of a colony for coordination of colonists and the need of evolution for random variability. Such variability will inevitably affect the formulation and interpretation of the coordinating messages that the colonists exchange, like all their other inborn characteristics. 

A Social Solution 

With kingship comes the corrupting influence of personal power and  tyrannical government. Replacing a real king with a pretend-king named "God" would seem to be the solution that accounts for organized religion, but then one loses the flexibility that goes with having a flesh-and-blood king who can change his predecessor's laws based on current popular sentiment.

Mechanistic Interpretation 

However, human nature may well have a core-and-shell structure, with an "unchanging" core surrounded by a slowly changing shell. The former would be the species-specific objective function and produced by species-replacement group selection within the genus, and the latter would be due to selection of smaller units, and would represent the stratagems hit upon by our ancestors to meet the demands of the objective function in our time and place. This shell part may account for cultural differences between countries. The core may be implemented in the hypothalamus of the brain, whereas the shell may be implemented in the limbic system. The core, being very slow to change, could be managed by organized religion, whereas the shell could be codified by the more flexible institution of government. Though the core is unchanging overall, specific individuals will harbor variations in it due to point mutations, necessitating the standardizing role of religion. Synaptic plasticity would then be used to cancel the point-mutational variation in the objective function.

The Big Picture 

The core may consist of four pillars, or regulatory themes: regulation of genetic diversity, memetic diversity, altruism, and dispersal. Our energetic investment in obtaining each item is to be optimized.

#22. Proxy Natural Selection: The God-shaped Gap at the Heart of Biology [genetics, evolution]

EV   GE

Red, theory; black, fact

The Problem and My Solution 

Some entity must be responsible for compensating for the fact that our microbial, insect, and rodent competitors evolve much faster than we do because of their shorter generation times. In these pages, I have been variously calling this entity the intermind, the collective unconscious, the mover of the zeitgeist, and the real, investigable system that the word "God" points to. I here recant my former belief that epigenetic marks are likely to be the basis of an information storage system sufficient to support an independent evolution-like process. I will assume that the new system, "post-zygotic gamete selection" (PGS) is DNA-based.

Background 

First, a refresher on how standard natural selection works. DNA undergoes various mutations that add diversity to the genome. The developmental process translates the various genotypes into a somewhat diverse set of phenotypes. Existential selection then ensues from the interaction of these phenotypes with the environment, made chronically stringent by population pressure. Differential reproduction of phenotypes then occurs, leading to changes in gene frequencies in the population gene pool. Such changes are the essence of evolution.

My Solution, Big Picture 

PGS assumes that the genome contains special if-then rules, perhaps implemented as cis-control-element/structural gene partnerships, that collectively simulate the presence of an objective function that dictates the desiderata of survival and replaces or stands in for existential selection. A given objective function is species-specific but has a generic resemblance across the species of a genus. The genus-averaged objective function evolves by species-replacement group selection, and can thus theoretically produce altruism between individuals. The if-then rules instruct the wiring of the hypothalamus during development, which thereby comes to dictate the organism's likes and dislikes in a way leading to species survival as well as (usually) individual survival. Routinely, however, some specific individuals end up sacrificed for the benefit of the species.

The PGS Mechanism 

Crossing-over mutations during meiosis to produce sperm increase the diversity of the recombinotypes making up the sperm population. During subsequent fertilization and brain development, each recombinotype instructs a particular behavioral temperament, or idiosyncratotype. Temperament is assumed to be a set of if-then rules connecting certain experiences with the triggering of specific emotions. An emotion is a high-level, but in some ways stereotyped, motor command, the details of which are to be fleshed out during conscious planning before anything emerges as overt behavior. Each idiosyncratotype interacts with the environment and the result is proxy-evaluated by the hypothalamus to produce a proxy-fitness (p-fitness) measurement. The measurement is translated into blood-borne factors that travel from the brain to the gonads where they activate cell-surface receptors on the spermatogonia. Good p-fitness results in the recombination hot spots of the spermatogonia being stabilized, whereas poor p-fitness results in their further destabilization. 

Thus, good p-fitness leads to good penetrance of the paternal recombinotype into viable sperm, whereas poor p-fitness leads to poor penetrance because of many further crossing-over events. Changes in hotspot activity could possibly be due to changes in cytosine methylation status. The result is within-lifetime changes in idiosyncratotype frequencies in the population, leading to changes in the gross behavior of the population in a way that favors species survival in the face of environmental fluctuations on an oligo-generational timescale. On such a timescale, neither standard natural selection nor synapse-based learning systems are serviceable.

Female PGS Is Different 

However, egg cells mature in utero and therefore face a selection disconnect or delay. The female version of crossing over may set up a slow, random process of recombination that works in the background to gradually erase any improbable statistical distribution of recombinotypes that is not being actively maintained by PGS.

A Better Theory of Female PGS 

First, a definition. PGS focus: a function that is the target of most PGS. Thus, in trees, the PGS focus might be bio-elaboration of natural pesticides. In human males, the PGS focus might be brain development and the broad outlines of emotional reactivity, and thus behaviour. In human females, the PGS focus might be the digestive process. The effectiveness of the latter could be evaluated while the female fetus is still in the womb, when the eggs are developing. The proxy fitness measure would be how well nourished the fetus is, which requires no sensory experience. This explains the developmental timing difference between oogenesis and spermatogenesis. Digestion would be fine tuned by the females for whatever types of food happen to be available in a given time and place.

Experimental evidence for the proposed recombination mechanism of PGS has been available since 2011, as follows:

Stress-induced recombination and the mechanism of evolvability

by Weihao Zhong; Nicholas K. Priest

Behavioral Ecology and Sociobiology, 03/2011, Volume 65, Issue 3

Abstract:

“The concept of evolvability is controversial. To some, it is simply a measure of the standing genetic variation in a population and can be captured by the narrow-sense heritability (h2). To others, evolvability refers to the capacity to generate heritable phenotypic variation. Many scientists, including Darwin, have argued that environmental variation can generate heritable phenotypic variation. However, their theories have been difficult to test.

 Recent theory on the evolution of sex and recombination provides a much simpler framework for evaluating evolvability. It shows that modifiers of recombination can increase in prevalence whenever low fitness individuals produce proportionately more recombinant offspring. Because recombination can generate heritable variation, stress-induced recombination might be a plausible mechanism of evolvability if populations exhibit a negative relationship between fitness and recombination. Here we use the fruit fly, Drosophila melanogaster, to test for this relationship.

We exposed females to mating stress, heat shock or cold shock and measured the temporary changes that occurred in reproductive output and the rate of chromosomal recombination. We found that each stress treatment increased the rate of recombination and that heat shock, but not mating stress or cold shock, generated a negative relationship between reproductive output and recombination rate. The negative relationship was absent in the low-stress controls, which suggests that fitness and recombination may only be associated under stressful conditions. Taken together, these findings suggest that stress-induced recombination might be a mechanism of evolvability.”

However, my theory also has a macro aspect, namely that the definition of what constitutes "stress," in terms of neuron interconnections or chemical signalling pathways, itself  evolves, by species-replacement group selection.

#7. What is Intelligence? Part I. DNA as Knowledge Base [genetics, engineering]

EN   GE

Red: theory; black, fact

The Known Intelligences 

There may be three intelligences: the genetic, the synaptic, and the artificial. The first includes genetic phenomena and may be the scientifically accessible reality behind the concept of God. The synaptic is the intelligence in your head, and seems to be the hardest to study and the one most in need of elucidation. The artificial is the computer, and because we built it ourselves, we understand it. Thus, it can provide a wealth of insights into the nature of the other two intelligences and a vocabulary for discussing them.

The Artificial Intelligence 

Artificial intelligence systems are classically large knowledge bases (KBs), each animated by a relatively small, general-purpose program, the "inference engine." The knowledge bases are lists of if-then rules. The “if” keyword introduces a logical expression (the condition) that must be true to prevent control from immediately passing to the next rule, and the “then” keyword introduces a block of actions the computer is to take if the condition is true. Classical AI suffers from the problem that as the number of if-then rules increases, operation speed decreases dramatically due to an effect called the combinatorial explosion.

DNA Through an AI Lens

A genome can be compared to a KB in that it contains structural genes and cis-acting control elements. The latter trigger the transcription of the structural genes into messenger RNAs in response to environmental factors and these are then translated into proteins that have some effect on cell behavior. The analogy to a list of if-then rules is obvious. A control element evaluates the “if” condition and the conditionally translated protein enables the “action” taken by the cell if the condition is true.

Avoiding Slowdowns at Scale

Note that the structural gene of one rule precedes the control element of the next rule along the DNA strand. Would this circumstance not also represent information? However, what could it be used for?

It could be used to order the rules along the DNA strand in the same sequence as the temporal sequence in which the rules are normally applied, given the current state of the organism’s world. This seems to be a possible solution to the combinatorial explosion problem, leading to much shorter delays on average for the transcriptase complex to arrive where it is needed. I suspect that someday, it will be to this specific arrangement that the word “intelligence” will refer.

A Rule-ordering Mechanism 

The process of putting the rules into an efficient sequence may involve trial-and-error, with transposon jumping providing the random variation on which selection operates. 

A variant on this process would involve the enhancement by de-methylation of recombination sites that have recently produced successful results. These results would initially be encoded in the organism's emotions, as a proxy to reproductive success. In this form, the signal can be rapidly amplified by inter-individual positive feedback effects such as competition. It would then be converted into patterns of DNA de-methylation in the germ line. DNA methylation is known to be able to cool recombination hot spots, so de-methylation should do the opposite.

Rule Creation 

A longer-timescale process involving meiotic crossing-over may create novel rules of conduct by breaking DNA between promoter and structural gene of the same rule, a process analogous to the random-move generation discussed in my post on dreaming. Presumably, the longest-timescale process would be creating individual promoters and structural genes with new capabilities of recognition and effects produced, respectively. This would happen by point mutation and classical selection.

Implementing Jump Instructions In DNA 

How would the genetic intelligence handle conditional rule firing probabilities in the medium to low range, which would call for jump instructions as opposed to merely incrementing the instruction pointer?

This could be done by cross linking nucleosomes via the histone side chains in such a way as to cluster the cis control elements of likely-to-fire-next rules near the end of the relevant structural gene, by drawing together points on different loops of DNA. The analogy here would be to a science-fictional “wormhole” from one part of space to another via a higher-dimensional embedding space. In this case, “space” is the one-dimensional DNA sequence with distances measured in kilobases, and the higher-dimensional embedding space is the three-dimensional physical space of the cell nucleus.

A Possible Mechanism of Jump Instructions 

The cross linking is presumably created and/or stabilized by the diverse epigenetic marks known to be deposited in chromatin. Most of these marks will certainly change the electric charge and/or the hydrophobicity of amino acid residues on the histone side chains. Charge and hydrophobicity are crucial factors in ionic bonding between proteins. A variety of such changes are possible.

Another way of accounting for the diversity of epigenetic marks, mostly due to the diversity of histone marks, is to suppose that they can be paired up into negative-positive, lock-key partnerships, each serving to stabilize by ionic bonding all the wormholes in a subset of the chromatin that deals with a particular function of life. The number of such pairs would equal the number of functions. Their lock-key specificity would prevent wormholes, or jumps, from forming between different functions, which would cause chaos.

Evolutionary History of Jump Instructions 

If the eukaryotic cell is descended from a spheriodal array of prokaryotes with internal division of labor and specialization, then by one simple scheme, the specialist subtypes would be defined and organized by something like mathematical array indexes. For parsimony, assume that these array indexes are the different kinds of histone marks, and that they simultaneously are used to stabilize specialist-specific wormholes. A given lock-key pair would wormhole specifically across regions of the shared genome not needed by that particular specialist.

A secondary function of the array indexes would be to implement wormholes that execute between-blocks jumps within the specialist's own program-like KB. With consolidation of most genetic material in a nucleus, the histone marks would serve only to produce these secondary kind of jumps while keeping functions separate and maintaining an informational link to the ancestral cytoplasmic compartment. The latter could be the basis of sorting processes within the modern eukaryotic cell.