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Because genes could explain so much in the biomedical sciences, in the twentieth century it was tempting to assume they could explain everything. So, for many, the bioinformatic analysis of genomes came to mean the bioin formatic analysis of genes and their products. However, bioinformatics slowly became less gene-centered. Evolutionary bioinformatics – the `new bioinformatics΄ – views genomes as channels conveying multiple forms of information through the generations from the distant past to the present. [ABSTRACT FROM AUTHOR]

The formation of different languages and of distinct species, and the proofs that both have been developed through a gradual process, are curiously the same. … Languages, like organic beings, can be classed in groups under groups. … A language, like a species, when once extinct, never … reappears. The same language never has two birthplaces …. The survival or preservation of certain favoured words in the struggle for existence is natural selection. [ABSTRACT FROM AUTHOR]

Aristotle wrote that the form-giving essence, the eidos, ˵does not become part of the embryo, just as no part of the carpenter enters the wood he works…but the form is imparted by him to the material″ [2, 3]. A carpenter will often hold the information for imparting form to wood in his head. If he wishes to communicate this information to other carpenters separated from himself in time and space, he has to choose symbols and a code. The symbols, D, O, and W, if repeated and arranged in the sequence W, O, O, and D, would be meaningless unless the receiver knew the transmitting carpenter΄s code. [ABSTRACT FROM AUTHOR]

Information has many forms. If you turn down the corner of a page to remind you where you stopped reading, then you have left a message on the page (`bookmark΄). In future you `decode΄ (extract information from) the bookmark with the knowledge that it means ˵continue here.″ A future historian might be interested in where you paused in your reading. Going through the book, he/she would notice creases suggesting that a flap had been turned down. Making assumptions about the code you were using, a feasible map of the book could then be made with your pause sites. It might be discovered that you paused at particular sites – say at the ends of chapters. In this case pauses would be correlated with the distribution of the book΄s `primary information.΄ Or perhaps there was a random element to your pausing – perhaps when your partner wanted the light out. In this case pausing would be influenced by your pairing relationship. While humans not infrequently get in a flap about their pairing relationships, we shall see that flaps are useful metaphors when we observe DNA molecules in a flap about their pairing relationships. [ABSTRACT FROM AUTHOR]

The sequence of a single-stranded nucleic acid is referred to as its primary structure. When it forms a duplex by pairing with a complementary single strand it adopts a secondary structure. Chargaff΄s first parity rule (PR1) for duplex DNA was consistent with the Watson-Crick idea of a base in one strand of the duplex pairing with a complementary base in the other strand of the duplex. This interstrand base pairing stabilized the secondary structure (Fig. 2.1). By the same token, the existence of a parity rule for single strands (PR2) suggested intrastrand base pairing. At least by virtue of the composition of the stems in stem-loop secondary structures, there should be approximately equivalent quantities of the classical pairing bases. [ABSTRACT FROM AUTHOR]

A nucleic acid sequence has three fundamental characteristics – its length, its base composition, and its sequence. If you know the sequence then you can calculate length and base composition with great precision. However, before the emergence of sequencing technologies in the 1970s there were biochemical methods that could provide values for length and base composition, albeit less precisely. Furthermore, Chargaff and his colleagues developed a method for evaluating a particular sequence characteristic – base clustering – that could distinguish DNA samples on the basis of sequence differences. [ABSTRACT FROM AUTHOR]

Members of a biological species vary. We acknowledge as a ˵variation″ a character in an organism that is different from the character seen in most other members of its species. Hence the organism would be called a ˵variant.″ The difference may be in number, or in arrangement, or in an individual character itself. Long before the nature of mutation at the DNA level was understood, Bateson suggested that these distinctions were fundamental. [ABSTRACT FROM AUTHOR]

If it had inherited a mutated gene that impaired its ability to run, then, relative to its companions, a deer would be defective and so subject to selective devourment by predators. This is Tennyson΄s ˵Nature, red in tooth and claw,″ and Darwin΄s ˵natural selection.″. [ABSTRACT FROM AUTHOR]

The introduction of slightly new elements into a method already established varies it beneficially; the new is soon fused with the old, and the monotony ceases to be oppressive. But if the new be too foreign, we cannot fuse the old and the new – nature seeming to hate equally, too wide a deviation from ordinary practice, and none at all. This fact reappears in heredity as the beneficial effects of occasional crossing on the one hand, and on the other, in the generally observed sterility of hybrids. If heredity be an affair of memory, how can an embryo, say of a mule, be expected to build up a mule on the strength of but two mule memories? Hybridism causes a fault in the chain of memory, and it is to this cause that the usual sterility of hybrids must be referred. [ABSTRACT FROM AUTHOR]

Evolutionary selective pressures sometimes act to preserve nucleic acid features at the expense of encoded proteins. That this can occur in the case of nucleic acid secondary structure was noted in Chapter 5. That this might also apply to the species-dependent component of the base composition, (G+C)%, was shown by Sueoka in 1961 [2]. The amino acid composition of the proteins of bacteria is influenced, not only by the demands of the environment on the proteins, but also by the (G+C)% of the genome encoding those proteins. [ABSTRACT FROM AUTHOR]

Genetic information is `written΄ by a variation in sequence on the one hand, and the physical stability of the double-stranded structure is determined by the base composition on the other hand. … DNA is found to consist of a number of homostability regions which come from homogenous base sequences consisting of 500 base pairs or more. … Biologically, it is hard … to believe that such regional homostability originates in a fundamental characteristic of the genetic code itself. It is quite plausible … that the homostability region plays an important part somewhere in the biological process within which the DNA is closely related. If so, then the evolutionary selective force can be considered to have fixed such regions of DNA. From the size of the homostability region, recombination might be one possible process which is aided by it. In any case, the wobble bases [in codons] must give the necessary redundancy to make a homostability region without spoiling the biological meaning of the genetic code. [ABSTRACT FROM AUTHOR]

The tasks of evolutionary bioinformatics (EB) are to identify the forms of information that genomes convey and show how potential conflicts between different forms are reconciled. Apparent redundancies (e.g. diploidy; Chapter 2), and beliefs in the existence of `neutral΄ mutations (Chapter 7), and of `junk΄ DNA (see Chapter 15), tended to support the view that there is much vacant genome space. Hence there is `room for all΄ in the journey of the genes through the generations. Suggestions that there might be conflicts between different forms of information were not taken too seriously. However, when genomic information was thought of in the same way as the other forms of information with which we are familiar (Chapters 2-4), it became evident that apparent redundancies might actually play important roles – error – detection and correction, and much more. The possibility of conflict could no longer be evaded. The essential argument of this book is that many puzzling features of genomes can best be understood in such terms, as will be emphasized in this and subsequent chapters. [ABSTRACT FROM AUTHOR]

First a digression on nuclei. Organisms can be divided into those whose cells do not have a nucleus, the single celled ˵prokaryotes″ (Greek: pro = before; karyon = nucleus), and those whose cells have a nucleus, the single- or multicelled ˵eukaryotes″ (Greek: eu = good or normal; karyon = nucleus). Prokaryotes include species of bacteria (eubacteria) and archaea (archaebacteria) – a bacteria–like group sometimes found in extreme environments (e.g. hot springs). Eukaryotes (eukarya) include all species of animals and plants, both single–celled (protozoa, protophyta) and multi–celled (metazoa, metaphyta) – that you and me!. [ABSTRACT FROM AUTHOR]

Some things are more complex than others. We feel intuitively that highly complex things are associated with more information than less complex things. But this will not suffice for Homo bioinformaticus. Information and complexity must be measured. When this is done, amazing ˵principles of order″ emerge from large amounts of seemingly disparate data. [ABSTRACT FROM AUTHOR]

Given the ˵struggle for existence″ an organism might hope to outshine its competitors by virtue of the excellence of its positive characters (e.g. greater speed, longer neck). But an organism that could also (i) identify, defend against, and attack its foes, and (ii) identify and support its friends, would seem to have an even greater advantage. To identify is to allow discrimination – friend or foe? – the former classification being non–dangerous (potentially unharmful), the latter classification being dangerous (potentially harmful). For this, friend and foe must have distinguishable characters and the organism must both detect these characters, and know which characters are likely to associate with non-danger (friend) and which characters are likely to associate with danger (foe). After this discrimination, there must then be a response (either non–alarm, or alarm) that, in turn, would lead to a variety of other responses of an adaptive nature (e.g. escape from, or destroy, the foe). [ABSTRACT FROM AUTHOR]

While, given the expansion of the world population, it cannot be guaranteed that it will always be so, currently one accepts as a temporary discomfort short periods of crowding, as in a crowded elevator or subway train. However, if, like most intracellular macromolecules, one were both blind and deaf, the need to communicate by touch might make crowding an option of choice. It seems likely that the first cells to evolve soon discovered the advantage of intracellular crowding, which persists to this day [2]. Indeed, the physiological environment of enzymes is very different from the environment we can normally create in the test-tube [ABSTRACT FROM AUTHOR]

With the notable exceptions of Butler and Miescher, in the nineteenth century the information concept as applied to biological molecules did not extend to information error and the need for its detection and correction (Chapter 2). Miescher in 1892 thought that: ˵Sexuality is an arrangement for the correction of these unavoidable stereometric architectural defects in the structure of organized substances″ (Chapter 3). While referring to ˵left handed coils″ being ˵corrected by right-handed coils,″ at that time he was unable to relate this to ˵nuclein,″ a new substance he had discovered, later known as DNA. However, he appreciated that correction would require some sort of yardstick (i.e. ˵right hand coils″) to permit the fact of error in a molecule (i.e. ˵left hand coils″) to be detected, and then appropriately corrected. [ABSTRACT FROM AUTHOR]

In the biological sciences few generalizations are absolute and we have already noted strange bases in RNA in addition to the usual - A, C, G and U (Fig. 5.1). For many purposes DNA can be considered solely in terms of its four major bases -A, C, G and T. However, in written languages single letters are sometimes qualified with accents. The words gène and gêne have very different meanings in French. We should not be surprised to find that there are similar qualifications in the DNA language. The most evident of these is methylcytosine, where the base C acquires a chemical grouping (methyl) [2]. Thus, in many organisms DNA has five letters - A, C, Me-C, G and T. Apart from the four regular bases, there is a pattern of methylation at intervals along a DNA sequence. [ABSTRACT FROM AUTHOR]

How we ourselves acquire, store and transmit mental information – how our minds process (input, manipulate and output) information – would seem to be ultimate questions in bioinformatics. Having `solved΄ the corresponding questions on genetic information in the 50s and 60s, Crick moved to brain research in 1976. One would have thought the two rules for his success in genetics would still apply: seek the simplest experimental system; find the store first and then work out how it fills and empties. For his experiments Crick had chosen the smallest known biological forms – the viruses that infect bacteria. And he went directly to the genetic store – DNA. When its structure was known, solutions to the acquisition problem (replication and mutation) and the transmission problem (transcription and translation) fell neatly into place. But neither rule was to be followed in his brain research. [ABSTRACT FROM AUTHOR]

Information has many forms. If you turn down the corner of a page to remind you where you stopped reading, then you have left a message on the page (˵bookmark″). In future you ˵decode″ (extract information from) the bookmark with the knowledge that it means, ˵continue here.″ A future historian might be interested in where you paused in your reading. Going through the book, he/she would notice creases suggesting that a flap had been turned down. Making assumptions about the code you were using, a feasible map of the book could then be made with your pause sites. It might be discovered that you paused at particular sites, say at the ends of chapters. In this case pauses would be correlated with the distribution of the book΄s ˵primary information.″ Or perhaps there was a random element to your pausing – perhaps when your partner wanted the light out. In this case pausing would be influenced by your pairing relationship. While humans not infrequently get in a flap about their pairing relationships, we shall sec that flaps are useful metaphors when we observe DNA molecules in a flap about their pairing relationships. [ABSTRACT FROM AUTHOR]