Book Highlight | Endless Forms Most Beautiful By Sean B. Carroll

Introduction: Evolution Of Evolutionary Developmental Biology

Darwin’s revolutionary evolution postulated a common ancestor to all living species, from which diversity evolved over billions of years. Evolution includes palaeontology (the science of fossil animals and plants). He was also aware, though clueless about the underlying mechanisms, that the embryonic stages of a wide range of animals looked remarkably similar.

Genetics is the study of the genes (the basic unit of life and discrete units on chromosomes) determining the life processes. The genes determine the production of proteins, which in turn determine the body’s organisation from a cellular to a gross level. A genome is an organism’s complete set of deoxyribonucleic acid (DNA) containing the instructions to develop and direct the organism. DNA molecules have two twisting, paired strands, each comprised of four nucleotide bases: (adenine (A), thymine (T), guanine (G), and cytosine (C)). The bases on opposite strands pair specifically (A with T, C with G). The human genome holds 3 billion of these base pairs, which reside in the 23 pairs of chromosomes within the nucleus of all our cells.

A gene, a specific part of the DNA molecule, has base pairs ranging from 1000 to 2 million (average 27,000). A gene by definition was a functional unit producing a specific protein through an intermediary RNA (DNA to RNA to protein). With discovery of genes regulating other genes, a broader definition of a gene is any discrete locus of heritable, genomic sequence affecting an organism’s traits by a functional product or by regulation of gene expression.

Embryology studies the embryos of an animal from the first cell to the completely evolved animal.  The modern synthesis was a fusion of embryology and genetics. The Third Synthesis, or Evo-Devo (short for Evolutionary Developmental biology), is the exciting branch integrating evolution with embryology at a macroscopic level and genetics at a microscopic level. Sean Carroll gives a wonderful overview of this rapidly developing field.

Animal Architecture and Common Themes

Species from a bacterium to dinosaurs evolved and diversified from a single ancestor about 600 million years back. 99% have become extinct during evolution. The amazing diversity of animal architecture, however, shows a common design plan of which modularity, symmetry, and polarity are near universal. DNA gives instructions to determine these three in an animal.

A repeating modular architecture of the vertebrate body plan has been constant over millions of years of animal evolution. Only the number and kind vary. Frogs have about 12 vertebrae; humans have 33, and snakes have a few hundred of them. Similarly, the basic five-digit design of limbs has persisted for more than 350 million years, with some variations (camels have two, rhinos have three).

The organs derived from the same ancestor are called ‘homologs’. The forelimbs of salamanders, mice, and our arms are homologs. Willinston’s law of evolution is that the parts of an organism tend toward reduction in number, with the fewer parts more specialised in function. For instance, birds’ wings are modified limbs.

Most animals exhibit bilateral symmetry, where the right and left sides mirror each other around a central axis that runs along the length of the body. Similarly, polarity has three axes: ‘head to tail’, ‘top to bottom’ (back and front in us as we stand up), and ‘near to far’ from the body (with respect to the organs projecting from the body like the limbs). The hand, for example, has three axes orientated by the thumb to the little finger, back to palm, and wrist to fingertip directions.

Monsters, Mutants, and Master Genes

Spemann, a renowned embryologist, discovered critical organising areas in embryos that directed development. In tadpoles, a specific region (the dorsal lip of the blastopore) organised the top part of the embryo into neural structures. This, in turn, initiates another embryonic axis. One way of ordering development is through interactions between different embryonic parts. These work across many scales, from the gross to microscopic.

The great mystery is how the cells in the initial undifferentiated mass migrate and differentiate into organs, tissues, and functioning cells. Studies on limb development show a well-placed system that cues cells to their final function and location. All organisers produce morphogens that influence the pattern, or morphogenesis, in tissues or cells. A major difficulty was identifying the specific morphogens in the huge chemical soup of molecules formed by the organiser cells. The study of mutants and the monsters – animals with extra organs and at wrong places (like the antenna into a leg) – finally showed ‘master genes’ at work. These genes critically determined the organisation of the embryonic cells at various levels to form the final body.

Toolkit Genes and Common Recipes

“Toolkit Genes” is one of the most exciting chapters in genetic science that explains the paradox of mice and humans having nearly identical 25,000 genes or chimps and humans having 99% identical DNA, and yet they are obviously different. Activation of specific genes in a particular manner, time, and place leads to the development, maintenance, coordination, and degeneration of the body and its parts. However, each cell has the DNA to build the entire body. How does it happen that the liver cell is only producing enzymes for digestion and not insulin?

The answer, the toolkit gene complex, are master genes activated at specific times to further activate specific genes and their products. Scientists have discovered many master genes that act at distinct levels of DNA activation and expression. Once the axes form, these toolkit genes control embryonic changes and express themselves. These toolkit genes are astoundingly exactly the same in many animals across many orders of scale preserved through almost 500 million years of evolution! The author shows how clusters of Hox genes shape the development of practically all animals, including humans.

Pax-6 genes (for forming the eye), Distal-less genes or Dll genes (for modification of the limb appendages), and Hox genes (telling where to develop heads, tails, arms, legs) are the same in every major animal group, including mice, worms, and humans. Toolkit genes are old, present in all animals and do nearly the same thing in all animals. Hence, conserved genomic material forms an important part of the molecular building blocks of life.

Evo-Devo hence proposes that evolution uses the same ingredients in all organisms but tinkers with the recipe. Animals look different not because the molecular machinery is different, but because various parts of the machinery are activated to differing degrees, at different times, in different places and in different combinations. The number of combinations is huge, and so this is a plausible explanation for the development of complex and diverse phenotypes from even a small number of genes.

A conserved genome generates novelties through rearrangements (within or between genes), changes in regulation, or genome duplication events. The combinatorial power of even a limited genetic toolkit gives it enormous potential to evolve novelties from old machinery. Humans have a mere 21,000 to 25,000 genes in the genome and yet are one of the most complex products of evolution.

Over the last decade, interest in the toolkit gene phenomenon has spread to the study of animal behaviour, too. A few key discoveries in behavioural genetics provide evidence that there may indeed be genetic tools for behaviour. In vertebrates, including humans, FoxP2 and similar genes have been repeatedly associated with speech, song, and other types of vocalisation.

Making Babies

Some animals, such as frogs and flies, undergo rapid development from the first cell, while others, like humans, develop at a more gradual pace. The cells are all the same in every place in the body. However, activation of a few genes allows the cell to reach the eye, skin, bone, or liver. How do cells migrate, and at what point of the embryo’s development is the cell’s fate sealed as belonging to only a specific tissue and organ?

Experiments have crystallised into elegant atlases of the geography and development of the embryo. Early in the development of the embryo, different axes like longitudes, latitudes, altitudes, and depths are defined clearly. The cells at specific coordinates become specific tissues and organs in a very organised manner. The geometry of the embryo’s coordinates imposes some spatial order on how the program for the toolkit gene unfolds. Toolkit gene expression takes various geometrical forms like bands, stripes, lines, spots, dots, or curves, which finally determines the animal shape and size. The toolkit’s gene logic determines the organising, subdividing, sculpting, and specifying parts of the embryo.

All vertebrate embryos, from an elephant to a human, pass through a remarkably similar looking stage. The complexity of an animal arises from the parallel and sequential action of toolkit genes. A huge symphony exists where one toolkit may activate in many places or many toolkits in one place, leading to the development of the complex animal.

The Dark Matter Of The Genome: Operating Instructions

Only 3% of our DNA is for a specific protein or a function. 97% appears functionless and is traditionally termed ‘junk’.  However, this “dark matter” of DNA plays an important role, like the dark matter in shaping the universe. Instructions for activating or silencing the toolkit genes are presented here as “genetic switches.” A genetic switch is several hundred base pairs long on average. These switches (2–3% of the dark matter) are key actors in development and evolution because they control exceptionally minute details of individual toolkit action and anatomy.

Hence, even if protein-making genes and the toolkit genes are remarkably similar in number in mice, worms, and humans, the symphony of the genetic switches makes for diversity and complexity. The switches work as GPS devices, getting a positional fix by integrating multiple inputs. The switches integrate positional information and then dictate where genes turn off and on. Tens of thousands of these switches allow an overwhelming number of combinations and permutations.

Finally, the beginning of spatial information (the two main axes) in the embryo traces back to the asymmetrically distributed molecules in the egg during its production in the ovary. The egg is indeed before the chicken, says the author. Amazingly, the asymmetrical distribution of matter in the early moments of the Big Bang gave the universe its matter distribution.

Toolkit genes are used and reused repeatedly in development in different contexts to shape the growing embryo. At least 10 switches control each toolkit gene. Feedback loops, interconnected genes, and larger circuits connecting to the smaller ones make for a huge and complex regulatory network determining the final animal architecture. Because the combination of inputs determines the output of the switch, and the potential combinations of inputs increase exponentially with each additional input, the potential output is virtually endless.

Evolution represents a significant advancement in the role of these genetic switches. Individual switches are independent information-processing units. Evolutionary changes in one switch of a toolkit gene can alter the development of one structure or pattern without altering other structures. This is the key to the evolution of modular bodies and body parts—for example, we develop an opposable thumb, and flies evolve a hindwing.

Palaeontology, Animal Evolution, and the Big Bang Of Cambrian Explosion

Palaeontology studies fossils to understand evolution. The Earth formed 4.5 billion years ago. The primitive life started relatively rapidly, between 3 and 4 billion years ago, but for 3 billion years it was small and simple. 525 to 550 million years ago, there was a sudden and rapid geological appearance of complex forms. This is the Cambrian Explosion — the Big Bang of animal evolution. Embryological studies in Evo Devo discover the role of genes in the Cambrian Explosion. The stunning discovery is that all the genes for building large, complex bodies long predated their appearance in the Cambrian Explosion by at least 50 million years.

Living organisms divide into two main groups — the prokaryotes and the eukaryotes. The latter includes all complex multicellular organisms, including animals. Insects and vertebrates are representative of the two main branches of the animal tree: protostomes and deuterostomes, respectively. Insects and vertebrates appeared first in the Cambrian Explosion period. However, we do not have any prior fossil evidence of the common ancestor of both, termed the “Urbilateria.”

Now, the basic premise is that whatever is common to two or more groups is likely to have existed in their last common ancestor. From this point of view, Evo Devo says that this Urbilateria was symmetrical on both sides and had at least six or seven Hox genes, as well as Pax-6, Distal-less, tinman, and a few hundred other genes that help build the body. It also had some light-sensing organs made up of photosensitive cells, along with projecting structures—the forerunners of limbs and fins.

The evolution of arthropods (also known as insects) and vertebrates is not attributed to an increase in genes but rather to changes in embryo geography, specifically the shifting of Hox gene zones. It is surprising that four Hox clusters have been stable throughout the evolution of amphibians, reptiles, birds, and mammals. Frogs, snakes, dinosaurs, ostriches, giraffes, and whales have evolved around a similar set of four Hox gene clusters. Thus, the evolution of two of the most successful animal groups, arthropods, and vertebrates, has been shaped by similar mechanisms of shifting Hox genes up and down the main body axis. They are variations of a common theme based on the toolkit genes, switch genes and their activation symphony.

Evo Devo has demonstrated three essential elements of early animal history. First, the last common ancestor of the two main animal tree branches was a genetically and anatomically complex animal despite an absence of fossil evidence. Second, the full genetic toolkit for bodybuilding was in place, but its potential was untapped for a long time. And third, the potential of toolkit genes is realised through the evolution of switches and gene networks and the shifting of Hox genes, starting in the Cambrian period and continuing in present times.

What finally drove the Cambrian explosion? It was an ecological phenomenon, says the author. The evolution of larger and complex animals paved the way for still larger and complex animals. The pressure of ecological interactions and competition among increasingly diverse animal species drove the evolution of higher and more complex structures — eyes for vision, hearts for circulation, and appendages for walking, swimming, and grabbing. Hence, genes in the toolkit are important actors, but they represent only possibilities, not destiny.

Evolutionary Innovation to Biodiversity

Evolutionary innovation works with what is already present. Spinnerets in spiders or wings in vertebrates did not arise de novo but are modifications of existing limbs. Nature is more of a tinkerer, cobbling together and constantly modifying available materials over millions of years. Nature is not an engineer with preconceived plans or specialised tools.

Multifunctionality and redundancy are evolutionary tricks recognised by Darwin, too. Any multifunctional structure that is partly redundant in function allows specialisation. Modular architecture consisting of repeated body parts has led to different adaptations, modifications, and specialisations of individual body parts, sometimes in the extreme, independent of other body parts.

Underlying an anatomical modularity is a modular embryo geography and a modular genetic logic of switches. These switches allow evolutionary change to occur in one part of the body independent of other structures. These switches are the secret to modularity, which in turn is the key to the evolutionary success of biodiversity.

Innovation allows for the invasion of new niches, and invasion leads to more diversity. Life started 3.5 billion years ago, but for most of that time, it was in water. Finally, due to innovations, life arrived as landforms, later adapted to high oxygen levels, developed a symbiotic relationship with plants, and there was enormous biodiversity. The basic designs remained remarkably the same across various species at the level of embryos and genes.

Butterfly Spots and Zebra Stripes

The wings of the butterfly are a modification of the limbs. The evolution of thousands of spot patterns on the wings of the butterfly is a terrific example of ‘mimicry’ in the natural world. To evade predators, tasty butterflies mimic the wing spots of noxious ones. Gene switches selectively excite and inhibit the distal-less gene, a toolkit gene, and at various stages of the butterfly’s embryonic development, resulting in the development of spots on its wings. Natural selection favours those who avoid predation.

Is the zebra a white animal with black stripes or a black animal with white stripes? The author settles for the black animal/white stripes verdict. Colouration plays a critical role in the interaction of animals with species of the same kind and others. Melanism is a condition where a species displays greater areas of dark colouration in place of other colours. Dark colouring helps moths, for example, escape bird predators when soot from industrial areas blackens the trees.

Melanin is a composite pigment of two sub-types (eumelanin and phaeomelanin) which gives the black colour to the skin. The melanin production is an interplay of many proteins and genes. An important protein, MCIR, sits on the cell membrane with one half outside the cell and one half inside. When a hormone called MSH binds to MICR, eumelanin is produced and gives black colouration. Similarly, a protein called Agouti blocks the MICR receptor and leads to the production of phaeomelanin.

The MCIR and the Agouti genes themselves are capable of many mutations leading to selective expression and inhibition of melanin production. There are many switches, too. Again, mutational changes in these switches hold the key to the diversity of melanic pigmentation in the animal kingdom.

Selection, Genes and Fitness: How Much Of An Advantage Matters

Population genetics deals with the variation of individuals, the genetic basis for it, and the role of mutations in evolution. A formula for determining the time—in generations— for a mutation to spread throughout the population is:

Time (in generations) = 2/s In(2N)

Here, N is the number of individuals in the population; “In” is the natural logarithm; and “s” is the “selection coefficient,” a measure of the relative fitness of the new mutation in terms of survival and sexual fecundity. For example, if a mutation leaves 101 offspring as compared to 100 of the non-mutational species, the “s” becomes 1% or 0.01. With s=0.01, N=10000, a new mutation would completely take over in around 2000 generations.

The powerful idea is that even with an exceedingly small advantage, a mutation spreads in a geologically brief period of time. A selection coefficient of 0.2 to 0.5, as seen in some moths, allows for huge selective advantages. Natural selection can also eliminate mutations that have a slight disadvantage.

The Making of Homo Sapiens

The difference between the minds of animals and humans is of degree, not kind. The stand of Darwin has not changed with advances in science and genetics. What makes us different? Hominids refer to both humans and apes of African origin; hominins refer to only humans until they split from the common ancestor 6 million years back. Humans today belong to the Homo sapiens line of the hominins, which includes between 15 and 20 discovered species, including Homo neanderthalensis. We have only been around for about 200,000 years. The characteristics of H. sapiens are larger body size, larger brains, longer legs relative to the torso, and smaller teeth. The hominins distinguish themselves from chimpanzees through their bipedal locomotion, upright skull on vertebral column, reduced body hair, s-shaped spine, and pelvic dimensions.

Our species are neither the last nor the best. Interestingly, Neanderthals had larger body and brain sizes than Homo sapiens. They split from a common ancestor and may or may not have interbred (the author takes the latter position). 300,000 years ago, Neanderthals died, leaving us alone as the most intelligent left on the planet. Neanderthals also used tools, made fire, and had other signs of culture, language, and self-awareness.

Absolute brain size is not necessarily an indicator of greater power. Whales and elephants have larger brains than humans, but the difference lies in the brain weight as a percentage of body weight. Thus, the human brain is 15–20 times larger than that of animals. One of the strongest reasons for higher relative brain weight could be adaptation to climactic change as the planet got colder.  

Paradoxically, humans share 98.8% of DNA bases with chimpanzees, and 99% of human genes have a mouse counterpart. Our protein-coding genes are only 20,000 to 30,000 in number, which is the same as many animals, including the roundworms. How does human complexity and domination emerge? Speech and language especially are the most vitally responsible for human evolutionary domination. The author says that complexity is not the number of genes or the proteins they encode but arises because of changes in gene control.

For example, inactivation of a protein called MHY16 is associated with reduction of the temporalis or jaw muscle in hominids. This, in turn, would reduce the stress on the bones in the skull, allowing the braincase to become thinner and larger. The brain can then grow bigger. Similarly, mutations in the FOXP2 gene or the genes controlling it in Homo sapiens could have allowed speech to flourish. These are merely fragments of the larger picture.

The author says that hominin evolution is caused by selection for different versions of many genes. This is what causes small changes in size, shape, and tissue composition to happen over many thousands of generations. To make things even more complicated, each person’s brain has a different “microanatomical structure.” This includes how the different parts of the cortex are connected, how the local wiring circuits are built, and how the neurones are arranged in the cortex. This could be the defining reason for our domination today.

Endless Forms Most Beautiful

Evo Devo, by integrating embryology, molecular genetics, and palaeontology, has led to key discoveries and provides a better method of teaching evolutionary principles. A more comprehensive understanding can have significant implications for the future of various forms of life, including humans. The author, in his final chapters says that Evo Devo, a cornerstone of modern synthesis, explains well the key principles of evolution. It suggests that the genetic mechanisms used to build the animal kingdom are ancient, which supports the concept of descent with modification.

The large-scale trends in animal design and evolution are enabled by various switches embedded in the non-coding area of the genome – the ‘dark matter’ of the genome. This process leads to complexity and diversity. Selective activation and deactivation of existing genes and structures (and not their number) contribute significantly to novelty and innovation. A handful of conserved toolkit genes, which have been present for over 500 million years, are responsible for changes at both the macro and micro levels. The most compelling message of Evo Devo is that the small-scale individual changes and the large-scale changes have the same underlying mechanism.

Teaching Of Evolution

A survey of 21 countries to review the public understanding of evolution consisted of this question:

Human beings developed from an earlier species of animals. In your opinion, how true is this argument using a four-point scale?:
1- definitely true
2- probably true
3- probably not true
4- definitely not true

East Germany scored best with a mean score of 1.86. Great Britain (2.18) and Canada (2.45) followed, and the United States (3.22) stood at the bottom. The author ruefully notes that the US now can only move upwards in the score.

The National Science Board in 1996 survey question was, “Is it true or false that the earliest humans lived at the same time as the dinosaurs?” 48% said no, 32% said yes, and 20% did not know. The author is disturbed at the public ignorance of one of the most established tenets of scientific discipline in the wealthiest, most powerful, and technologically driven nation. The author believes that this “scandal of ignorance” is comparable to not understanding the principles of the Constitution. The author feels that the visual nature of the Evo Devo perspective along with the linkage of genetics to fossil studies may greatly improve the public understanding of evolution. Evolution is the foundation of the entire discipline of biology.

Creationists and “intelligent design” groups have interfered with the teaching of biology. The Church is finally taking positions of acceptance, but the author cautions that science and evolution are best promoted by scientific knowledge and education and not by attacking religion. Similarly, religion would do better to promote its theologies and teachings rather than to attack scientific views. Classically, religion looks at the gaps in science’s understanding and promotes them as evidence of God—the “god of gaps.” However, as the gaps in understanding close down with the scientific method, the religious fundamentalists have less space to wiggle. The author is firm that nothing of intelligent design should ever be in the teaching curriculum.

The Final Stakes

The human population, 10 million before agriculture started, reached 300 million by the first century of the common era. It was 1 billion in 1800; it is currently around 8 billion and is expected to hit 9 billion in the next fifty years. In just 10,000 years, a mere blip on geological time scales, human populations have surged by a thousand-fold, yet they have profoundly influenced all life on Earth. Animal species are disappearing at an alarming rate, potentially entering the sixth mass extinction phase. The last mass extinction occurred 65 million years ago, when meteorites and natural disasters wiped out dinosaurs.

The author says that the present extinction is solely because of human activity and the persistent drive for mastery over nature. Humans believe that nature does not need our harmony and that Earth, and its species only serve us. Such an attitude does not augur well for the long-term survival of the planet and its endless beautiful species. Ultimately, our actions could lead to widespread consequences for all species, including humans. Understanding Evo Devo and appreciating the diversity and richness of the living kingdom may help us in protecting and cherishing nature.

Concluding Remarks: The Dhārmika Perspective

This is one of the most fascinating books on evolution and a must-read for all. However, there are a few striking points relevant to the Indian Sanātani or dhārmika perspective. Briefly, Western science equates religion with only the Abrahamic religions. Without discussing whether Hinduism really falls under the category of “religion,” the facts are that Hindu thought and darśanas (philosophies) never had any issues with evolution.

During the last decade of the 19th century, when Darwinism was stirring up various controversies, Swami Vivekananda was surprised at the debate and wrote that for Hindu thought, evolution is a given.

He spoke about the involution of Brahman (or Sat-Cit-Ānanda) into matter and the evolution of matter to reach Brahman as two aspects of this process.

Śrī Aurobindo developed the thesis of involution and evolution in a more detailed manner. There was nothing to argue against evolution; one must also consider the concept of involution. This would make evolution a beautiful process going towards a certain goal. The main idea put forth by Darwin was that evolution is a random and aimless process. However, recent authors (Evolution in Four Dimensions) suggest that evolution may have direction after the mind reaches a certain stage of development. Śrī Aurobindo specifically discussed the direction and purpose of evolution once the mind forms out of matter during its upward ascent. For him, the mind was still imperfect, and there were realms of Supermind and finally Sat-Cit-Ānanda to further evolve into.

Indian Knowledge Systems had a giant output in varied domains of arts, science, medicine, and engineering. It may not have explicitly talked about evolution in Darwinian terms, unlike the clearly articulated concepts in astronomy, mathematics, and physics. However, when evolution became a raging issue in the West and a fight between rationalism and science on the one hand and the Church on the other, Indian knowledge systems or its priests (Brāhmaṇas or otherwise) hardly reacted or found it problematic to accept. The issue did ruffle any feathers within the “secular” or “religious” domains.

Hinduism always deifies nature (along with the feminine, too). This belief is a striking contradiction to Abrahamic thought and Western science, which places humans at the top of the evolutionary hierarchy.

Hindu thought places the humans in harmony with nature.

The teaching of evolution has never been problematic in the Indian context. Hence, many of the problems of human nature and the poor understanding of nature and evolution are specific to the Abrahamic world rather than to the dhārmika world of India. All the same, these few remarks do not take anything away from the book itself, one of the finest examples of science writing.