An Interpretive Review of the Origin of Life Research

Life appears to be a natural property of matter, but the problem of its origin only arose after early scientists refuted continuous spontaneous generation. There is no chance of life arising ‘all at once’, we need the standard scientific incremental explanation with large numbers of small steps, an approach used in both physical and evolutionary sciences. The necessity for considering both theoretical and experimental approaches is emphasized. After describing basic principles that are available (including the Darwin-Eigen cycle), the search for origins is considered under four main themes. These are the RNA-world hypothesis; potential intermediates between an RNA-world and a modern world via the evolution of protein synthesis and then of DNA; possible alternatives to an RNA-world; and finally the earliest stages from the simple prebiotic systems to RNA. The triplicase/proto-ribosome theory for the origin of the ribosome is discussed where triples of nucleotides are added to a replicating RNA, with the origin of a triplet code well-before protein synthesis begins. The length of the code is suggested to arise from the early development of a ratchet mechanism that overcomes the problem of continued processivity of an RNA-based RNA-polymerase. It is probable that there were precursor stages to RNA with simpler sugars, or just two nucleotides, but we do not yet know of any better alternatives to RNA that were likely to arise naturally. For prebiotic stages (before RNA) a flow-reactor model is suggested to solve metabolism, energy gradients, and compartmentation simultaneously – thus the intense interest in some form of flow reactor. If an autocatalytic cycle could arise in such a system we would be major steps ahead. The most likely physical conditions for the origin of life require further clarification and it is still unclear whether the origin of life is more of an entropy (information) problem (and therefore high temperatures would be detrimental), rather than a kinetic problem (where high temperatures may be advantageous).     

Moving up the hierarchy: A hypothesis on the evolution of a genetic sex determination pathway

A hypothesis on the evolutionary origin of the genetic pathway of sex determination in the nematode Caenorhabditis elegans is presented here. It is suggested that the pathway arose in steps, driven by frequency-dependent selection for the minority sex at each step, and involving the sequential acquisition of dominant negative, neomorphic genetic switches, each one reversing the action of the previous one. A central implication is that the genetic pathway evolved in reverse order from the final step in the hierarchy up to the first. The possible applicability of the model to the other well-characterized sex determination pathway, that of Drosophila melanogaster, and to sex determination in mammals, is discussed, along with some potential implications for pathway evolution in general. Finally, the specific molecular and population genetic questions that the model raises are described and some tests are proposed.     

Structure and Synthesis of Dopastin,an Inhibitor of Dopamine β-Hydroxylase

Dopastin, an inhibitor of dopamine β-hydroxylase of microbial origin, was shown to be N-[2(S)-nitrosohydroxylamino-3-methylbutyl] crotonamide based on chemical, spectroscopic and synthetic studies. The total synthesis of dopastin was completed in 8 steps starting from l-valinol. N-Nitrosohydroxylamino function was introduced through an oxaziran with retention of the absolute configuration in the final product. Thus, the 2S-configuration of dopastin was proved by the total synthesis. Racemic dopastin was also synthesized from isobutyraldehyde in 7 steps.     

Phylogenetic aspects of Cetacean origins: A morphological perspective

The evolutionary steps leading up to the origin of cetaceans involved pervasive changes in the masticatory apparatus, the ear, and limb morphology. These changes bear heavily on the phylogenetic relationships of Cetacea, and are investigated here on the basis of two of its earliest members:Pakicetus andAmbulocetus. A phylogenetic analysis of cetaceans, five groups of mesonychians, and five other groups of ungulates indicates thatPakicetus is the sister group to all other cetaceans, and that Cete (mesonychians and Cetacea) is a monophyletic group.     

Origin of the Eocene planktonic foraminifer Hantkenina by gradual evolution

Hantkenina is a distinctive planktonic foraminiferal genus characterized by the presence of tubulospines (robust hollow projections) on each adult chamber, from Middle and Upper Eocene marine sediments worldwide. Here we illustrate its evolutionary origin using c. 150 specimens from 30 stratigraphic intervals in two sediment cores from Tanzania. The specimens, which span an estimated time interval of 300 ka, show four intermediate steps in the evolution of the tubulospines that amount to a complete intergradation from Clavigerinella caucasica, which does not possess them, to Hantkenina mexicana, which does. Stable isotope analyses indicate that the transitional forms evolved in a deep planktonic habitat not occupied at that time by other species of planktonic foraminifera. We discuss the morphogenetic constraints involved in the evolutionary transition and propose an ecological/adaptive model for the selective pressures that resulted in the evolution of tubulospines. We compare our record with similar, recently described assemblages from Austria and Italy, and we update the biostratigraphy and systematic taxonomy of the key morphospecies involved in the transition.     

Contribution of processing events to the molecular heterogeneity of four banding types of phaseolin,the major storage protein of Phaseolus vulgaris L.

Summary The origin of the molecular heterogeneity of phaseolin was investigated by studying, both in vivo and in vitro, the synthesis and processing of four different banding types of phaseolin in five cultivars of Phaseolus vulgaris L. The results demonstrate: I) Newly-synthesized (unprocessed) phaseolin in all cultivars is composed of three major components. These differ between cultivars, both in charge and Mr. II) The processing of these precursors is highly conserved and consists of the co-translational cleavage of a signal peptide, two glycosylation steps in the endoplasmic reticulum and a further modification inside the protein bodies to give the mature form. III) Some of the molecular heterogeneity of each phaseolin banding type is due to a different extent of glycosylation of its polypeptide components.     

Drosophila sex combs as a model of evolutionary innovations

The diversity of animal and plant forms is shaped by nested evolutionary innovations. Understanding the genetic and molecular changes responsible for these innovations is therefore one of the key goals of evolutionary biology. From the genetic point of view, the origin of novel traits implies the origin of new regulatory pathways to control their development. To understand how these new pathways are assembled in the course of evolution, we need model systems that combine relatively recent innovations with a powerful set of genetic and molecular tools. One such model is provided by the Drosophila sex comb—a male‐specific morphological structure that evolved in a relatively small lineage related to the model species D. melanogaster. Our extensive knowledge of sex comb development in D. melanogaster provides the basis for investigating the genetic changes responsible for sex comb origin and diversification. At the same time, sex combs can change on microevolutionary timescales and differ spectacularly among closely related species, providing opportunities for direct genetic analysis and for integrating developmental and population‐genetic approaches. Sex comb evolution is associated with the origin of novel interactions between Hox and sex determination genes. Activity of the sex determination pathway was brought under the control of the Hox code to become segment‐specific, while Hox gene expression became sexually dimorphic. At the same time, both Hox and sex determination genes were integrated into the intrasegmental spatial patterning network, and acquired new joint downstream targets. Phylogenetic analysis shows that similar sex comb morphologies evolved independently in different lineages. Convergent evolution at the phenotypic level reflects convergent changes in the expression of Hox and sex determination genes, involving both independent gains and losses of regulatory interactions. However, the downstream cell‐differentiation programs have diverged between species, and in some lineages, similar adult morphologies are produced by different morphogenetic mechanisms. These features make the sex comb an excellent model for examining not only the genetic changes responsible for its evolution, but also the cellular processes that translate DNA sequence changes into morphological diversity. The origin and diversification of sex combs provides insights into the roles of modularity, cooption, and regulatory changes in evolutionary innovations, and can serve as a model for understanding the origin of the more drastic novelties that define higher order taxa.     

Comparative Study of Bacillus thuringiensis Cry1Aa and Cry1Ac δ-Endotoxin Activation, Inactivation and In Situ Histopathological Effect in Ephestia kuehniella (Lepidoptera: Pyralidae)

A comparative study of different steps in the mode of action of the individual Bacillus thuringiensis kurstaki BNS3 Cry1Aa and Cry1Ac δ-endotoxins on E. kuehniella larvae was performed in order to investigate the origin of the difference in the response of this larvae to each of the latter. Proteolytic activation was shown to be one of the main steps impaired in E. kuehniella tolerance to Cry1Aa. The absence of two proteinase activities as well as an altered activity level observed in the case of Cry1Aa would be the consequence of proteinase-mediated tolerance of E. kuehniella to this toxin. In situ binding and histopathological effect analyses allowed concluding that the binding of the toxin to BBMV receptors is the key step in E. kuehniella tolerance to Cry1Aa toxin. The latter was slightly bound to apical membranes of epithelial cells that remained intact, whereas Cry1Ac was tightly bound to completely damaged cells basal membranes.     

Phylogenetic status of brown trout Salmo trutta populations in five rivers from the southern Caspian Sea and two inland lake basins,Iran: a morphogenetic approach

Interrelationships, origin and phylogenetic affinities of brown trout Salmo trutta populations from the southern Caspian Sea basin, Orumieh and Namak Lake basins in Iran were analysed from complete mtDNA control region sequences, 12 microsatellite loci and morphological characters. Among 129 specimens from six populations, seven haplotypes were observed. Based on mtDNA haplotype data, the Orumieh and southern Caspian populations did not differ significantly, but the Namak basin–Karaj population presented a unique haplotype closely related to the haplotypes of the other populations (0·1% Kimura two‐parameter, K2P divergence). All Iranian haplotypes clustered as a distinct group within the Danube phylogenetic grouping, with an average K2P distance of 0·41% relative to other Danubian haplotypes. The Karaj haplotype in the Namak basin was related to a haplotype (Da26) formerly identified in the Tigris basin in Turkey, to a Salmo trutta oxianus haplotype from the Aral Sea basin, and to haplotype Da1a with two mutational steps, as well as to other Iranian haplotypes with one to two mutational steps, which may indicate a centre of origin in the Caspian basin. In contrast to results of the mtDNA analysis, more pronounced differentiation was observed among the populations studied in the morphological and microsatellite DNA data, except for the two populations from the Orumieh basin, which were similar, possibly due to anthropogenic causes.     

Role ofLLD, a new locus for leaflet/pinna morphogenesis inPisum sativum

Properties of a mutant at theLLD (LEAF-LET DEVELOPMENT) locus in peaPisum sativum L. are reported in this paper. Plants homozygous for the Mendelian recessive mutationlld bear leaves in which a few to many leaflets are incompletely developed. Opposite pinnae of rachis nodes often formed fused incompletely developed leaflets. Thelld mutation was observed to abort pinna development at almost all morphogenetic stages. Thelld mutation demonstrated high penetrance and low expressivity. The phenotypes oflld plants intl, tac, tl tac, tl af andtl af tac backgrounds suggested that LLD function is involved in the separation of lateral adjacent blastozones differentiated on primary, secondary and tertiary rachides and lamina development in leaflets. The aborted development of tendrils and leaflets inlld mutants was related to deficiency in vascular tissue growth. The morphological and anatomical features of the leaflets formed on atl lld double mutant permitted a model of basipetal leaflet development. The key steps of leaflet morphogenesis include origin of the lamina by splitting of a radially symmetrical growing pinna having abaxial outer surface, opposite to the vascular cylinder, through an invaginational groove, differentiation of adaxial surface along the outer boundary of split tissue in the groove and expansion of the lamina ridges so formed into lamina spans.     

Worldwide pattern of multilocus structure in barley determined by discrete log-linear multivariate analyses

Summary Data from the electrophoretic assay for seven enzyme loci of 1,032 accessions of cultivated barley, Hordeum vulgare L., from the USDA world barley collection were analyzed for multilocus structure using discrete log-linear multivariate techniques. Three major steps were involved in the analysis: (i) identification and elimination of terms that have inconsequential effects in multilocus association; (ii) construction of a log-linear model that best describes the complete multilocus structure of the genetic system; and (iii) evaluation of each of the association terms included in the model. The results of analyses of two subsets of loci show that the multilocus genetic system of cultivated barley, including loci located on different chromosomes, is organized into hierarchically structured complexes of loci. Multilocus structure differs in various geographical regions of the world. The structure of barleys from Southwest Asia, the putative center of origin for cultivated barley, is intermediate for both subsets of loci. Differences increased progressively across the Eurasian-African landmasses in each direction with increasing distance from Southwest Asia, with the consequence that the barleys from West Europe, East Asia, and Ethiopia are maximally different from those of Southwest Asia and Middle South Asia.     

Helix bending as a factor in protein/DNA recognition

Normal vectors perpendicular to individual base pairs are a powerful tool for studying the bending behavior of B-DNA, both in the form of normal vector plots and in matrices that list angles between vectors for all possible base pair combinations. A new analysis program, FREEHELIX, has been written for this purpose, and applied to 86 examples of sequence-specific protein/DNA complexes whose coordinates are on deposit in the Nucleic Acid Data Base. Bends in this sample of 86 structures almost invariably follow from roll angles between adjacent base pairs; tilt makes no net contribution. Roll in a direction compressing the broad major groove is much more common than that which compresses the minor groove. Three distinct types of B-DNA bending are observed, each with a different molecular origin: (1) Localized kinking is produced by large roll at single steps or at two steps separated by one turn of helix. (2) Smooth, planar curvature is produced by positive and negative roll angles spaced a half-turn apart, with random side-to-side zigzag roll at intermediate points, rather than a tilt contribution that might have been expected theoretically. (3) Three-dimensional writhe results from significant roll angles at a continuous series of steps. Writhe need not change the overall direction of helix axis, if it is continued indefinitely or for an integral number of helical turns. A-DNA itself can be formally considered as possessing uniform, continuous writhe that yields no net helix bending. Smooth curvature is the most intricate deformation of the three, and is least common. Writhe is the simplest deformation and is most common; indeed, a low level of continuous writhe is the normal condition of an otherwise unbent B-DNA helix of general sequence. With one exception, every example of major kinking in this sample of 86 structures involves a pyrimidine–purine step: C–A/T–G, T–A, or C–G. Purine–purine steps, especially A–A, show the least tendency toward roll deformations. © 1998 John Wiley & Sons, Inc. Biopoly 44: 361–403, 1997     

Embryonic asymmetry: The left side gets all the best genes

The origin of left–right developmental asymmetry is a continuing puzzle, but some recent results provide new insights into the steps leading to organ asymmetry – implicating the homeobox protein Pitz-2 in one key step – and others support a model of symmetry-breaking that involves the chirality of microtubules.     

Amoeboid movement as a correlated walk

Summary The movement of slime-mold amoebae under isotropic conditions in two dimensions is represented as a Correlated Walk with straight steps of variable length. The steps are correlated via the angle turned through from step to step. The hypotheses and predictions of the model compare favourably with experimental data for Dictyostelium discoideum amoebae.This work was supported in part by an M. R. C. Grant # MA 5340.     

Genetics and modern human origins

The past decade has brought considerable debate on the subject of modern human origins. The nature of the transition from Homo erectus to archaic Homo sapiens to modern H. sapiens has been examined primarily in terms of the relative contribution of archaic populations to later moderns, both within and among geographic regions. The recent African origin model proposes that modern humans appeared first in Africa between 100,000 and 200,000 years ago, and then spread through the rest of the Old World, replacing preexisting populations.^1–6 This model has been referred to by a variety of names, including “replacement”, “Garden of Eden”, “Noah's Ark”, and “out of Africa”. The recent African origin model contrasts with the multiregional model, which proposes a species-wide transition to modern humans throughout the Old World during the past million years or more.^7–10 Indeed, some proponents of the multiregional model advocate placing Homo erectus and all subsequent species of Homo in the evolutionary species Homo sapiens.¹¹ This contrasts with the view that there were multiple hominid species during the Middle Pleistocene. The debate continues.^12,13 Although the multiregional model is often portrayed as proposing a simultaneous transition to anatomically modern humans in different geographic regions, it explicitly allows for varying degrees of continuity across time and space.¹⁰ This model, in the broad sense, does not rule out the possibility that modern human morphology appeared first in Africa and then spread through the rest of the Old World through gene flow. However, not all advocates of the multiregional model adhere to this specific subset of the general model.⁹ Comparison of the African and multiregional models is complicated by considering other, less extreme, hypotheses. Some versions of the recent African origin model imply a speciation event associated with the initial origin of modern humans. Another version, which suggests the possibility of some admixture between “moderns” leaving Africa and preexisting “archaics” elsewhere in the Old World,^14,15 is similar to some variants of the multiregional model, which also suggest that modern morphology appeared first in Africa, but involved admixture with other Old World populations.¹⁶ The major difference between these views appears to be the extent of admixture, although the exact level is never specified. A further complication is the possibility that multiple dispersals from Africa produced a more complicated pattern of worldwide variation.¹⁷     

On the theoretical and experimental modeling of initial stages of metabolism formation in prebiotic systems

A concept of the initial stages of chemical prebiotic evolution, which eliminates a number of difficulties in the problem of the origin of life and permits experimental verification, is proposed. According to this concept, a predecessor of living beings has to be sufficiently simple to allow its self-assembly during a geologically short time period. In addition, the predecessor has to possess autocatalytic properties, and an ability for further complication (evolution). A possible scenario of the initial steps of the origin of life in nature and inside an experimental facility is considered. In the scope of the scenario the model of a multivariant oligomeric autocatalyst coupled with phase-separated particles is described. Results of computational simulations of possible initial steps in chemical evolution are presented. The estimates obtained show that the emergence of autocatalytic oligomeric phase-separated systems is possible at reasonable values of kinetics parameters of involved chemical reactions in a small-scale flow reactor.     

Isolation and characterization of lambda b221poriCasnA, a plaque-forming specialized transducing phage carrying the origin of replication of the Escherichia coli chromosome

Summary A specialized transducing phage, b221poriCasnA has been isolated carrying oriC the origin of chromosomal replication of Escherichia coli. All phage genes required for lytic growth are retained, thus the phage is capable of lytic growth. The presence of the oriC locus confers upon infecting phage DNA the ability to replicate as a plasmid using only host DNA replication functions. The presence of both oriC and asnA markers has allowed the development of a plaque assay for origin function which can be used to identify mutants at these loci. Comparison of restriction endonuclease cleavage sites present on b221poriCasnA DNA to those on tis parent, b221 rex::Tn10 suggests the steps involved in the formation of the transducing phage.     

Nucleotide sequence of the region of the origin of replication of the broad host range plasmid RK2

Summary A DNA sequence cosisting of 617 base pairs (bp) from the region of the origin of replication of the broad-host range plasmid RK2 has been determined. Included within this sequence is a 393 bp HpaII restriction fragment that provides a functional origin or replication when other essential RK2 specified functions are provided in trans. Also contained in this sequence is a region, distinguished functionally from the replication origin, which is involved in the expression of inc ₂ incompatibility, i.e., the ability of derivatives of RK2 to eliminate a resident RK2 plasmid. The 617 bp sequence includes eight 17 base pair direct repeats with 5 located within the region required for a functional replication origin and 3 within the region involved in inc ₂ incompatibility. In addition, a 40 bp region rich in A-T followed by a 60 bp stretch having a high G+C content is present. Deletion evidence indicates that the A-T rich and possibly the G+C regions are required for a functional replication origin. Based on the evidence contained in this and the preceding paper (Thomas et al. 1980 b) a model will be presented for the involvement of these specific sequences in the initiation of RK2 DNA replication, plasmid maintenance and plasmid incompatibility.     

Proton translocation in cytochromec oxidase: Redox linkage through proximal ligand exchange on cytochromea 3

An analysis of resonance Raman scattering data from CO-bound cytochromec oxidase and from the photodissociated enzyme indicates that histidine may not be coordinated to the iron atom of cytochromea ₃ in the CO-bound form of the enzyme. Instead, the data suggest that either a water molecule or a different amino acid residue occupies the proximal ligand position. From these data, it is postulated that ligand exchange on cytochromea ₃ can occur under physiological conditions. Studies of mutant hemoglobins have demonstrated that tyrosinate binds preferentially to histidine in the ferric forms of the proteins. In cytochromec oxidase tyrosine residues are located near the histidine residues recently implicated in coordination to cytochromea ₃ (Shapleighet al., 1992; Hosleret al., this volume). Expanding on these concepts, we propose a model for proton translocation at the O₂-binding site based on proximal ligand exchange between tyrosine and histidine on cytochromea ₃. The pumping steps take place at the level of the peroxy intermediate and at the level of the ferryl intermediate in the catalytic cycle and are thereby consistent with the recent results of Wilkstrom (1989) who found that proton pumping occurs only at these two steps. It is shown that the model may be readily extended to account for the pumping of two protons at each of the steps.