Genetics is like a musical score

Amadeus Mozart and Ludwig van Beethoven may be the most genetically studied musicians of all time. Why is that? Because their music is famous and loved? Because their personal history is full of celebrity and drama? Or are they just favorites of geneticists?

The narrative in most of the published studies is to understand the interaction between musical sounds and humans. I'm still not sure if this can be completely solved because music is more than just sound. It is a musical 'language', with or without words, that interacts with with the human mind and body. However, because we are a curious species, we seek to learn about those connections. And, as I suspect, the two famous composers have had a growing foundation of research on which to build upon. 

A recent study* explores if genetic factors can determine extraordinary musical achievements. If that is so, then how do genes contribute or determine a person's musicality? This isn't a new query; geneticists have examined similar questions by studying the two famous composers for decades. However, recent advancements in molecular genetics allow scientists to probe deeper into human DNA, sometimes restudying old questions or asking new ones, especially of long-dead people.

Then again, when studying humans, sometimes these newer studies only confirm older results. 

“An analysis of the famous composer's genetic make-up has revealed that DNA data has so far been too imprecise in capturing a person's abilities.” 

In this recent study, an international team of researchers analyzed Beethoven’s DNA to investigate if and how any differences in his genes may account for his celebrated musical exceptionalism. 

The deeper question is, how much can genes impact human traits, especially behavior? When considering a bird or a lizard, probably quite a bit. But humans are “messy.” There is no single quantitative or qualitative line that divides genetically determined and learned human behavior. This is the age-old “nature versus nurture” dilemma. The lines are fuzzy.

Ludwig van Beethoven was born in Bonn (a major city in Germany), which was at that time the capital of the Electorate of Cologne and partly dominated by Roman archbishops. He moved to Vienna (1792), Austria, to flee a dysfunctional family and meet other musicians. 

During this time in history Napoleon restructured France (1789) and regions north including Bonn (1794) and Vienna (1805) after the famous French revolution. Beethoven supported Napoleon's reformations and composed his famous third symphony naming it “Napoleon”.  After Napoleon proclaimed himself Emperor (1804) Beethoven rescinded the Napoleon dedication and renamed it “Eroica”. He even refused to play this symphony in front of French soldiers.

Beethoven lived during a tumultuous era of wars and conflicts with rulers. It was the rise of the German Enlightenment period, transition from the Classical to Romantic era in art and music, almost constant family turmoil, and loss of hearing. He was a man full of emotion, conviction, and righteousness. As his music conveys, he was a man with passion. Are there genes for that?

The researchers analyzed DNA sequences available from an earlier study (2023) in which the composer’s DNA was extracted from strands of Beethoven's hair. The authors then developed a ‘polygenic score’, a number that summarizes the estimated effect of many genetic variants on an individual's trait or behavior. 

"Our aim was to use this polygenic score as an example of the challenges of making genetic predictions for an individual that lived over 200 years ago.”

They chose a specific component of music that had a score for “beat synchronization ability”, which is closely related to musicality. Beat perception and synchronization in humans is the degree to which an individual can synchronize their movements in time with a musical beat. In humans, it is commonly within 120 to 140 beats/minute and is frequently used in music composition. Ironically, beat synchronization was thought to be uncommon in non-human species and the mechanism determining the optimal tempo are unclear.

Although this was thought to be a human rhythm trait, a study in rats (2022) revealed that rats also showed head movements and neural recordings within the same range as humans. This suggests that "the optimal tempo for beat synchronization is determined by the time constant of neural dynamics conserved across species".

And Beethoven?

"The study found that Beethoven had an unremarkable polygenic score for general musicality compared to population samples from the Karolinska Institute, Sweden, and Vanderbilt University, USA. However, considering the limitations of the current polygenic scores and the fact that a genetic indicator for ‘beat synchronization ability’ may not directly tap into Beethoven’s composer skills (musical creativity), this finding is not unexpected.”

The genetic architecture of this trait is highly polygenic, meaning that it is influenced by many genes in the human genome. Authors identified 69 separate locations on the genome in which different genetic alleles (every person has two copies of a gene; they are called 'alleles') in the population account for some of the variability in how accurately people synchronize to a musical beat. 

Genes associated with beat synchronization are more likely to be genes involved in central nervous system function, including genes expressed in brain tissue and genes involved in early brain development. Recent studies also found that beat synchronization shares some of its genetic architecture with other traits, including several that are involved in biological rhythms (walking, breathing, and circadian rhythm). 

The polygenic score computes the sum of genetic effects associated with beat synchronization in each individual, but they are only a rough guess. It can tell us only what an individual’s likelihood of specific levels of beat synchronization would be in relation to the population-based model, but they do not correspond directly to an exact match with the person’s beat synchronization accuracy. Thus a person's beat synchronization may be a point amongst many in a wide area under the curve. And Beethoven's score may be lower than expected, but did that negatively impact his compositions?

“Although Beethoven had a rather low genetic predisposition for beat synchronization highlights the limitations of polygenic score predictions at the individual level. While polygenic score prediction is expected to get more accurate in the future, it is important to remember that complex human traits, including musical skills, are not determined solely by genes or the environment but rather shaped by their complex interplay.”

In conclusion the authors stated that the current study "only shows that we’ve been able to use genetics to explain a portion of the variability in beat synchronization skills (again, at the level of pooled data in a large study sample)."

When scientists talk about “heritability” they are referring to the amount of phenotypic variance explained by genetic variation. This does not mean that rhythm is only “genetic” versus only “environmental,” or that rhythm is genetic in certain people but not others.

"Scientifically we really can’t say for sure how and why an individual reaches (or does not reach) a certain level of musicality. So it’s not “either-or” but “both-and” genes and environment, and the incredibly complex biological interrelationships that occur during human development of musicality will take many, many more years of work to unravel!"

Studies of beat synchronization in humans and other species, such as in rats, found interesting genetic correlations between beat synchronization and a cluster of interrelated traits: walking pace, musculoskeletal strength, breathing function, and cognitive processing speed. Possibly even cadence in language! Additionally, the shared genetic architecture has implications for physical and cognitive function in neurodiverse people and during aging.

* "Was Beethoven unmusical?", Max-Planck-Gesellschaft Research News, published on website April 10, 2024 and accessed 20/08/2024.

Pangea gone wild

Pangea and the diversity of life. 

Most everyone knows what Pangea was: the largest supercontinent in Earth's history. All land masses united in a large group gathered together for a conference. They also shared all organisms on their surfaces before splitting into individual continents. 

This split didn't magically happen like many people think. It was a very long process. Pangea split into unequal halves forming two supercontinents: Laurasia and Gondwana. Additionally, these two landmasses continued sharing some flora and fauna over a long period of time.

Over millions of years further tectonic activity caused Laurasia and Gonwana to split into smaller landmasses gradually forming the continents we are familiar with today. This long process was a key impact on early evolution of both flora and fauna. 

The expanding distance between continents reduced exchanges of flora and fauna, eventually isolating many groups of life. Some fauna continued dispersal from continent to continent by rafts of islands or ice. Others migrated by air (e.g.seed and flying animals). Our knowledge of the degree of and when continental shifting impacted evolution of flora and fauna is continually evolving (pun intended) in the field of biogeography. There are two theories:

"Do new species come from animals populating new territory (called dispersal), or did populations get separated during Earth’s breakup (called vicariance)?"

We know that both dispersal and vicariance played roles in early evolution of nearly all flora and fauna. And we need to consider that distribution of life occurred over a long periods of time, even during different stages in the evolution of flora and fauna. Local, regional and continental changes in topography or climate can influence dispersal of isolated populations. It can also expand habitats for others enabling mixing of populations where isolation barriers once existed. 

Several approaches can help elucidate the contribution of vicariance or dispersal at different points of an organism's evolution. The most valuable is phylogenic trees, structural diagrams that represent evolutionary relationships among organisms. The pattern of branching in these trees reflects how groups and individuals of  organisms evolved from a series of common ancestors and their predicted evolutionary timing. They are evolutionary 'trees'. 

A group of scientists used the data within a set called the Timetree of Life. It is a phylogenic tree of life scaled to time. Using data for major freshwater and terrestrial vertebrate groups (animals with backbones: fish, amphibians, reptiles, birds and mammals) that were descended from common ancestors and represented on at least two continents, they examined when they diverged. 

Dates of divergence of those groups separated by continents lined up with the continents geographically separating. This supports the theory of vicariance over dispersal as the major cause for speciation. However, this may change as the data sets change. 

There are considerations that may impact this theory. One is the contribution of moving pieces of land, such as land bridges. Another is narrow bodies of water separating the shifting continents and facilitating both flora and land dispersal. 

As the author of the article highlighting the study commented, "this paper is swinging the pendulum between two competing ideas". And, as science is sometimes fraught with binary thinking, the two theories don't have to be a "competition", or mutually exclusive. Life isn't A or B; it is a dynamic collection of events that can happen together or seamlessly flow from one to the other. Generalizations don't always pan(gea) out. 

Humans are not islands

"Pathosystem" 

I like that term. It encompasses a systems perspective -both pathogen and host- rather than focusing on just a single component of a system. It is an ecosystems perspective with emphasis on pathogen-host-environment. 

My academic career spanned plant, animal and human pathology (except for the last several years in physiology). A systems perspective is always inherent in the first two, less so in human pathology. It's as if Descartes binary philosophy (separation of mind and body) extended to separation of body and the environment in which bodies exist. As medical specialization demonstrates, even separation of organs from the rest of the body. 

I have wondered if this might be a contributing factor in some of the failures of modern medicine. An example is the lack of translational research of human psychology and medicine. 

The prime example is diabetes: lot of research in physiology and pharmacology, but little research and application of how/what to inform and impact people to change and adopt behaviors that prevent and reduce diabetes. This extends also to social systems: education, policy, connecting the production, supply and access of nutritious food. 

We know how this works and how to achieve these goals with plants and animals. And we practice it, most of the time. The question is why can't we do it for ourselves, and other people? 

This is what we really need to focus on. It's that part of the 'ecosystem' that is dysfunctional. Science should be the leader in this. 

Why isn't it? Has that failed us, too?

History of obesity. In Denmark.

“The origins of the obesity epidemic may be further back than we thought”

A recently published paper concluded that the rise of obesity began earlier than conventionally assumed. (See article summarizing study: The Origins of Obesity in Science.)

"This study revealed that continuous steady increases since the interwar period in the upper percentiles of the BMI distribution preceded the obesity epidemic, with an almost similar pattern in the children and the young men." (published paper)

I agree with some of the criticisms of the study and conclusions, such as population sample=1 (Denmark). Is this trend replicated in other countries? 

Another comment from a biostatistician that “slow and steady increases in obesity don’t necessarily indicate an earlier onset of the epidemic [of obesity]”. A proper data pool for that would require data before 1930’s. 

A statement from the original published paper confirms my observation over the years traveling this country: “The acceleration of the obesity epidemic has been stronger in rural and provincial areas than in densely populated urban areas, which was seen already in the beginning of the rise of prevalence in obesity in Danish young men during the 1960s.”

And, like anything involving human behavior, the contributions are multifactorial.

The high prevalence of obesity in people of all ages in rural Ohio was a shock when I moved there in late 2001. 

During a conversation on this subject with a man (late 20’s) that I was training, he commented that as agriculture became industrialized it required less physical activity by all family members. However, the culture of food and eating amongst farm families remained the same: calorically dense food, especially fats, and large portions during meals. 

Consequently, while activity levels decreased, the energy balance became very skewed towards a positive high caloric net balance. Which, over time, results in increased body mass.  

We can see an eventual similar trend in urban areas over time, albeit slower. My hypothesis is that most rural families used to grow their own food, meat and vegetables/grains. So they had an almost guaranteed supply of food and energy. 

Urban people had to purchase all their food (and still do). Purchasing power for food was based on their incomes and other debts (rent, etc). History worldwide has shown that wealthy people always have had almost unrestricted access to food. For many centuries, being overweight was a social sign of being affluent. 

It was only during the last half century when increasingly more people began moving from rural to urban communities. Industrial agriculture and food processing caused a large shift in the nutritional content and availability of food, and the culture of food. 

As Gary said that day, “People of Ohio still love their corn and pork, and there is plenty of it here. But now everyone has desk and ‘standing still’ jobs. And the kids don’t play as much; they’re glued to their phones and video games.”

Quantum evolution

To fully understand evolution, and life itself, one must be able to grasp quantum theory (quantum mechanics is mostly mathematical equations at the microscopic level and not at all required to conceptually understand quantum systems). General relativity is also a quantum system. 

Seeing time only through clocks and calendars will never give us any kind of appreciation of time on a larger scale. Those are metrics, but are not really time itself. Same with evolution: it exists at many points and flows back and forth. It really can't fit into what we consider as 'time'.  

Biophysicist Werner Loewenstein succinctly presents evolution as a quantum system of information.*  Rather than thinking of evolution following a linear path in time, it is information in the quantum realm, constantly shifting places like tiny sand particles on an ocean beach. 

Thus, evolution is chunks of information existing in the future and the past. What we see is how it manifests only at any point within that realm. There is no moment of 'creation' just as there is no moment of 'end'. Species don't magically appear; they evolve, and devolve. 

"It is difficult to even talk about an instant of time, because we can’t even say with certainty which “chunks” of space-time lie in the future and which in the past." -physicist Jonathan Oppenheim 

Evolution requires us to jump off that restrictive scale and think in terms of shifting sands.

* The Touchstone of Life. Werner Loewenstein, 1998.

Muscles don't have memories!!

Peeve: When the scientific community can't agree on a definition consensus for a term, such as 'muscle memory'. 

Muscles don't have memories. Brains do. 

Ask anyone in a gym and you'll get four or more interpretations of what 'muscle memory' is or means. Ask scientists and you'll get one of three; each thinking they offer the only correct definition. 

This was a frequent source of amusement in our lab (neuromuscular pathology); we agreed to avoid the term unless being sarcastic. We often used the general term 'muscle plasticity': the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed. That's what muscles do. 

Then, what IS muscle memory?

According to Wikipedia (and a more summarized definition in Oxford Dictionary), 'muscle memory' is:

"...a form of procedural memory that involves consolidating a specific motor task into memory through repetition, which has been used synonymously with motor learning. When a movement is repeated over time, the brain creates a long-term muscle memory for that task, eventually allowing it to be performed with little to no conscious effort. This process decreases the need for attention and creates maximum efficiency within the motor and memory systems."

So, what is muscle plasticity? 

Phenotypic* plasticity allows single genotypes to express different phenotypes under diverse environmental conditions. Organisms, and tissues (some more than others), respond to different environments by changing how they act, look or function. Skeletal muscle is a highly plastic tissue. 

For example, exercise initiates signaling pathways that modify muscle fiber metabolic, physiological and contractile properties of skeletal muscle (sometimes referred to as 'remodeling'). That is 'muscle plasticity'. Whereas exercise can also evoke memories (conscious and subconscious) in the brain of how movements are executed. It is a back-and-forth communication between muscles and the brain via the central nervous system. That is  'muscle memory'.

In language, adjectives connote specificity. In particular, 'neuromuscular plasticity' and pathology were the focus of our research. Muscle plasticity requires the coordinated interaction between neurons and muscles, but pathology narrows the focus. Disease or injury of motor system components, including responsive proteins in muscle fibers, can lead to muscular motor dysfunction. Like all tissues, biological/molecular processes are included. 

One example is muscular dystrophy: a disease in which one or more muscle proteins are absent or dysfunctional because of genetic aberrations that interrupt the signal between the motor neurons and the ability of the muscle to respond. It has little if anything to do with procedural memories, aka 'muscle memories', in the brain. A muscle group without dystrophin won't be able to contract, irrespective of any 'muscle memory' in the brain. 

Using the correct language is imperative for science communication within the scientific community. Incorrect** and vague terms are perpetuated throughout communication and education (formal and informal) outside of that community, such as with medical professionals, trainers, social media, etc. Yet confusion remains if members of the scientific community do not consistently use correct definitions of terms. This needs fixing.

Summarily, the use of the term 'muscle memory' should be restricted to the associations of movement and 'memories' established in the brain. Better yet, these terms are better:

• Procedural memory ( or 'Kinesthetic memory'): the automatic movements involved in throwing a ball, dancing, swimming, steering a vehicle, typing, or even squats.), or
• Motor memory:  process by which animals can adopt both persistent and flexible motor behaviors. 
  
  

MUSCLES DON'T HAVE MEMORIES!
Brains do.

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* Phenotypic is the observable traits of an individual resulting from the interaction of its genes (genotype) and its environment. 

** Many researchers have recently published papers in scientific journals and still use the term 'muscle memory' in the context of muscle biology/molecular biology and physiology without ANY reference to -'memories' formed and stored in the brain! 

Being inside out

Modern biotechnology is wonderful. It reveals wonders that we can't see without it. It tells us more about ourselves and about each other, about living things that surround us. Ironically we can see inside our bodies, but still scratch our heads on the outside wondering how we tick inside our brains.

Many years ago, while spending days [1] extracting DNA from large quantities of white blood cells from cows' blood, I added a small tube of my own WBCs. There was room in the centrifuge; why not? The feeling of seeing thin threads of your own DNA floating in solution inside a gently rocking test tube is inexplicable. 

Those fine threads were a history catalog of generations before me, before my mother and father, before them. They were strings of time more ancient that any of us can fathom, carrying the instructions on what makes me human. And how similar yet different I am from each of you. Ironically, even similar to the thick ropes of cow DNA rocking alongside in their own test tubes.

Trypanosoma theirleri and red blood cells

[1] I collaborated with a colleague to develop a sensitive assay (PCR) for detection of microscopic single-celled parasites (Trypanosomes) in the blood of cows. They literally beat up blood (red and white) cells with their 'tails' (flagellum) and weaken the animal's immune system. The process entailed extracting DNA from the fraction of liters of blood containing the WBC; in that fraction were the parasites and their DNA. A close 'cousin' of the same parasite causes Sleeping Sickness in humans.

An American Mutt (revised 12.2022)

Like most Americans I'm a 'mutt': a combination of different nationalities, rather than one identifiable national identity. Maybe I'm the only one that admits it, and proud of it. Also fitting, considering my inexplicable interest, both scientifically and personally, in canids. All canids, not just dogs and wolves.

I'm a mutt through and through. So my loyalties extend to all people and almost all real canids (those tiny dogs just aren't real canids; they're genetic mistakes).

I grew up not fitting in anywhere. And not really understanding that until I spent a summer in the Middle East and Europe. Then I realized I'm simply a member of the human race. That's all I needed to know.

We're all human.

There are no sub-species for Homo sapiens. Yet we act like there are. Our species is a very tribal one. We look for anything to belong to and separate our selves from others, pledging loyalty to this and that, and resenting any group that doesn't match our criteria. Our species is in a perpetual identity crisis.

I blame it on taxonomy. Anyone in biological sciences is bottle fed systematics: the classification of every life form. Taxonomy is a scheme of classification, usually in a hierarchical approach in which living things are organized into groups or types. People classify themselves the same way.

People born in Greece are Greeks; in Mexico, Mexicans; in America, Americans. People born in the Britain are Brits. However, if I were born in Scotland, a member of Britain, I'd be both a Brit and a Scot.

I was born in the United States of America and legally, I am an American. But I really don't feel like one. At least, not compared to how many of my fellow American citizens feel 'American'. I don't share the tribal loyalty (often blind) that many do.

So what am I?

I'm what??

My last name comes from Germany and my first name is a corrupted form of the German/Scottish/English 'Elspet/Elspeth/Elizabeth'. (Even my name is a mutt.) American names aren't original; they are fragments from many countries strung together to label a person accompanied by a unique social security number. The latter is what makes us American.

Because my parents rarely talked about their family history, my sister and I researched our family genealogy after they passed on. The patriarchal tree is relatively simple: married immigrants from Bavaria arrive at Ellis Island in 1861 with their five children, settle in Buffalo, NY, and birth six more children. Most of the male offspring married Irish or Scottish women, who also had up to 12 children, and so on. Ironically, many of the female offspring are dead ends: once they marry, their adopted husband's last names render them lost in history.

I'm fourth generation American-German.

The matriarchal tree is even simpler: my maternal grandmother was born in Sweden. Her parents were born in Sweden. That was easy. That makes me second generation American-Swedish.

I did what many people are doing now: ancestry DNA. I discovered that human DNA is much more complicated than the bacterial and viral DNA I was used to be. Like any genetics project, genetic information is dependent on data derived from a population of samples. If that sample pool is small, the data is also limited and may not represent the larger population. Also, as gene sequencing technology changes, so does the size and confidence of the data. Consequently, as more genetic data from people around the world are added to central databases, the more precise the genetic information of ancestors. It also adds to the histories of human migration over thousands of years.

One genealogy autosomal DNA analysis reported that I am 68% Scottish/Irish, 19% Scandinavian, and......13% German*?? Another analysis reported 44% German, 19% British Isles, 14% Slavic**, 11% Italian, and the small balance Scandanavian (2%), French, and 2%.... Peruvian??

Oh, what the hell.....  I'm a mutt. And proud of it.

*It's more complicated than that. What DNA companies don't explain (except for CRI Genetics) is that a person's DNA does not give a crap about labels and borders. The reason many people with known German ancestry are pinned to the United Kingdom, or other modern countries, is because Germany was not a unified country with a common border until 1871. Before then, the region was occupied by many ethnic groups: Romans, Germanic tribes, Celts, and, going back to the Bronze Age, the Yamnaya (originally from the steppes of western Russia). For example: Bavaria was a 'hot spot' of migration mixing.

** Preliminary online research into Scandanavian DNA projects, the Finnish DNA Project (Finnish DNA Reference Group) shed some insight into the Slavic connections. Although mtDNA (DNA from female mitochondria) provides more exact information (especially, haplotypes), "Overall, as we know from autosomal studies, Finnish ancestry derives primarily from Europe, especially the Baltic region". Many Finns migrated and settled in Norway and Sweden. That explains the Slavic connection. 

We are all mutts.

For those interested in the seven-year 1000 Genomes Project, this link leads to a summary of the project (published 2015 in Nature journal).  Data from diverse human populations, such as the Finnish Project mentioned, continue to be added. This and other smaller genome projects (e.g. link to overview of UK genome projects) serve as a basis for genetic genealogy data sources used by commercial DNA/genealogy analyses. The current expansion of this effort can be found at The International Genome Sample Resource. 

"1000 Genomes Project publishes its final two papers, which analyze 2,504 genomes from 26 populations and provide the most comprehensive view of global human variation so far."

Are we breeding for stupid dogs?

 "Little brainiacs and big dummies: Are we selecting for stupid, stout, or small dogs?"

Intriguing study. The title is catchy, so I read it. 

A general scaling quotient related to brain size, or encephalization, for all mammals is defined as the amount of brain mass exceeding that related to an animal's total body mass. Brain size non-linearly scales with body weight between species within mammals to around the 0.67 power. However, within species, this scaling exponent appears to be much smaller. An early study compares dogs with non-canid species. According to this study, we are breeding dogs to have smaller brains. 

Dogs today have smaller relative brain size than dogs 100 years ago. That may not be an intention, but we do selectively breed them for certain behavioral traits as well as well as physical appearance. The famous Russian Silver Fox experiment confirms that (6 generations of breeding and choosing individuals for tameness resulted in a domestic fox). Keep in mind that genes linked to behavior and physical appearances may be linked to brain size. 

This encephalization quotient generally estimates 'evolved intelligence' or other behavioral traits, "under the assumption that the bigger the brain per kilogram of bodyweight beyond what would be required for basic neural functions, the greater the intelligence." But have we humans also bred for lower brain function? aka 'stupid' dogs?

My interest was more in how this compares to non-dog canids than within domestic dogs. A phenomenal earlier study* (1986) compared brain size and weight between all families within the carnivore order (all carnivore families, genera and most species). The study also used metrics including ecology and behavior as well as body and brain size, developing an encephalitic quotient (EQ) range. Canids placed in between the families Ursidae (bear family) and felids (cats). 

What is interesting is the EQ within domestic dogs compared to the within species of non-dog EQ. The current study found that EQ decreases with increasing body weight in dogs: "Small dogs had higher EQ than their non-dog canid counterparts of comparable size, but large dogs had lower EQ than similarly sized non-dog canids."

Encephalization quotient decreases with increasing body weight in dogs. The dashed black line represents the regression line for dogs, the dark gray solid line represents the regression line for dogs from the Richet dataset, and the light gray solid line represents the regression line for canids from the Gittleman dataset. The regression line for canids crosses the regression lines for dogs at approximately 10–15 kg.

In other words, domestic dogs have a brain-size-to-body-size relationship that markedly differs from the general rule between-species relationship (power function of 0.26 rather than 0.65–0.67). That's quite a difference. 

But this is even more impressive: modern dogs have lower relative brain sizes than dogs of a century ago. There are two possible biological explanations. First, humans purposely select for smaller heads, which includes the size of the cranium. This is unlikely. 

The second and more likely explanation is that modern dogs are fatter than their lighter counterparts from a century ago: "...plentiful evidence exists that dogs, like people, in the United States are experiencing an increasing prevalence of obesity." 

Authors in the recent study recognize an important methodological criteria related to the above explanation: "Researchers a century ago recognized the importance of examining brain-size-to-body-size relationships in animals that are in 'optimal condition,' and cautioned including data for domestic animals that often differ in body condition from their wild counterparts." Definitely true. Regardless, the prevalence of obesity in dogs (and humans) is concerning. 

What about intelligence? Are bigger dogs smarter than small dogs due to brain size, or vice versa?

Despite common beliefs we all hear, the authors conclude "no behavioral evidence exists that small breed dogs are more intelligent than large breed dogs." Most of us know that behavioral studies are fraught with discrepancies in methodology and interpretation. Additionally, several studies failed to observe a relationship between brain size and cognition. Some studies have reported that certain breeds are more "trainable" or perform better at certain skills. Similar reports are associated with horse breeds.

The authors offer a more plausible explanation; what these studies and anecdotal claims more correctly identify is a "selection of specific morphotypes for specific tasks, and certain cognitive skills that underpin those tasks, rather than selecting for or against overall intelligence." Specific physical attributes are more suited for specific tasks and skills than others, and behavior is a result of genes and learning. 

"Such a hypothesis finds support in studies that identify “trainability” with working breeds vs. non-working breeds, rather than size. Given that working breeds are generally larger than non-working breeds, size might simply be a poor surrogate for “working breed.”

I enjoy good challenges (and controversies) in biology. They force people to critically think (and they should). The authors in this study challenge existing and generalized assumptions about interpretations and conclusions relating to differences in body sizes with a subtle hint of well-deserved sarcasm. 

"This observation flies in the face of assigning an encephalization quotient to dogs—in our study, small breed dogs had a relative brain size far exceeding their “expected” brain size, while large and giant breed dogs had relative brain sizes of mental midgets. Therefore, applying an encephalization quotient to dog breeds appears nonsensical, and challenges the entire anthropocentric notion of encephalization as a measure of intelligence."

This, to me, is the coup d'état challenge for scientists that arrive at assumptions and generalizations that persist on shaky evidence. It also represents a challenge to those that choose and pick their data or facts to support their preconceived assumptions. In this case, the challenge is how we perceive intelligence in dogs, and perhaps all animals. Including our own genus, Homo spp.**

Read the last two paragraphs of the paper where the authors discuss "What makes a dog a dog?" and how selecting for smallness has a limit (which it does, so stop it). 

"....regardless of how small domestic dogs become, brain size must be conserved to accommodate sufficient neuronal complexity for the dog to maintain its “dogness.”

In all, excellent discussion and writing for a published scientific paper.  

* Gittleman J.L. Carnivore brain size, behavioral ecology, and phylogeny. J. Mammal. 1986;67:23–36.

** A recent article (sometime in March 2021) challenged our modern assumptions about the inferior intelligence, or lack of, in Neandertals and Denisovans. You'll have to do a google search for that article. 

Oh, Phosphorus. How art thou?

I'm bored with spinning, TV and reading my books. It's cold and raining outside. So I'm reading a few papers on how phosphates evolved to facilitate biological life. Physics, chemistry and information theory. 

The word phosphorus derives from the Greek phōsphoros: phōs ‘light’ + -phoros ‘-bringing’. Perhaps the Greeks knew more than we do.

I asked this question of my graduate biochemistry instructor: "How did phosphorus evolve to be the key element of life?". She just shook her head and answered, "You just have to sometimes accept that we don't have the answers, that we just don't know."

"Nah. I bet we do, or will soon."

That was in the mid-1980's. Westheimer published a paper, "Why nature chose phosphates", in 1987 proposing a theory (partly) answering my question. His theory was refined in 2013 by Kamerlin, et al: "Why nature really chose phosphates." Then, Liu et al took it to a different level with "How Prebiotic Chemistry and Early Life Chose Phosphate". 

Goldford, et al. commented in the introduction of their paper ("Remnants of an Ancient Metabolism without Phosphate," 2017), "Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility." But we now know how phosphates assumed that essential role. 

Hess et al published earlier this year (Nature,16 March 2021) another theory,
"Lightning strikes as a major facilitator of prebiotic phosphorus reduction on early Earth". (Remember the Greeks?) It circles back to biophysicist Werner Loewenstein's 1999 book ("Touchstone of Life") in which he explains why lightening probably facilitated phosphorus being the first and basic element for life on Earth (and may be on other planets). This book is enlightening for integrating information theory, physics, chemistry, and molecular biology. (One star of the book is Maxwell's demon.)

But, wait! A treatise explores the 'phosphorus enigma' at the largest scale: the book, "The Chemical Evolution of Phosphorus: An Interdisciplinary Approach to Astrobiology" (Enrique Maci -Barber, PhD, Professor of Condensed Matter Physics in Madrid, Spain). In the forward of the book, Sun Kwok (astronomer studying the physics and chemistry of stellar evolution) wrote:

"This book beautifully traces the stellar origin of the element phosphorous, its chemical properties, and the observations of phosphorous-based molecules and minerals in the interstellar medium and in the solar system. [The author] then connects the astronomical studies with the role of phosphorous played in living organisms, presenting the biochemistry of biomolecules that incorporate phosphorous, and the roles that these molecules play in the origin of life on Earth."

Unfortunately, the book is also a hefty $150; far out of my price range. 

Branching off but parallel to the road of physics and chemistry, information theory has expanded understanding of prebiotic and current life. My first introduction into this was more like an epiphany while reading Loewenstein's book when it appeared on the shelves in 1999. It filled in the gaps for a continuing passion of concepts in cell signaling. It wasn't just about chemistry; physics was the parent. (College physics, taught only as mechanical physics, turned me off to the subject. I endearing called  it "'fysics; the other 'f' word". Despite that my father, a biophysicist/biochemist, tried to convince me to not ignore 'fysics'.)

Realistically, information theory integrates physics, chemistry, molecular biology, structural biology, geology, and more. It's like a spider web with life (and death) at its core. Whenever anyone, especially during this pandemic, mentions the spike protein and ACE2 receptor, antibodies and ligand, and, especially, the immune system, my immediate response is "Conformation is everything", a mantra I picked up  in biochemistry and incessantly repeat. (Network theory, inclusive of information theory, is now being applied to the immune system.)

Dr. Chris Adami, theoretical physicist and computational biologist, is the one of the few researchers using information theory to understand the physical and medical sciences and evolution. Life should not be thought in terms of chemical events. Instead, it should be thought of as information transmission. Adami comments during an interview:

"Information is the currency of life. One definition of information is the ability to make predictions with a likelihood better than chance. That’s what any living organism needs to be able to do, because if you can do that, you’re surviving at a higher rate... Think of evolution as a process where information is flowing from the environment into the genome. The genome learns more about the environment, and with this information, the genome can make predictions about the state of the environment."

When asked about the origin of life, he relates one of a few hypotheses amongst scientists for the circumstances of life origins: 

"I have heard tremendous amounts of interesting stuff about what happens in volcanic vents [under the ocean]. It seems that this kind of environment is set up to get information for free. It’s always a question in the origins of life, what came first, metabolism or replication. In this case it seems you’re getting metabolism for free. Replication needs energy; you can’t do it without energy. Where does energy come from if you don’t have metabolism? It turns out that at these vents, you get metabolism for free."

 However, nothing is free. Maxwell Demon knows that. The prime denomination of that currency of information is energy. And one of the earliest components of life that transfers energy is a phosphate group in an energy unit: adenosine triphosphate (ATP). With the origin of ATP began the synthesis of large biomolecules. The release of a phosphate group supplies energy for molecular couplings, resulting in adenosine diphosphate (ADP). Subsequent combinations release a phosphate group that reattaches to ADP, forming ATP. This is a positive feedback loop that cycles over and over. 

First there was lightening. Over millions of years of trial and error a system became more stable, and it also became more adaptive. And then life was born.

We have come closer to understanding the origins of life. And I am closer to understanding how and why phosphorus evolved as the key element of life. Did Nature choose this, or did this choose Nature as it's product? That may be an ouroboros question. 

(A comment by Adami echoes thoughts throughout my higher education and academic years: "...the more you learn about different fields, the more you realize these fields aren’t separated by the boundaries people have put upon them, but in fact share enormous commonalities."  Yes.)