B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 21
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To go from a circuit diagram to a prediction of the behavior of thesystem, we need detailed quantitative information, and to draw deductions fromthat information we need mathematics and computers.Such tools for quantitative reasoning are essential, but they are not all-powerful. You might think that, knowing how each protein influences each other protein, and how the expression of each gene is regulated by the products of others,we should soon be able to calculate how the cell as a whole will behave, just asan astronomer can calculate the orbits of the planets, or a chemical engineer cancalculate the flows through a chemical plant.
But any attempt to perform this featfor anything close to an entire living cell rapidly reveals the limits of our presentknowledge. The information we have, plentiful as it is, is full of gaps and uncertainties. Moreover, it is largely qualitative rather than quantitative. Most often, cellbiologists studying the cell’s control systems sum up their knowledge in simpleschematic diagrams—this book is full of them—rather than in numbers, graphs,and differential equations.To progress from qualitative descriptions and intuitive reasoning to quantitative descriptions and mathematical deduction is one of the biggest challenges forcontemporary cell biology. So far, the challenge has been met only for a few verysimple fragments of the machinery of living cells—subsystems involving a handful of different proteins, or two or three cross-regulatory genes, where theory andexperiment go closely hand in hand.
We discuss some of these examples later inthe book and devote the entire final section of Chapter 8 to the role of quantitationin cell biology.Knowledge and understanding bring the power to intervene—with humans,to avoid or prevent disease; with plants, to create better crops; with bacteria, toturn them to our own uses. All these biological enterprises are linked, because thegenetic information of all living organisms is written in the same language.
Thenew-found ability of molecular biologists to read and decipher this language hasalready begun to transform our relationship to the living world. The account ofcell biology in the subsequent chapters will, we hope, equip the reader to understand, and possibly to contribute to, the great scientific adventure of the twenty-first century.regulatoryDNAgenecodingregionmRNAtranscriptionregulatoryproteinFigure 1–47 A very simple regulatorycircuit—a single gene regulating itsown expression by the binding of itsproteinproductto its own regulatoryMBoC6m1.45/1.47DNA. Simple schematic diagrams suchas this are found throughout this book.They are often used to summarize whatwe know, but they leave many questionsunanswered. When the protein binds, doesit inhibit or stimulate transcription from thegene? How steeply does the transcriptionrate depend on the protein concentration?How long, on average, does a molecule ofthe protein remain bound to the DNA? Howlong does it take to make each moleculeof mRNA or protein, and how quickly doeseach type of molecule get degraded?As explained in Chapter 8, mathematicalmodeling shows that we need quantitativeanswers to all these and other questionsbefore we can predict the behavior ofeven this single-gene system.
For differentparameter values, the system may settleto a unique steady state; or it may behaveas a switch, capable of existing in one oranother of a set of alternative states; or itmay oscillate; or it may show large randomfluctuations.CHAPTER 1 END-OF-CHAPTER PROBLEMS39SummaryWHAT WE DON’T KNOWEukaryotic cells, by definition, keep their DNA in a separate membrane-enclosedcompartment, the nucleus.
They have, in addition, a cytoskeleton for support andmovement, elaborate intracellular compartments for digestion and secretion, thecapacity (in many species) to engulf other cells, and a metabolism that depends onthe oxidation of organic molecules by mitochondria. These properties suggest thateukaryotes may have originated as predators on other cells. Mitochondria—and,in plants, chloroplasts—contain their own genetic material, and they evidentlyevolved from bacteria that were taken up into the cytoplasm of ancient cells andsurvived as symbionts.Eukaryotic cells typically have 3–30 times as many genes as prokaryotes, andoften thousands of times more noncoding DNA.
The noncoding DNA allows forgreat complexity in the regulation of gene expression, as required for the construction of complex multicellular organisms. Many eukaryotes are, however, unicellular—among them the yeast Saccharomyces cerevisiae, which serves as a simplemodel organism for eukaryotic cell biology, revealing the molecular basis of manyfundamental processes that have been strikingly conserved during a billion years ofevolution. A small number of other organisms have also been chosen for intensivestudy: a worm, a fly, a fish, and the mouse serve as “model organisms” for multicellular animals; and a small milkweed serves as a model for plants.Powerful new technologies such as genome sequencing are producing strikingadvances in our knowledge of human beings, and they are helping to advance ourunderstanding of human health and disease.
But living systems are incredibly complex, and mammalian genomes contain multiple closely related homologs of mostgenes. This genetic redundancy has allowed diversification and specialization ofgenes for new purposes, but it also makes biological mechanisms harder to decipher. For this reason, simpler model organisms have played a key part in revealinguniversal genetic mechanisms of animal development, and research using thesesystems remains critical for driving scientific and medical advances.• What new approaches mightprovide a clearer view of the anaerobicarchaeon that is thought to haveformed the nucleus of the firsteukaryotic cell? How did its symbiosiswith an aerobic bacterium lead to themitochondrion? Somewhere on Earth,are there cells not yet identified thatcan fill in the details of how eukaryoticcells originated?• DNA sequencing has revealed a richand previously undiscovered worldof microbial cells, the vast majorityof which fail to grow in a laboratory.How might these cells be made moreaccessible for detailed study?• What new model cells or organismsshould be developed for scientists tostudy? Why might a concerted focuson these models speed progresstoward understanding a criticalaspect of cell function that is poorlyunderstood?• How did the first cell membranesarise?PROBLEMSWhich statements are true? Explain why or why not.1–2Horizontal gene transfer is more prevalent in single-celled organisms than in multicellular organisms.1–3Most of the DNA sequences in a bacterial genomecode for proteins, whereas most of the DNA sequences inthe human genome do not.Discuss the following problems.1–4Since it was deciphered four decades ago, somehave claimed that the genetic code must be a frozen accident, while others have argued that it was shaped by natural selection.
A striking feature of the genetic code is itsinherent resistance to the effects of mutation. For example,a change in the third position of a codon often specifies thesame amino acid or one with similar chemical properties.The natural code resists mutation more effectively (is lesssusceptible to error) than most other possible versions, asillustrated in Figure Q1–1.
Only one in a million computer-generated “random” codes is more error-resistant thanthe natural genetic code. Does the extraordinary mutationresistance of the genetic code argue in favor of its origin asa frozen accident or as a result of natural selection? Explainyour reasoning.number of codes (thousands)1–1Each member of the human hemoglobin genefamily, which consists of seven genes arranged in two clusters on different chromosomes, is an ortholog to all of theother members.201510naturalcode50051015susceptibility to mutation20Figure Q1–1 Susceptibility to mutation of the natural code shownrelative to that of millions of computer-generated alternative geneticcodes (Problem 1–4).
Susceptibility measures the average change inamino acid properties caused by random mutations in a genetic code.A small value indicates that mutations tend to cause minor changes.(Data courtesy of Steve Freeland.)Q1.140Chapter 1: Cells and Genomes1–5You have begun to characterize a sample obtainedfrom the depths of the oceans on Europa, one of Jupiter’s moons. Much to your surprise, the sample containsa life-form that grows well in a rich broth.
Your preliminary analysis shows that it is cellular and contains DNA,RNA, and protein. When you show your results to a colleague, she suggests that your sample was contaminatedwith an organism from Earth. What approaches mightyou try to distinguish between contamination and anovel cellular life-form based on DNA, RNA, and protein?1–6It is not so difficult to imagine what it means to feedon the organic molecules that living things produce. Thatis, after all, what we do. But what does it mean to “feed” onsunlight, as phototrophs do? Or, even stranger, to “feed” onrocks, as lithotrophs do? Where is the “food,” for example,in the mixture of chemicals (H2S, H2, CO, Mn+, Fe2+, Ni2+,CH4, and NH4+) that spews from a hydrothermal vent?1–7How many possible different trees (branching patterns) can in theory be drawn to display the evolution ofbacteria, archaea, and eukaryotes, assuming that they allarose from a common ancestor?1–8The genes for ribosomal RNA are highly conserved(relatively few sequence changes) in all organisms onEarth; thus, they have evolved very slowly over time.
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