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The Nature of Living Things

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Bioinformatics

Part of the book series: Computational Biology ((COBO,volume 21))

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Abstract

This chapter attempts to cover all of biology above the molecular level. Particular attention is devoted to genes and genome, given their importance within bioinformatics. Hence, the mechanisms of DNA replication and the structure of chromosomes are covered in some detail. Gene expression (transcription and translation) is accorded similar attention. Ontogeny (development) includes coverage of epigenesis and r-and K-selection. Hence, intracellular molecular machinery, the cell cycle and higher-level processes such as evolution are all covered.

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Notes

  1. 1.

    Kempner and Miller (1968).

  2. 2.

    See Kellermayer et al. (1986).

  3. 3.

    Chan (2006) and Westermann (2010) are useful reviews.

  4. 4.

    According to Abbe’s law, the resolution \(\Delta x = \lambda / 2 (\mathrm{N.A.})\), where \(\lambda \) is the wavelength of the illuminating light and N.A. is the numerical aperture of the microscope condenser. This barrier has now been broken by some remarkable new techniques developed by S.W. Hell, notably stimulated emission depletion (STED) and ground state depletion (GSD) microscopies, based on reversible saturated optical fluorescence transitions (RESOLFT) between two states of a fluorescent marker, typically a dye introduced into the living cell. The resolution is approximately given by \(\Delta x_\mathrm{Abbe} / \sqrt{1 + I/I_\mathrm{sat}}\), where I is the actual illuminating irradiance and \(I_\mathrm{sat}\) is the irradiance needed to saturate the transition.

  5. 5.

    See Hillman (1991) for an extended discussion.

  6. 6.

    See Ellis (2001).

  7. 7.

    Solomon (1960).

  8. 8.

    See Kellenberger (1972) for a review.

  9. 9.

    Except near the end of the process, when \(\bar{a}\) and \(\bar{b}\) become very small.

  10. 10.

    E.g., Wakamoto et al. (2005).

  11. 11.

    See Lechler and Fuchs (2005).

  12. 12.

    The events of growth and division are not really akin to printing multiple copies of a book, or photocopying pages. It is not, strictly speaking, correct to call the process whereby adult organisms create new organisms—offspring—“reproduction”: Parents do not reproduce themselves when they make a baby; even when the baby is grown up, it might be quite different, in appearance and behaviour, from its progenitors. In a literary analogy, this kind of process is akin to writing a new book (a derivative work) by gathering material from primary sources, or previously existing secondary sources.

  13. 13.

    A good example of a protein subjected to degradation is cyclin, which has the regulatory function mentioned above and whose concentration rises and then falls during mitosis.

  14. 14.

    1. Phenotypical characters depend on genes. Each gene can vary, the ensemble of variants being known as alleles. In species reproducing sexually, each new individual receives one allele from the father and one from the mother. 2. When an individual reproduces, it transmits to each offspring the paternal allele with probability 1/2 and the maternal allele with probability 1/2. 3. The actual transmission events are independent for each independently conceived offspring.

  15. 15.

    This fact is used to “explain” social insect behaviour.

  16. 16.

    There are some exceptions; for example, Streptomyces coelicolor has a linear genome.

  17. 17.

    So called because their abnormal base composition, usually greatly enriched in C-G pairs (CpG), results in satellite bands appearing near the main DNA bands when DNA is separated on a CsCl density gradient.

  18. 18.

    Archaeal and bacterial genomes contain clustered regularly interspaced short palindromic repeats (CRISPR; see, e.g., Sander and Joung 2014). They have found technological application as a way of genome editing.

  19. 19.

    Most English dictionaries give only one meaning for exon, namely one of four officers acting as commanders of the Yeomen of the Guard of the Tower of London.

  20. 20.

    For a concrete example see Hittinger and Carroll (2007).

  21. 21.

    Shapiro (1992).

  22. 22.

    Regarding the remainder, about 5 % is considered to be conserved (by comparison with the mouse); 1.2 % is estimated to be used for coding proteins, and the remaining 3.8 % is referred to as “noncoding,” although conservation of sequence is taken to imply significant function (it seems very probable that this “noncoding” DNA is used to encode the small interfering RNA used to supplement protein-based transcription factors as regulatory elements). That still leaves the enigma of the remaining 40–50 % that is neither repetitive nor coding in any sense understood at present.

  23. 23.

    Taft et al. (1992). Note the connexion between alternative splicing and Tonegawa’s mechanism for generating B-cell lymphocyte (and hence antibody) diversity in the immune system (Sect. 10.5).

  24. 24.

    Some groups of genes, typically those related functionally (such as successive enzymes in a metabolic pathway), are organized into “operons” by a single promoter site and are therefore transcribed together (see also Chap. 16).

  25. 25.

    Kim et al. (2006).

  26. 26.

    E.g., Karlin and Brendel (1993).

  27. 27.

    Another curiosity is that certain DNA sequences display extraordinarily long-range (\(10^4\) base pairs or more) correlations (see, e.g., Voss 1992).

  28. 28.

    See, for example, Jenuwein and Allis (2001), and Richards and Elgin (2002).

  29. 29.

    Audit et al. (2002).

  30. 30.

    The MHC (major histocompatibility complex) is a system of proteins residing on the surface of a cell that complexes with certain oligopeptides derived from a sample of the internal proteins of the cell.

  31. 31.

    The antibody is a protein made up from several different polypeptide chains. Part of the molecule is the same for all antibodies and part is unique. Tonegawa (1983) demonstrated that the diversity of antibodies was due to somatic generation of genetic diversity among the genes coding for the variable (unique) part.

  32. 32.

    Percus et al. (1993).

  33. 33.

    A quasispecies may be defined as a cluster of genomes in sequence space, the diameter of the cluster being sufficiently small such that almost every sequence can “mate” with every other one and produce viable offspring. The sequence at the centre of the cluster is called the master sequence. If the error rate is above the threshold, in principle all possible sequences will be found. See also Sect. 10.9.2.

  34. 34.

    Kornyshev and Leikin (2001).

  35. 35.

    See Arber (1998).

  36. 36.

    Blake et al. (2003), Raser and O’Shea (2005).

  37. 37.

    The transformation is given by: \(\downarrow \begin{array}{c} \text {A G C T} \\ \text {U C G A} \end{array}\).

  38. 38.

    See Fernández (1989).

  39. 39.

    Suppression of transcription is not perfect. There appears to be a basal rate of transcription of some genes even in tissues in which they are not required. See Chelly et al. (1989) and Sarkar and Sommer (1989).

  40. 40.

    Whereas a single RNAp operates in prokaryotes, there are at least three distinct ones in eukaryotes, accompanied by a host of “general transcription factors,” which considerably increases the possible combinations of regulatory agents.

  41. 41.

    The conventional view is that mammalian methylation occurs exclusively, or at least predominantly, at CpG pairs, but see, e.g., Doerfler et al. (1990) and Guo et al. (2014).

  42. 42.

    Useful references for this section are Doerfler et al. (1990), Ramsahoye et al. (1665) and Bird (2002).

  43. 43.

    Voinnet (2001); Ding and Voinnet (2014).

  44. 44.

    See Table 3.1 for the nucleic acid to amino acid transformation.

  45. 45.

    This is a very basic notion that crops up throughout biology. At present, there is no satisfactory universal formulation, however, but many interesting models have been proposed and investigated, including those of Érdi and Barna (1984) for neurogenesis, and Luthi et al. (1998) for neurogenesis in Drosophila. All of these models reduce to the basic formulation for the regulator (Sect. 9.4), discussed by Ashby (1956).

  46. 46.

    Allometric relations are of the type \(y = bx^a\), where a and b are constants. \(a=1\) corresponds to isometry.

  47. 47.

    Luthi et al. (1998).

  48. 48.

    Goldberg et al. (2007).

  49. 49.

    See Gilbert (1991) for a critique and Buss and Blackstone (1991) for an experimental exploration.

  50. 50.

    It is fairly well known that both Darwin and Wallace contributed independently; perhaps less well known is that priority appears to belong to Patrick Matthew (1831).

  51. 51.

    See Kirchner (2002) regarding limits on the rate of the filling process.

  52. 52.

    See Stanley (1975) for a full discussion.

  53. 53.

    McAndrew (2002).

  54. 54.

    Marshall (2011).

  55. 55.

    The fitness of a phenotypic trait is defined as a quantity proportional to the average number of offspring produced by an individual with that trait, in an existing population. In the model, the fitness of a genotype \(\mathbf {s}\) is proportional to the average number of offspring of an individual possessing that genotype.

  56. 56.

    See Peliti (1996) for a comprehensive treatment.

  57. 57.

    Cf. Sect. 7.2; see Jongeling (1996) for a critique.

  58. 58.

    For example the takahe feeds almost exclusively on snow grass.

  59. 59.

    Newman (1996).

  60. 60.

    See also Sect.  9.7

  61. 61.

    See White (1994).

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    Jeremy Ramsden

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Ramsden, J. (2015). The Nature of Living Things. In: Bioinformatics. Computational Biology, vol 21. Springer, London. https://doi.org/10.1007/978-1-4471-6702-0_10

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