November 7, 1840 (a Saturday)

On this date, the Russian founder of comparative embryology and experimental histology Aleksandr Onufriyevich Kovalevsky was born. He was the first to establish that there was a common pattern in the embryological development of all multicellular animals.

Kovalevsky began by studying the lancelet, a fish-shaped sea animal about 2-in. (5-cm) long; he then wrote Development of Amphioxus lanceolatus (1865). In 1866, he demonstrated the similarity between Amphioxus and the larval stages of tunicates and established the chordate status of the tunicates. In 1867, Kovalevsky extended the germ layer concept of Christian Heinrich Pander and Karl Ernst von Baer to include the invertebrates, such as the ascidians, establishing an important embryologic unity in the animal kingdom. This was important evidence of the evolution of living organisms. In the Descent of Man (1871), Darwin took serious note of Kovalevsky’s interpretation of the embryonic development of ascidians, writing:

M. Kovalevsky has lately observed that the larvae of the Ascidians are related to the Vertebrata in their manner of development, in the relative position of the nervous system and in possessing a structure closely like the chorda dorsalis of vertebrate animals; and in this he has since been confirmed by Prof. Kupffer. M. Kovalevsky writes to me from Naples, that he has now carried these observations further; and, should his results be well established, the whole will form a discovery of the greatest importance. Thus if we may rely on embryology, ever the safest guide in classification, it seems that we have at last gained a clew in the source whence the vertebrates were derived. I should then be justified in believing that at an extremely remote period a group of animals existed, resembling in many respects the larvae of our present ascidians, which diverged into two great branches – the one retrograding in development and producing the present class of Ascidians, the other rising to the crown and summit of the animal kingdom by giving birth to the Vertebrata.

Kovalevsky was elected to the Russian Academy of Sciences in 1890.

November 5, 1892 (a Saturday)

On this date, British geneticist and biometrician John Burdon Sanderson Haldane was born. He was one of the three major figures to develop the mathematical theory of population genetics. (He is usually regarded as the third of these in importance, after R. A. Fisher and Sewall Wright.) Population genetics became one of the key elements of what would be called the Modern Synthesis. It revealed how mutations arise and, if they are favored by natural selection, can spread through a population, causing evolutionary change without the help of imaginary Lamarckian forces. Haldane also worked in biochemistry, and on the effects of diving on human physiology. He was the first to suggest that membranes played a role in the origin of life in his prescient note in The Rationalist Annual (1926). He wrote that “The cell consists of numerous half-living chemical molecules suspended in water and enclosed in an oily film. When the whole sea was a vast chemical laboratory the conditions for the formation of such films must have been relatively favorable . . .” In 1954, Haldane, speaking at the Symposium on the Origin of Life, suggested that an alternative biochemistry could be conceived in which water was replaced as a solvent by liquid ammonia.

J.B.S. Haldane began studying science at the age of eight, as assistant to his father (the noted physiologist John Scott Haldane). A Marxist from the 1930s, Haldane was well known for his outspoken Marxist views. He resigned from the Communist Party around 1950 on the issue of Lysenko’s claims to have manipulated the genetic structure of plants and “Stalin’s interference with science.” He became known to a large public as a witty popularizer of science with such works as Daedalus (1924), Possible Worlds (1927), and The Causes of Evolution (1932).

Purportedly, it is Haldane who made the famous comment that all that biology tells us about the nature of God is that he has “an inordinate fondness for beetles” (reported in G. E. Hutchison, 1959, Amer. Natur. 93:145-159).

References:

• J.B.S. Haldane, “The Origin of Life,” The Rationalist Annual 148: 3-10 (1929).

November 4, 1855 (a Sunday)

On this date, the botanist Frederick Orpen Bower was born in Ripon, England. His study of primitive land plants, especially the ferns, contributed greatly to a modern emphasis on the study of the origins and evolutionary development of these plants. A man who did not shy away from theorizing, one of his most productive “working hypotheses” was his application of the alternation of generations model to explaining the way the land was colonized by early plants. This subject was explored most completely in his book entitled The Origin of a Land Flora: A Theory Based upon the Facts of Alternation, published in 1908.

From his many years studying liverworts, mosses, and ferns, Bower concluded that they had evolved from algal ancestors. Bower’s hypothesis states, in essence, that the sporophyte generation (the conspicuous vegetative stage in familiar vascular plants) developed de novo from a haploid alga that lacked a diploid sporophyte generation but instead had merely a diploid zygote (a cell formed by the fusion of two gametes, such as sperm and egg). Before the evolution of embryos, this zygote would have immediately undergone meiosis (to relieve the diploid condition) and produced spores, the propagules of the next haploid generation. Growth of such a spore into a gametophyte is analogous to growth of an isolated human sperm or egg cell into a hypothetical haploid generation. Thus, the sporophyte generation first appeared as an added generation that came into existence as a result of delayed zygotic meiosis – sort of a delayed plant puberty. In other words, what might otherwise have become the new haploid cells of the next generation by chromosome reduction instead retained its diploid character and thus added, aà la Bower, a new generation to the life cycle. The final step of spore production still eventually occurred, but not until after the diploid cells had grown and developed into a new sporophyte generation, in essence an overgrown zygote.

Under Brower’s hypothesis, we suppose that, from the point of view of the gametophyte, the sporophyte generation is like a giant multicellular spore factory. For example, in Coleochaete pulvinata, a modern freshwater green alga, the surface of the mature zygote is covered by a layer of haploid cells, which form ingrowths that penetrate the zygote to provide nutrition. The protected diploid zygote in Coleochaete gives the aquatic alga advantages because many more spores can be produced from a single fertilization event than would be the case if the zygote hurried straight to meiosis and the formation of one of those four spore tetrads so common in the fossil record. Bower’s hypothesis remains to be tested, but if it is correct, the sporophyte generation (diploid cells) came to develop inside (and be protected by) the gametophyte generation (haploid cells) precisely because the arrangement ultimately benefited both generations.

An older, competing hypothesis dating back to 1874 held that the algal ancestor of embryophytes already had had alternation of two generations for a long time and was thus diplobiontic, as opposed to haplobiontic. Haplobiontic organisms, such as humans, have the gametes as the only haploid cells; diplobiontic organisms develop those haploid cells into a multicellular life stage. The diplobiontic hypothesis of 1874 is less favored now because it fails to explain how the sporophytes and gametophytes, which in modern diplobiontic green algae have no long-term physical connection, could have evolved the intimate physical connection, in both nutritional and developmental respects, shared by the haploid and diploid components of all embryophytes.

Bower’s other publications included Ferns (three volumes, published 1923-28) and Primitive Land Plants (1935). Bower was elected Fellow of the Royal Society in 1891 and was awarded the Linnean Medal in 1909, the Royal Medal in 1910, and the Darwin Medal in 1938, the latter “In recognition of his work of acknowledged distinction in the field in which Darwin himself laboured.”

October 11, 1993 (a Monday)

On this date, the Nobel Assembly at the Karolinska Institute awarded the Nobel Prize in Physiology or Medicine jointly to Richard J. Roberts and Phillip A. Sharp, who in 1977 independently discovered that individual genes could be discontinuous, that is, a given gene could exist in the genetic material not as one continuous segment of DNA but as several, well-separated segments. A gene may thus consist of several segments, usually termed exons, separated by intervening, irrelevant stretches of DNA called introns. Such “split genes” are typically found in eukaryotes but not in prokaryotes, which have very compact genomes.

Richard J. Roberts

The discovery of split genes has radically changed our view on how the genetic material has changed during the course of evolution. Previously, it was thought that only minor alterations (mutations) occur within genes, producing gradual change in the genetic material. However, now it seems likely that higher organisms, in addition to undergoing mutations, may utilize another method that changes the genetic material: rearrangement or shuffling of exons that produces proteins with new functions. This can take place through crossing-over during gamete formation. This hypothesis was bolstered by the later finding that individual exons in several cases correspond to building modules (domains) in proteins and each domain has a specific function. An exon in the gene would thus correspond to a particular subfunction in the protein, and the shuffling of exons could result in a new combination of subfunctions in a protein. This kind of genetic recombination could accelerate evolution significantly.

Phillip A. Sharp

September 25, 1866 (a Tuesday)

On this date, the American embryologist and geneticist Thomas Hunt Morgan was born in Lexington, Kentucky. At Columbia University (1904-28), he began his revolutionary genetic investigations of the fruit fly Drosophila melanogaster (1908). In 1910, he discovered a white-eyed mutant in Drosophila. At that time, it was generally assumed that chromosomes could not be the carriers of the genetic information. Initially skeptical of Gregor Mendel’s research, Morgan performed rigorous experiments eventually demonstrating that genes are linked in a series on chromosomes and are responsible for identifiable, hereditary traits. When he was awarded the Nobel Prize in Physiology or Medicine in 1933, he was the first person awarded the Prize for genetics, for demonstrating hereditary transmission mechanisms in D. melanogaster.

September 19, 1864 (a Monday)

On this date, the German botanist and geneticist Carl Erich Correns was born. He is famous for rediscovering, independently of but simultaneously with the biologists Erich Tschermak von Seysenegg and Hugo de Vries, Gregor Mendel’s historic paper outlining the principles of heredity.

In 1892, while at the University of Tübingen, Correns began to experiment with trait inheritance in plants. On January 25, 1900, he published his first paper, “G. Mendel’s Law Concerning the Behavior of the Progeny of Racial Hybrids”, in which he restated Mendel’s results and his law of segregation and law of independent assortment. Although the paper cited both Charles Darwin and Mendel, Correns did not fully recognise the relevance of genetics to Darwin’s ideas.

In attempting to determine the extent to which Mendel’s laws are valid, Correns undertook a classic study on heredity in the four-o’clock plant (Mirabilis jalapa). The blotchy leaves of these variegated plants show patches of green and white tissue, but some branches carry only green leaves and others carry only white leaves. Whether a tissue is green or white depends on whether there are green or white chloroplasts in the cytoplasm of its cells. Flowers appear on all types of branches, and Correns performed a variety of crosses.

Two features of his results were surprising. First, unlike what Mendel had observed, Correns found that there was a difference between reciprocal crosses, that is, leaf color depended greatly on which parent (i.e., flower’s branch) had which trait. Such results are normally encountered only for sex-linked genes, but Correns’ results cannot be explained by sex linkage. Secondly, the phenotype of the maternal parent was solely responsible for determining the phenotype of all progeny, that is, the phenotype of the male parent appeared to be irrelevant, making no contribution to the progeny at all! Although the white progeny plants did not live long because they lacked chlorophyll, the other types of progeny did survive and could be used in further generations of crosses. The same patterns of maternal inheritance always appeared in these subsequent generations.

Maternal inheritance can be explained if the chloroplasts are somehow genetically autonomous and furthermore, are never transmitted via the sperm. This is reasonable since the chloroplasts come exclusively from the mother in most angiosperms. In his 1909 paper, Correns established variegated leaf color as the first conclusive example of cytoplasmic inheritance (cases in which certain characteristics of the progeny are determined by factors in the cytoplasm of the female sex cell), also known as extrachromosomal or non-Mendelian inheritance.

Unfortunately, most of Correns’ work went unpublished and was destroyed in the Berlin bombings of 1945.

July 28, 1840 (a Tuesday)

On this date, the American paleontologist, herpetologist, and mammalogist Edward Drinker Cope was born. Cope was a scientist by self-study and personal nature — he held no degrees except honorary ones from Haverford College and, late in life, from the University of Munich. He made many important dinosaur discoveries in western North America but spent 20 years in a protracted battle with his archrival, O.C. Marsh, for professional prestige in what came to be known as the Great Bone Wars. Financially ruined in his later years, Cope had to sell his house and move in with his museum collections. He spent his final days on a cot surrounded by piles of bones.

Cope accepted the fact of evolution but thought that change in developmental (embryonic) timing, not natural selection, was the explanation for evolution. That is, a new developmental stage would be tacked onto the end of the developmental process, pushing the old end stage further back in development. Such was the view of the American school of self-proclaimed “neo-Lamarckians,” who invoked an internal drive for “accelerated growth” as well as Lamarckian inheritance of acquired characteristics to account for the seemingly linear pattern of biological evolution that they detected in specimens from the rich fossil beds of the American West. That is, new developmental stages would cause some body parts to become very well developed if those body parts were in heavy use. Thus, the “neo-Lamarckians” thought that variation and speciation were due to changes in timing of development in different organ systems due to use.

July 20, 1822 (a Saturday)

The earliest known photograph of Gregor Mendel.

On this date, Gregor Johann Mendel was born (the day he was baptized, July 22nd, is often given erroneously as his birthday). He performed a series of beautifully designed experiments on pea plants over a period of seven years, from 1856 to 1863, to discover the principles of heredity. His studies were the first to focus on the numerical relationships among traits appearing in the progeny of hybrids; and his interpretation, clear and concise, was based on material hereditary elements that undergo segregation and independent assortment. Mendel delivered two lectures on the results of his experiments at the meetings of the Society of Natural Sciences in Brünn, Austria on February 8th and March 8th in 1865. He turned these lectures into a (long) paper, published in the 1866 issue of the Proceedings of the Society, but it received little notice. Mendel apparently even sent one of his scientific papers to Darwin, but Darwin never bothered to read it. Mendel abandoned his experiments in the 1860s after he was appointed abbot of his monastery and his time was taken up in administrative duties.

The importance of Mendel’s work was not recognized until about thirty years after the publication of his seminal paper, when Hugo de Vries in 1900 in Holland, William Bateson in 1902 in Great Britain, Franz Correns in 1900 in Germany, and Erich Tschermak in 1901 in Austria were all to acknowledge Mendel’s legacy, and hail him as the true “father” of classical genetics.

July 5, 1904 (a Tuesday)

Evolutionary biologist Ernst Mayr.

On this date, the American biologist Ernst Mayr was born in Germany. He began bird watching as a young boy, and by the age of ten, he could recognize all of the local bird species by call as well as sight. Mayr was known for his work in avian taxonomy, population genetics, and evolution. He led development of what has become known as the “modern synthesis,” the establishment of Darwin’s theory of evolution on a firm foundation of experimental genetics and population statistics. In 1940, Mayr proposed the concept of a species as a group of populations that are reproductively isolated from other such groups, the definition most widely used by biologists today.

Mayr was productive throughout his life and lived to a ripe old age but could never fully explain his longevity. “There is no history of it among my ancestors and both my parents died of cancer,” he said. “Probably it results from exercising every day, living a healthy life and having an active mind. My mind is still in very good shape; I have never let it rest. I’ve always had a tremendous breadth of interest; I’ve always wanted to know everything and read everything.” He died on February 3, 2005.

May 27, 1961 (a Saturday)

On this date, in a laboratory on the seventh floor of Building 10 on the NIH campus in Bethesda, Maryland at three o’clock in the morning, J. Heinrich Matthaei combined the synthetic RNA made only of uracil (called poly-U) with cell sap derived from E. coli bacteria and added it to each of 20 test tubes. This time the “hot” test tube was phenylalanine. The results were spectacular and simple at the same time: after an hour, the control tubes showed a background level of 70 counts, whereas the hot tube showed 38,000 counts per milligram of protein. The experiment showed that a chain of the repeating bases uracil forced a protein chain made of one repeating amino acid, phenylalanine. The genetic code could be broken! UUU=Phenylalaline was a breakthrough experimental result for Marshall Nirenberg and Heinrich Matthaei.  In August 1961, they published their now-classic essay, “The Dependence of Cell-Free Protein Synthesis in E. Coli upon Naturally Occurring or Synthetic Polyribonucleotides,” in the Proceedings of the National Academy of Sciences.

April 25, 1953 (a Saturday)

On this date, James Watson and Francis Crick published an article in the journal Nature describing the structure of DNA in terms of the now-familiar double helix. Watson was working at the Cavendish Laboratory, University of Cambridge, in early October 1952. He met Francis Crick there and they agreed that, working together, they should be able to discover the structure of DNA that had eluded others. Crick brought to the project his knowledge of x-ray diffraction, while Watson brought knowledge of phage and bacterial genetics. In April 1953 they jointly published their theory, complete with a diagram of “two helical chains coiled round the same axis.” Watson (age 25 at the time), was born in Chicago; Crick (age 36 at the time), was born in Northampton, England. Their discovery won them both, with Maurice Wilkins, the Nobel Prize in Physiology or Medicine in 1962.

Human Genome Project director Francis Collins says, even 50 years later, it’s impossible to overstate the importance of knowing the structure of DNA:

It is so intertwined in every bit of what we do experimentally, in terms of perceiving our own position in the scheme of life on this planet. It has become one of those givens that is so central to your thinking that you stop thinking about it, but if somebody took it away from you, your whole intellectual foundation would collapse, and it would be unimaginable what we would be doing now if we didn’t know about the double helix.

Furthermore, DNA is not just an instruction book for the present and something to pass on to future generations – it is also record of our genetic past. No longer do researchers look for clues to human history merely in fossil bones and stone tools, they also seek “genetic fossils” in the DNA of living peoples.

April 1, 1578

On this date, the English physician and scientist William Harvey was born. He is credited with being the first in the Western world to describe correctly and in exact detail the systemic circulation and properties of blood being pumped around the body by the heart. Harvey published his discovery in a treatise entitled Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (On the Motion of the Heart and Blood in Animals) in 1628. His discovery was dramatically confirmed later in the seventeenth century by microscopist Marcello Malpighi’s discovery of capillaries.

Functional knowledge of the heart and the circulation had remained almost at a standstill ever since the time of the Greco-Roman physician Galen – 1,400 years earlier. With Harvey, life began to receive mechanistic explanation. The essential idea of mechanistic explanation is that “natural” events have “natural” causes and can be explained by cause-and-effect relationships that do not involve special action of supernatural agency. This is fundamental to modern science.

In Exercitationes de Generatione Animalium (On the Generation of Animals) in 1651, Harvey was extremely skeptical of spontaneous generation and proposed that every living animal originally comes from an egg, introducing the oft-quoted phrase “ex ova omnia” (all [life] from eggs). [However, Harvey did not completely reject spontaneous generation.] His experiments with chick embryos supported the theory of epigenesis, which states that organisms develop from substances in the egg that differentiate during embryonic development.  This was in conflict with the now-descredited preformationist view that perfect miniature versions of offspring exist in the gametes and grow during development.  [Please note that the term 'epigenesis' carries different meanings. Here, it used used in the older sense, as a theory of animal and plant development. In more modern times, it refers to mechanisms by which gene regulation over generations is controlled by elements other than DNA.]

February 17, 1890 (a Monday)

On this date, the English geneticist Ronald Aylmer Fisher was born. His book The Genetical Theory of Natural Selection (1930), with its ground-breaking treatment of the concepts of fitness and dominance, was a milestone work in that field.

February 16, 1834 (a Sunday)

On this date, the German biologist, naturalist, philosopher, physician, and artist Ernst Heinrich Philipp August Haeckel was born at Potsdam. He abandoned his medical practice after reading Charles Darwin’s The Origin of Species in 1859 and returned to school, studying zoology and anatomy and eventually earning a position as professor in Jena.

Haeckel embraced the pre-Darwinian notion that life formed a series of successively higher forms, with embryos of higher forms “recapitulating” the lower ones. He thought that, over the course of time, evolution added new stages to produce new life forms. Thus, embryonic development was actually a record of evolutionary history. The single cell corresponded to amoeba-like ancestors, developing eventually into a sea squirt, a fish, and so on. Haeckel, who was very good at packaging and promoting his ideas, coined both a name for the process – “the Biogenetic Law” – as well as a catchy motto: “Ontogeny recapitulates phylogeny.” Haeckel was so convinced of his Biogenetic Law that he was willing to bend evidence to support it. The truth is that the development of embryos does not fit into the strict progression that Haeckel claimed, but it has also been shown that ontogeny (development of a fertilized ovum through to maturity) and phylogeny (development of a species over time) are closely related. Interestingly, Haeckel was one of the first to create a phylogenetic tree, which was designed to show the evolutionary relationships among various species and was also very advanced for its time.

Although a strong supporter and defender of evolution (especially against attacks from religious leaders), Haeckel was not a Darwinian since he did not accept natural selection as an explantion for how evolution proceeds. Instead, he favored a type of Lamarkism, by which parents acquire physical characteristics during their lifetime and pass them along to their offspring.

Much later, Haeckel attempted to develop a comprehensive philosophical system informed by biological and evolutionary findings. This system was to encompass ethics, theology, psychology and politics – indeed, he is quoted as having said that “politics is applied biology.” Unfortunately, some of that work was later appropriated by the Nazis who used it as justification for their racism and nationalism.

Haeckel’s major works are The History of Creation (1868 ) and The Riddle of the Universe (1899).

February 7, 1877 (a Wednesday)

On this date, the English mathematician Godfrey Harold Hardy was born. Although Hardy considered himself a pure mathematician, early in his career, he nevertheless worked in applied mathematics when he formulated a law that describes how proportions of dominant and recessive genetic traits will propagate in a large population (1908). Hardy considered it unimportant but it has proved of major importance in population genetics and evolutionary biology. Ironically, in his book entitled A Mathematician’s Apology (1940), he wrote:

I have never done anything ‘useful’. No discovery of mine has made, or is likely to make, directly or indirectly, for good or ill, the least difference to the amenity of the world.

As it was also independently discovered by Wilhelm Weinberg, it is known as the Hardy-Weinberg principle.

Hardy–Weinberg principle for two alleles: the horizontal axis shows the two allele frequencies p and q, the vertical axis shows the genotype frequencies and the three possible genotypes are represented by the different glyphs.

February 3, 1857 (a Tuesday)

On this date, the Danish botanist and geneticist Wilhelm Ludvig Johannsen was born. His experiments in plant heredity offered strong support to the mutation theory of the Dutch botanist Hugo de Vries (that changes in heredity come about through sudden, discrete changes of the heredity units in germ cells). Many geneticists thought Johannsen’s ideas dealt a severe blow to Charles Darwin’s theory that new species were produced by the slow process of natural selection.

Johannsen explained his ideas in his book entitled On Heredity and Variation (1896), which he revised and lengthened with the rediscovery of Gregor Mendel’s laws and reissued as The Elements of Heredity in 1905. The enlarged German edition of this work was published in 1909 and became the most influential book on genetics in Europe. In it, Johannsen coined the terms “gene”, “phenotype”, and “genotype”.

January 17, 1834 (a Friday)

On this date, the German biologist August (Friedrich Leopold) Weismann was born in Frankfurt. Ernst Mayr ranked him the second most notable evolutionary theorist of the 19th century, after Charles Darwin. Weismann was one of the founders of modern genetics, who is best known for his opposition to the concept of the inheritance of acquired traits and for his “germ plasm” theory, the forerunner of DNA theory.

In 1885, Weismann suggested that hereditary characteristics were transmitted by what he called germ plasm – as distinguished from the somatoplasm (body cells) – which linked the generations by a continuous stream of dividing germ cells. In stating definitely seven years later that the material of heredity was in the chromosomes, Weismann anticipated the chromosomal basis of inheritance.

December 21, 1889 (a Saturday)

On this date, the American mathematician and biologist Sewell Green Wright was born. He was one of the founders, along with R. A. Fisher and J. B. S. Haldane, of modern theoretical population genetics. He researched the effects of inbreeding and crossbreeding with guinea pigs and, later on, the effects of gene action on inherited characteristics. The synthetic theory of evolution as described by Sewell Wright attempts to explain evolution in terms of changes in gene frequencies.

The classic example which supports this theory is that of the peppered moth in England. The moth can be either dark or light colored. Scientists have determined that body color in the peppered moth is controlled by a single gene with two alleles: the allele for dark body color is dominant and the allele for light body color is recessive. Prior to the industrialization of central England, the light-colored allele was most prevalent. The light-colored moths would hide on the white-barked trees and avoid bird predation. But the pollution generated by the new industries stained the light-colored trees dark. Gradually the light-colored moth was attacked and that allele became much less prevalent. In its place, the dark-colored allele became the most predominant allele because moths that carried that allele could camouflage themselves on the stained trees and avoid being eaten by their bird predators. Clearly the population had evolved to a higher adaptive condition.

Wright is perhaps best known for his concept of genetic drift, formerly known as the “Sewell Wright effect.” Genetic drift results when small populations of a species are isolated and due to pure chance, the few individuals who carry certain relatively rare genes may fail to transmit them. The genes may therefore disappear and their loss may lead to the emergence of new species, although natural selection has played no part in the process. Genetic drift can be summarized as “bad luck, not bad genes.”

What’s a cell-adhesion protein like you doing in a unicellular organism like me?

The principle of common descent in evolutionary theory means that all living organisms are related to each other in a genealogical sense. In other words, many of the similarities between different organisms exist because they were inherited from a common ancestor with those features. Since inherited traits are encoded in the DNA of the organisms, comparisons of their genes is a way to infer descent from a common ancestor.

One of the similarities among all metazoans is their multicellularity, which requires proteins that enable cells to adhere and communicate. A number of cell adhesion and cell-cell signaling proteins do this in multicellular organisms, but only such proteins that exist in all (or nearly all) modern metazoans, but not in any other multicellular organisms such as fungi and plants, should have been present in the last common ancestor (LCA) of metazoans. The cadherin family of proteins apparently meets this criteria.

Cadherins have also been found in the choanoflagellates, which are unicellular and sometimes colony-forming organisms. Each cell has a single flagellum surrounded by a collar (choano comes from the Greek word for collar) of microvilli that it uses to swim and capture bacterial prey. As the flagellum beats, it draws water through the collar’s microvilli, which filter out bacteria and other tiny food particles. Choanoflagellates are nearly indistinguishable, in terms of shape and function, from the “collar cells” (choanocytes) of sponges, the simplest metazoans. The beating flagella of choanocytes generate a current that draws water and food particles through the body of the sponge, and their microvilli filter out food particles. Henry James-Clark first recognized this remarkable similarity over 130 years ago, which eventually led to the hypothesis that sponges, and, by implication, other animals, evolved from choanoflagellate-like ancestors.

To investigate this possibility, Abedin and King first examined the published genomes of a choanoflagellate, Monosiga brevicollis, and four diverse animals to identify cadherin genes in each. Surprisingly, despite the lack of obvious cell adhesion in M. brevicollis, its number of putative cadherin genes (23) is greater than the number of recognized cadherin genes in the fruitfly Drosophila melanogaster (17). Of the other animals they looked at, the mouse Mus musculus has the most cadherin genes (127), followed by the sea anemone Nematostella vectensis (46), and the sea squirt Ciona intestinalis (32). When compared as a percentage of the total number of genes in each genome, cadherins are more common in M. brevicollis than in any of the four metazoans except M. musculus.

The cadherin repeat is a repeating domain (functional subunit of a protein) found in all cadherin proteins, which enables them to adhere to each other and which depends on calcium ions (Ca⁺²) to function (cadherins are named after it). A cadherin protein typically consists of an extracellular region, a single membrane-spanning region, and a cytoplasmic region. The cadherin repeat is found in the extracellular region; surprisingly, in comparing the five organisms, Abedin and King discovered that the average number of extracellular cadherin repeats (ECs) in M. brevicollis is highest (14.7), while the average in M. musculus is lowest (5.2).

In the extracellular and cytoplasmic regions of different cadherin proteins, other distinctive domains can be found. The extracellular domains EGF and LamG are shared by M. Brevicollis, N. vectensis, and M. musculus, while the extracellular domains N-hh and IG and the cytoplasmic domain SH2 are shared by M. brevicollis and N. vectensis. This suggests that these domains were present in the LCA of choanoflagellates and metazoans. A cytoplasmic domain called the classic cytoplasmic domain (CCD) is responsible for the ability of classic cadherin proteins (defined as those involved in cell-cell adherens junctions) to anchor, with the help of catenins, to the actin cytoskeleton. As a result, the actin cytoskeleton of one cell can be linked to the cadherins in the plasma membrane, which in turn attach through their extracellular regions to the cadherins in the neighboring cell membranes. However, since CCDs are found in N. vectensis and M. musculus but not in M. brevicollis, the CCD-containing cadherins probably evolved after the origin of the metazoans.

Given that Monosiga brevicollis leads a unicellular lifestyle and is not known to form cell-cell contacts, what are its putative cadherins doing? In an effort to answer this question, Abedin and King determined the locations in choanoflagellate cells of two nearly identical cadherin proteins, MBCDH1 and MBCDH2. Both of them resemble the inferred ancestral cadherin in having SH2 domains but not CCDs. The locations of polymerized actin in the cells were also determined. The experiments showed that actin, MBCDH1, and MBCDH2 proteins were localized together around the base of the choanoflagellate cell, where the choanoflagellate attaches to surfaces, and especially around the microvilli of the collar, where bacteria are captured and ingested. This implies that the associations between cadherins and actin filaments was present in the LCA of choanoflagellates and metazoans. But why?

The localization of these ancient cadherin proteins suggests that perhaps the choanoflagellate/metazoan LCA used them to bind and eat bacteria, while the multicellular metazoans adopted these proteins for gluing their cells together. Abedin and King support this hypothesis by pointing out that some pathogenic bacteria today bind to the extracellular region of metazoan cadherins, taking advantage of them to help invade the host cell. “Indeed, the transition to multicellularity likely rested on the co-option of diverse transmembrane and secreted proteins to new functions in intercellular signaling and adhesion,” they conclude in their report.

References:

• Abedin, M., King, N. (2008). The Premetazoan Ancestry of Cadherins. Science, 319(5865), 946-948. DOI: 10.1126/science.1151084
• King, N. (2004). The Unicellular Ancestry of Animal Development. Developmental Cell, 7(3), 313-325. DOI: 10.1016/j.devcel.2004.08.010
• Snell, E. (2001). Hsp70 sequences indicate that choanoflagellates are closely related to animals. Current Biology, 11(12), 967-970. DOI: 10.1016/S0960-9822(01)00275-5
• University of California – Berkeley. “Genome Of Marine Organism Tells Of Humans’ Unicellular Ancestors.” ScienceDaily 20 February 2008. 31 March 2008 .