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Biomedical subjects

T Cavalier-Smith

Publications and source records attributed to T Cavalier-Smith.

At least 55 records · Page 3Linked to original sources

Bacterial DNA segregation: its motors and positional control.

A model for DNA segregation in bacteria is proposed which involves not merely growth of the cell membrane and wall, as previously assumed, but also the active movement of one of the two chromosome sister origins by a DNA helicase enzyme and of the chromosome termini and the bulk of the chromosomes by supercoiling tension exerted by DNA gyrase. This provides a unified mechanism for DNA chromosome movement in prosthecate budding bacteria as well as for bacteria that undergo binary fission. The positional control of DNA segregation and the plane of cell division depend, I suggest, on four things: (1) the attachment of the daughter chromosome termini to the cell wall in a position adjacent to the new cell poles at about the time of septation, (2) the displacement of the parental chromosome terminus from this attachment site by the mobile origin, which attaches itself instead to the wall at that point, (3) the movement of the chromosome terminus to a new location in between the daughter origins by the tension of supercoiling, and (4) the determination of the location of the future septum at the position occupied by the chromosome terminus at the time of septal initiation; septum-initiation proteins are postulated to achieve this by binding directly or indirectly to the chromosome terminus. This mechanism automatically ensures ordered DNA segregation in rapidly growing bacteria with more than two sister origins of replication.

Cell Division↗

The origin of cells: a symbiosis between genes, catalysts, and membranes.

The gap between early molecular evolution and the origin of the first cell may have been bridged by a photoheterotrophic obcell, consisting of genes and ribosomes attached to the outer surface of a phospholipid vesicle containing a light-driven proton pump and a proton-driven pyrophosphate synthase. I argue that the obcell was the substratum for the origin of DNA replication; DNA segregation by the growth and division of the peptidoglycan murein; periplasmic solute-binding proteins; bioenergetics, including the F0F1 proton-driven ATP synthase; active transport of calcium; and facilitated diffusion of nutrients across membranes, and that it played the major role in the replacement of ribozymes by protein catalysts. Curved growth of the peptidoglycan and a mutation causing septum formation produced the first true cell. Evolution of porins, sodium extrusion and potassium import, conversion of the facilitated diffusion proteins to active pumps, and the evolution of intermediary metabolism, carbon and nitrogen fixation, and of substrate level phosphorylation, completed the origin of the first negibacterial eubacterium, from which all other cells evolved, and from which they have inherited most of their major catalytic properties--with the notable exceptions of reverse transcriptase, RNA splicing, and methanogenesis, all of which I believe evolved very much later.

Animals↗

Chromatin from the unicellular red alga Porphyridium has a nucleosome structure.

We have isolated a crude nuclear preparation from the unicellular red alga Porphyridium aerugineum and investigated the structure of Porphyridium chromatin. Electrophoresis of deproteinized DNA fragments produced by micrococcal nuclease digestion of Porphyridium nuclei gives a typical ladder pattern, indicative of a repeating structure. The DNA repeat-length, calculated from plots of multimer length against multimer number, varies somewhat between different digestions, ranging from 160 to 180 base-pairs (average 173). We interpret this as evidence of heterogeneity in repeat-length; the calculated repeat-length depends on the extent of digestion because chromatin sub-populations with longer repeat-lengths are on average digested earlier. Polyacrylamide/sodium dodecyl sulphate gel electrophoresis of basic proteins purified from Porphyridium nuclear preparations gives a pattern characteristic of core histones. Although our interpretation is complicated by some degradation, the result strongly suggests that Porphyridium chromatin contains each of the four core histones and that they are similar to those of higher eukaryotes. This, together with the micrococcal nuclease digestion results, demonstrates that Porphyridium chromatin is not fundamentally different from that of higher eukaryotes.

Base Composition↗

Eukaryote kingdoms: seven or nine?

The primary taxa of eukaryote classification should be monophyletic and based on fundamental cell structure rather than nutritional adaptive zones. The classical two kingdom classification into "plants" and "animals" and the newer four kingdom classifications into "protis", "fungi" "animals" and "plants" are therefore both unsatisfactory. Eukaryotes can be classified into nine kingdoms each defined in terms of a unique constellation of cell structures. Five kingdoms have plate-like mitochondrial cristae: (1) Eufungi (the non-ciliated fungi, which unlike the other eight kingdoms have unstacked Golgi cisternae), (2) Ciliofungi (the posteriorly ciliated fungi), (3) Animalia (Animals, sponges, mesozoa, and choanociliates; phagotrophs with basically posterior ciliation), (4) Biliphyta (Non-phagotrophic, phycobilisome-containing, algae; i.e. theGlaucophyceae and Rhodophyceae), (5) Viridiplantae (Non-phagotrophic green plants, with starch-containing plastids). Kingdom (6), the Euglenozoa, has disc-shaped cristae and an intraciliary dense rod and may be phagotrophic and/or phototrophic with plastids with three-membraned envelopes. Kingdom (7), the cryptophyta, has flattened tubular cristae, tubular mastigonemes on both cilia,m and starch in thecompartment between the plastid endoplasmic reticulum and the plastid envelope; their plastids, if present, have phycobilins inside the paired thylakoids and chlorophyll c2. Kingdom (8), the Chromophyta, has tubular cristae, together with tubular mastigonemes on one anterior cilum and/or a plastid endoplasmic reticulum and chlorophyll c1 + c2. Members of the ninth kingdom, the Protozoa, are mainly phagotrophic, and have tubular or vesicular cristae (or lack mitochondria altogether), and lack tubular mastigonemes on their (primitively anterior) cilia; plastids if present have three-envelop membranes, chlorophyll c2, and no internal starch, and a plastid endoplasmic reticulum is absent. Kingdoms 4-9 are primitively anteriorly biciliate. Detailed definitions of the new kingdoms and lists of the phyla comprising them are given. Advantages of the new system and its main phylogenetic implications are discussed. A simpler system of five kingdoms suitable for very elementary teaching is possible by grouping the photosynthetic and fungal kindoms in pairs. Various compromises are possible between the nine and five kingdoms systems; it is suggested that the best one for general scientific use is a system of seven kingdoms in which the Eufungi and Ciliofungi become subkingdoms of the Kingdom Fungi, and the Cryptophyta andChromophyta subkingdoms of th Kingdom Chromista; the Fungi, Viridiplantae, Biliphyta, and Chromista can be subject to the Botanical Code of Nomenclature, while the Zoological Code can govern the Kingdoms Animalia, Protozoa and Euglenozoa...

Animals↗

r- and K-tactics in the evolution of protist developmental systems: cell and genome size, phenotype diversifying selection, and cell cycle patterns.

I outline the significance for protist evolution of the r-, K-selection spectrum,, and of my earlier theory that the most fundamental way organisms adapt to this spectrum is by evolutionary variations in their cell volumes, cell growth rates and genome sizes. Then I introduce the concept of phenotype diversifying selection; this refers to those selective forces which favour an increase in the number of phenotypes produced during a single life cycle by an organism's genotype and epigenetic system. These ideas are then used to discuss the evolution of protist development, with special reference to modifications of the cell cycle whose evolutionary causes and consequences can be related to K-selection for large size and r-selection for rapid reproduction. The significance of multiple fission, syncytia, multicellularity, nuclear dimorphism plus polyploidy, and reversible polyploidy, is treated in detail. Predictions are made of the effects of these different developmental patterns on genome size and the distribution and amounts of nucleoskeletal RNA and heterochromatin. I suggest that heterochromatin exists primarily because of phenotype diversifying selection for differing nuclear volumes. The possibility of applying these ideas to other cell properties like mitotic or cytokinetic mechanisms is also briefly discussed.

Animals↗

Nuclear volume control by nucleoskeletal DNA, selection for cell volume and cell growth rate, and the solution of the DNA C-value paradox.

The 40,000-fold variation in eukaryote haploid DNA content is unrelated to organismic complexity or to the numbers of protein-coding genes. In eukaryote microorganisms, as well as in animals and plants, DNA content is strongly correlated with cell volume and nuclear volume, and with cell cycle length and minimum generation time. These correlations are simply explained by postulating that DNA has 2 major functions unrelated to its protein-coding capacity: (1) the control of cell volume by the number of replicon origins, and (2) the determination of nuclear volume by the overall bulk of the DNA: cell growth rates are determined by the cell volume and by the area of the nuclear envelope available for nucleocytoplasmic transport of RNA, which in turn depends on the nuclear volume and therefore on the DNA content. During evolution nuclear volume, and therefore DNA content, has to be adjusted to the cell volume to allow reasonable growth rates. The great diversity of cell volumes and growth rates, and therefore of DNA contents, among eukaryotes results from a varying balance in different species between r-selection, which favours small cells and rapid growth rates and therefore low DNA C-values, and K-selection which favours large cells and slow growth rates and therefore high DNA C-values. In multicellular organisms cell size needs to vary in different tissues: size differences between somatic cells result from polyteny, endopolyploidy, or the synthesis of nucleoskeletal RNA. Conflict between the need for large ova and small somatic cells explains why lampbrush chromosomes, nurse cells, chromatin diminution and chromosome elimination evolved. Similar evolutionary considerations clarify the nature of polygenes, the significance of the distribution of haploidy, diploidy and dikaryosis in life cycles and of double fertilization in angiosperms, and of heteroploidy despite DNA constancy in cultured cells, and other puzzles in eukaryote chromosome biology. Eukaryote DNA can be divided into genic DNA (G-DNA), which codes for proteins (or serves as recognition sites for proteins involved in transcription, replication and recombination), and nucleoskeletal DNA (S-DNA) which exists only because of its nucleoskeletal role in determining the nuclear volume (which it shares with G-DNA, and performs not only directly, but also indirectly by coding for nucleoskeletal RNA). Mechanistic and evolutionary implications of this are discussed.

Animals↗

Mitosis and microtuble assembly.

Microtubules reconstituted in vitro are identical in helical structure with tubules making up the mitotic spindle and both are formed by a helical condensation-polymerization mechanism. The protomer of microtubules is a heterodimer (alphabeta), of mol.wt. 110000 and sedimentation coefficient, SO25,w, 6S. This dimer has one binding site for colchicine or podophyllotoxin, two sites for Vinca alkaloids, two sites for guanine nucleotides and Ca2+-binding sites. There is also a beta-chain phosphoserine. Modulation of these properties is discussed as a possible way of regulating the competence of tubulin to polymerize. Reconstituted microtubules depolymerize to a mixture of 30-36S oligomeric tubulin and 6S dimer molecules. The 30-36S tubulin appears as a ring or disc when made visible in the electron microscope by negative staining. Three pathways of microtubule assembly have been proposed involving this ring as an intermediate: (1) the uncoiling of these rings into protofilaments; (2) the stacking of rings into macrotubules; (3) the rings as a scaffold for the assembly of a short segment of microtubule helix. Finally, the regulation of mitosis is discussed in terms of recent studies of tubulin and its polymerization, and studies in vitro and in vivo of the process of mitotic-spindle formation and disassembly.

Alkaloids↗