Here I describe a scenario that explains how life could have originated through molecular coevolution. When the Earth was warm, organic matter partitioned into an oil slick on the ocean’s surface, an aqueous layer with low concentrations of soluble organic substances and a benthic “kerogen” layer. The interface between the oil slick and the aqueous layer is proposed to be where life began. The overlying oil slick could generate complex monomers and polymers through dehydration reactions and photochemistry. The interface between polar and hydrophobic layers would be enriched with amphiphiles that could retain biologically important molecules at the site. Environmental cycles of suitable periodicity could entrain nucleic acid replication. Peptides enriched with arginine play a pivotal role. They aggregate nucleic acids (NA), preventing dispersal and aiding replication and elongation. Furthermore, arginine’s guanidium group forms high-energy phosphate bonds able to catalyze energy transfer during NA replication and peptide synthesis. Thus, families of NAs that helped incorporate arginine into peptides comprise the core of the first living system. A specific candidate is proposed for the protobiont, based on an autocomplementary NA sequence that bears arginine’s codon and anticodon and demonstrates stereospecific affinity for this amino acid. The relationship between arginine and these NA strands represents the first step in the genetic code’s evolution. Subsequent elaboration of the code occurred through molecular coevolution, natural selection favoring the retention, and replication of NA that helped make peptides with properties useful to evolving biological systems. Early in biological evolution, there were no barriers to the free exchange of nucleic acids. Thus genetic combinations that functioned cooperatively would have easily formed, increased through natural selection, and spread throughout a global set of interactive “composomes” near the ocean’s surface.

Among various scenarios that attempt to explain how life arose, the RNA world is currently the most widely accepted scientific hypothesis among biologists. However, the RNA world is logistically implausible and doesn’t explain how translation arose and DNA became incorporated into living systems. Here I propose an alternative hypothesis for life’s origin based on cooperation between simple nucleic acids, peptides and lipids. Organic matter that accumulated on the prebiotic Earth segregated into phases in the ocean based on density and solubility. Synthesis of complex organic monomers and polymerization reactions occurred within a surface hydrophilic layer and at its aqueous and atmospheric interfaces. Replication of nucleic acids and translation of peptides began at the emulsified interface between hydrophobic and aqueous layers. At the core of the protobiont was a family of short nucleic acids bearing arginine’s codon and anticodon that added this amino acid to pre-formed peptides. In turn, the survival and replication of nucleic acid was aided by the peptides. The arginine-enriched peptides served to sequester and transfer phosphate bond energy and acted as cohesive agents, aggregating nucleic acids and keeping them at the interface.

Abel, Daniel C., 67 Aronson, Richard B., 303 Atchison, Gary J., 11 Berkman, Hilary E., 285 Bodkin, James L., 73 Britton, Robert H., 109 Bugaev, Victor F., 241 Cole, Kathleen S., 235 Coutant, Charles C., 161 Crivelli, Alain J., 109 Danzmann, Roy G., 249 Davis, Will iam P., 67 Degani, Gad, 149 Dewees, Christopher M., 313 Duthie, Garry G., 309 Ferguson, Moira M., 249 Fischer, Eric A., 143 Fletcher, Garth L., 295 Golovatjuk, Galina Ju., 241 Grover, Jill, 313 Harris, Margaret A., 173 Hart, Thomas F. Jr., 41 Henry, Mary G., 11 Hlohowskyj, Ihor, 277 Hofer, Rudolf, 209 Jameson, Ronald J., 73 Jastrzebski, Zbigniew T., 66 Kao, Ming H., 295 Klimley, A. Peter, 27 Koenig, Christopher C., 67 Kramer, Donald L., 81 L’AbCe-Lund, Jan Henning, 219 Lejeune, Pierre, 135 Levanon, Dan, 149 Lyons, John, 93 Margraf, F. Joseph, 77 McDonald, Michael E., 229 McNeely, David L., 195 Meffe, Gary K., 3 Meyer, Axel, 127 Moses, Boniface S., 51 Nelson, Joseph S., 173 Quinn, Thomas P., 155 Rabeni, Charles F., 285 Reisman, Howard M., 295 Rheinberger, Veronika, 209 Sanderson, S. Laurie, 303 Sandheinrich, Mark B., 11 Savvaitova, Ksenia A., 241 Schaeffer, Jeffrey S., 77 Shapiro, Douglas Y., 183 Shears, Margaret A., 295 Smith, R. Jan F., 235 Tallman, Ross F., 155 VanBlaricom, Glenn R., 73 Vollestad, Leif Asbjorn, 219 Walsh, Will iam J., 257 Werner, Robert G., 41 Wieser, Wolfgang, 209 Wissing, Thomas E., 277 Ziuganov, Valery V., 241

Journal Article The Life of the First Vertebrates: A novel hypothesis suggests that our earliest vertebrate ancestors may have spent their lives partly in fresh water and partly at sea Get access Robert W. Griffith Robert W. Griffith Search for other works by this author on: Oxford Academic Google Scholar BioScience, Volume 44, Issue 6, June 1994, Pages 408–417, https://doi.org/10.2307/1312364 Published: 01 June 1994

1. Recombinant salmon growth hormone at doses of 0.8 and 2.1 mu g/g significantly enhanced linear growth in hypophysectomized male killifish, Fundulus heteroclitus, over that of controls and a significant regression was found between growth and the logarithm of dose. 2. Bovine growth hormone elicited significant growth enhancement at all three dosages tested (1, 4 and 10 mu g/g) and a significant log/dose relationship was also observed. 3. Observations on the relative weight of the gonads indicate that whole salmon pituitary extract (25 mu g/g) possesses strong gonadotropic activity and that both bGH and rsGH had smaller but significant effects on the gonads. 4. It is suggested that growth hormone may play a subsidiary synergistic role to other pituitary hormones in gonadal development.

The question of how (and why) the ureosmotic strategy, characteristic of Latimeria chalumnae and the chondrichthians evolved is addressed. There are three requirements for ureosmotic regulation: urea synthesis via the ornithine-urea cycle, urea tolerance involving biochemical and physiological adjustments, and urea retention that requires renal, branchial, metabolic and reproductive adaptations. Several examples of lower vertebrates in which urea plays a physiological role are considered to see whether they might provide insight into the origin of ureosmotic regulation. The guppy shows high urea synthesis and retention during embryonic development, and it is possible that a developmental role of urea is a general phenomenon in fishes. The toadfish, thought to be an enigma with high urea synthesis in the absence of an obvious physiological role of urea, is ureotelic under some conditions. Its urea excretion is likely related to renal function and/or parental care. In lungfish high ureogenesis is associated with estivation in periodically dry habitats. The resultant hyperuremia prevents ammonia toxicity, inhibits water loss and may repress metabolism. Latimeria is a classic marine ureosmotic regulator in which urea is used as an osmolyte that allows osmotic equilibrium with sea water while maintaining low ion levels. Adults of the frog, Rana cancrivora, are also ureosmotic regulators in brackish water. A scenario is proposed that suggests how ureosmotic regulation could have evolved in Latimeria and other fishes. The ornithine-urea cycle (composed of an arginine synthetic pathway and a second pathway that splits arginine into urea) occurred in fossil anadromous agnathans. Here the first pathway functioned in the ammocoete-like larvae for the generation of arginine to supplement a protein-deficient diet of algae, whereas the arginase pathway was important in the embryo for vitellin catabolism. Gnathostome evolution was associated with trends towards large eggs and prolonged development, requiring a complete ornithine-urea cycle for ammonia detoxification in embryos. Retention of a complete ornithine-urea cycle throughout adult life (via paedomorphosis) would preadapt any relatively large, sluggish, euryhaline fish for ureosmotic regulation when it was exposed to sea water. It is suggested that ureosmotic regulators evolved from freshwater or anadromous ancestors that entered the marine habitat. Once early ureosmotic regulators were established in the sea there would have been strong selection for internal fertilization and development, as is seen in Latimeria and many elasmobranchs. It is suggested that ureosmotic regulation was a common strategy in Paleozoic marine gnathostomes.

The effects of recombinant salmon growth hormone (sGH) on plasma sex steroid levels and gonadal function were investigated in hypophysectomized Fundulus heteroclitus. Effects of sGH were compared to those of purified chum salmon prolactin (sPRL), Atlantic salmon gonadotropin (sGTH), and salmon pituitary extract (sPE). Treatment with sGH significantly increased plasma concentrations of testosterone in males and estradiol-17β in females; sPRL had similar effects on testosterone levels in males. Further, treatment with these hormones prevented the decline in gonadal weight observed after hypophysectomy in both males and females. In vivo treatment of male fish with sGH also augmented testosterone and 11-ketotestosterone production by testis tissue subsequently incubated in vitro. Direct action(s) on gonadal steroidogenesis was examined by incubating gonadal tissues from hypophysectomized fish in vitro with various hormones. sGH significantly stimulated the in vitro production of testosterone and 11-ketotestosterone by testis, and estradiol-17β by ovary. sPE and sGTH also stimulated gonadal steroidogenesis, whereas sPRL and bovine GH had no significant effect. By comparison, rainbow trout gonads also produced increased amounts of steroids when treated with sGH in vitro. The use of a cloned GH rules out contamination by other pituitary hormones. These results, therefore, demonstrate that recombinant salmon growth hormone possesses steroidogenic and gonadotropic activity. Purified sPRL also has steroidogenic and gonadotropic actions. However, the significance of these effects of teleost GH and PRL is not known.

1. Paleontological data indicate that the earliest recognizable vertebrate remains, bone fragments of Upper Cambrian and Lower Ordovician heterostracan fishes, were deposited in a marine situation. 2. Since these earliest fossils are sporadic in occurrence, from atypical marine deposits and since they only represent the full grown adult stage, the possibility of a freshwater developmental stage or estuarine habitat cannot be excluded. 3. The hagfishes, supposedly the most primitive of living vertebrates, are exclusively marine and possess an osmoregulatory strategy (monovalent ion levels nearly identical with sea-water with little capability of regulation) that is consonant with a strictly marine evolutionary history. Possibly, but less parsimoniously, this strategy and habitat could be secondarily derived. 4. The hagfish has a glomerular kidney, renal sodium reabsorption and branchial pumps for the uptake of sodium and chloride which are indicative, but not unequivocally diagnostic, of a freshwater ancestry. 5. A scenario in which the earliest vertebrate was anadromous, breeding in fresh water and migrating to the sea, is consistent with the paleontological data and with the physiology and life history of living 'primitive' fishes. It also leads to more coherent explanations for the origin of bone and for the evolution of vertebrate special senses than do alternative marine scenarios.

1.1. The osmotic adaptations for dehydration of the Chilean clingfish (Sicyases sanguineus) were examined in emerged fish.2.2. Plasma osmolarity, electrolyte levels, body weight changes, hematocrit, muscle water content and urea were measured at various times up to 24 hr of emersion.3.3. At 24 hr of emersion, the gut surface of the fish was reddish with engorged capillaries. The concomitant presence of air in the gut suggests a role for the intestine in the air breathing mechanism.4.4. S. sanguineus maintained out of water showed a significant loss of body weight and increases in hematocrit values and plasma osmolarity, urea and electrolyte levels.

Serum osmolarity, chloride, urea, protein, and trimethylamine oxide were measured in 15 shallow water marine teleosts, 6 elasmobranchs, 9 deep benthic teleosts, and 24 midwater teleosts. Amino acids, carbohydrates, phosphate, and hematocrits were determined for some species from these four groups. Elasmobranchs had high osmolarity (1035 mOsm/l) because of high serum urea (363 mM/l), TMAO (66 mM/l), and chloride (295 mM/l). Shallow water teleosts had low osmolarity (444 mOsm/l), chloride (176 mM/l), urea (4 mM/l), and TMAO (14 mM/l). Deep benthic teleosts had higher osmolarities and chloride levels (576 mOsm/l, 242 mM/1) than shallow water teleosts, as did midwater teleosts (561 mOsm/l, 267 mM/1). Serum TMAO was high in benthic (51 mM/l), but not midwater (12 mM/l) teleosts, and urea was low in midwater (1.0 mM/l) and benthic (1.5 mM/l) groups. Stress and morbidity raise osmolarity and chloride in marine teleosts and may account for high values in midwater and benthic fishes, which were sampled after considerable trauma. The data suggest that deep-sea teleosts osmoregulate as do shallow water species, and do not support the notion that osmoregulatory specializations, such as ureosmotic regulation, evolve more rapidly in the deep sea. Very low serum proteins (0.8 g/100 ml) and hematocrits (< 10%) in midwater teleosts possibly relate to buoyancy or low metabolism.

The coelacanth, Latimeria chalumnae , possesses a blood chemistry that is nearly identical to that of the elasmobranch fishes and contrasts with that of the bony fishes and tetrapods. Especially notable is the retention of high concentrations of urea (377 mM) and of trimethylamine oxide (122 mM), which aid in raising the blood osmolarity (942 mosm/I) to close to that of the sea water environment. These features also characterize other coelacanth body fluids, such as the notochordal fluid, aqueous and vitreous humours, ventricular fluid, coelomic fluid and bile. The tissues of Latimeria , such as muscle, are also characterized by high urea concentrations. The osmotic balance between extracellular fluids and tissues seems to be achieved by the presence of very high tissue levels of trimethylamine oxide ( ca . 300 mmol/(kg H 2 O)), which counteract the low ion concentrations found in tissue. Renal function in Latimeria seems to involve the selective elimination of certain divalent ions (magnesium, phosphate and sulphate) and of organic substances (glucuronate, creatine and some amino acids). Unlike other ureosmotic fishes, the coelacanth does not possess the renal capacity to reabsorb urea. Evidence suggests that the rectal gland, structurally much like those of chondrichthyians, functions to excrete excess sodium chloride. Since the blood osmolarity of Latimeria is some­what lower than that of sea water (942 cf. 1026 mosm/l), it is in negative water balance. Some evidence suggests that this is overcome by drinking sea water in a manner similar to that of the teleosts. The problem of whether ureosmotic regulation is homologous in Latimeria and the chondrichthyians is moot, although we favour the possibility that it was independently acquired for the following reasons. (1) Renal urea reabsorbtion is absent in Latimeria although it is crucial to ureosmotic regulation in the chondrichthyians. (2) Internal fertilization and development are necessary concomitants of ureosmotic regulation in fishes and internal fertilization in the two groups is achieved by non-homologous mechanisms. (3) Ureosmotic regulation has been evolved independently in a third vertebrate group, the euryhaline amphibian Rana cancrivora .

1.1. Killifish, Fundulus heteroclitus, were exposed to high urea concentrations at different salinities. Mortality, plasma urea and plasma sodium were determined.2.2. Following a step-wise increase in environmental urea, seawater (SW) fish die at concentrations from 0.6 to 1.0 M. At a constant 0.4 M urea concentration, higher mortality is found in fresh water (FW)than in SW or 13 SW.3.3. Plasma urea offish in 0.4 M urea is less than that of the environment and ranged from 197mM in SW to 260 mM in 13 SW after 3 days and 370 mM in SW fish after 9 days.4.4. High urea elicited changes in plasma sodium that followed the environmental gradient.5.5. Evolutionary implications of the moderately low toxicity of urea to the teleost fishes are discussed.

Osmoregulatory mechanisms were examined in major groups of fishes including hagfish, holocephalans, elasmobranchs, the coelacanth, and ray-fin fishes. Four main patterns of body fluid composition emerged. These represent the three main osmoregulatory processes in the marine environment and the one in fresh water. Some possible interrelationships among these four types are discussed. Urea retention in marine elasmobranchs and the coelacanth, although similar, may have been acquired independently during evolution. The importance of gills and the rectal gland in elasmobranch osmoregulation is discussed. The importance of amino acids in intracellular osmoregulation in elasmobranchs is also reviewed. Recent studies on water and electrolyte regulation in freshwater stingrays are summarized.

Major inorganic electrolytes and organic solutes were measured in urine obtained from the bladder of a live specimen of the coelacanth, Latimeria chalumnae, and the results were compared with data on blood serum from the same fish. Osmolarity is essentially identical in the two fluids. Magnesium, phosphate, sulfate, creatine, creatinine and glucuronate are highly concentrated in the urine whereas chloride, bicarbonate, protein and glucose are much lower in urine than in serum. There are moderately higher levels of potassium, total amino acids and total carbohydrates and somewhat lower concentrations of sodium, trimethylamine oxide and lactate in urine than in serum. Total calcium levels in urine are considerably lower than serum total calcium, but are slightly higher than the dialyzable calcium fraction of serum. Urea levels in urine and serum are identical.

1.1. Activity levels of sodium-potassium activated adenosine triphosphatase in the rectal gland of Latimeria chalumnae were found to be comparable with those in elasmobranch fish, implicating a role of the coelacanth rectal gland in salt secretion.2.2. Moderately high activities of the enzyme were also found in kidney and rostral organ of Latimeria.

Fluid from the notochordal canal of the coelacanth, Latimeria chalumnae, was analyzed for major inorganic and organic constituents and compared with blood serum from the same fish. Significantly or suggestively lower levels of sodium, magnesium, calcium, bicarbonate, sulfate, total carbohydrates, glucose, lactate, cholesterol, bound phosphate and total proteins were found in notochordal fluid than in serum, whereas potassium, chloride, urea, trimethylamine oxide, and total free amino acids were higher and inorganic phosphorus essentially identical. Osmolarity of notochordal fluid (1058 mOsm) exceeds that of serum (942 mOsm). A whitish precipitate in the fluid consisted of a matrix of fibers 100 A in diameter and of indefinite length. It resembled a sialoglycoprotein in composition and was stabilized by disulfide bonds. The fluid contained cellular debris.

Removal of the Stannius corpuscles of Fundulus heteroclitus adapted to freshwater, dilute seawater, or seawater, has little effect on serum sodium, potassium, or chloride. Injection of homogenate of Stannius corpuscles into intact or Stanniectomized fish also has no consistent effects on these electrolytes. In light of the marked effects of the operation or injection therapy on serum calcium levels, it is suggested that the physiological role of the corpuscles of Stannius is the maintenance of serum calcium and that observed minor effects on serum monovalent electrolytes are indirect ones.

AbstractInorganic and organic constituents were studied on blood serum collected from a living specimen of the coelacanth, Latimeria chalumnae. Inorganic electrolytes determined included sodium (196.7 mM/l), potassium (5.78 mM/l), magnesium (5.30 mM/l), calcium (4.94 mM/l), chloride (186.7 mM/l), bicarbonate (9.60 mM/l), phosphate (5.08 mM/l), and sulfate (4.80 mM/l). Serum urea (377 mM/l) and trimethylamine oxide (122 mM/l) were high as previously reported, and accounted for the bulk of the total non‐protein nitrogen (1199 mg%); total amino acids added a small but not insignificant fraction (21.9 mg%). High serum lactate (16.5 mM/l) and glucose (6.57 mM/l) levels were probably indicative of stress; glucose was the only carbohydrate present in appreciable amounts in the serum, although traces of glucuronic acid and rhamnose were found. Serum total cholesterol was 3.91 mM/l, organically bound phosphorus 1.99 mM/l and total proteins 2.84 g%. Three major protein fractions were evident from cellulose acetate electrophoresis and at least 11 peaks were demonstrable by acrylamide gel electrophoresis. Latimeria serum lacks a protein component with a mobility approaching that of human serum albumin. Serum osmolarity (932 mOsm/l) was somewhat lower than that of sea water collected at the site of capture of the specimen (1035 mOsm/l). Evolutionary implications of the similarity of Latimeria serum chemistry to that of other marine fishes are discussed.

A comparison was made of environmental salinities, ability to survive in fresh water and upper salinity tolerance for over 20 species of the teleost genus Fundulus. All species of the genus occur, at times, in fresh water and are able to survive in this medium in the laboratory. Species found in brackish environments have upper salinity tolerances ranging from 74-114%o, while most species characteristic of fresh waters are unable to survive in salinities above 29%o. Notable exceptions are F. zebrinus, an inland species commonly found in saline waters, F. diaphanus, a freshwater form which often enters dilute brackish estuaries and F. waccamensis, a Pleistocene lacustrine derivative of F. diaphanus. Since brackish-water species are tolerant of life in fresh water while the reverse is not the case, it is suggested that freshwater species of Fundulus were derived from fully euryhaline ancestors which gradually lost the ability to live in sea water during extended isolation from brackish or marine environments.