* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Diversity in biological molecules
Survey
Document related concepts
History of molecular evolution wikipedia , lookup
Western blot wikipedia , lookup
Protein moonlighting wikipedia , lookup
Community fingerprinting wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Ancestral sequence reconstruction wikipedia , lookup
Expanded genetic code wikipedia , lookup
Protein adsorption wikipedia , lookup
Intrinsically disordered proteins wikipedia , lookup
List of types of proteins wikipedia , lookup
Genetic code wikipedia , lookup
Protein structure prediction wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Molecular ecology wikipedia , lookup
Transcript
Biodiversity Diversity in biological molecules H. John Newbury ABSTRACT One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of key molecules do not survive long term. However, it has also become apparent that there are different selective pressures on different parts of proteins so that some regions of a particular enzyme are highly conserved across different species while others are more variable. Using publicly available software along with collated amino acid sequence data, one can ‘line up’ particular enzyme sequences (such as trypsin) and discover that the highly conserved regions are those that contain amino acids located at the active site. Furthermore, different software can be used to exploit the variable regions of amino acid sequence to reconstruct the evolutionary pathway (phylogeny) of the species used. If, on the other hand, one examines biological molecules that act in processes less directly critical for survival, one finds tremendous diversity, much of which has been exploited by humans. Among the examples given are antibiotics produced by some microorganisms, clinical and recreational drugs, dyes and compounds used in the fight against cancer. It is clear that the biological world contains large numbers of molecules that can be valuable commercially and in health care and this is one obvious reason to protect the planet’s biodiversity. Biologists are rather fond of quoting Dobzhansky’s (1973) statement that ‘Nothing in biology makes sense except in the light of evolution’. This can sound rather glib but, while compiling this article, I have been struck by the fact that diversity in biological molecules is so directly related to the natural selective pressures on them, or on parts of them, that one cannot sensibly proceed without addressing this situation at the outset. Darwin eloquently reviewed the processes by which the fittest individuals tended to survive although he knew nothing of biochemistry or genetics. A core concept here is that those forms of molecules that do not contribute effectively to the survival of individuals and the production of offspring will tend to be lost during evolution in favour of those that function more efficiently. The relationship between the intensity of selective pressure and patterns of diversification that have survived in the proteins of extant species will be considered using trypsin as a case study. A quite different context for the consideration of molecular diversity in nature is the opportunities for exploitation that it offers to humans. We know something of the remarkable range of natural molecular resources available to us for use in medicine and various commercial processes and some of these are reviewed here. However, there must be myriads of other valuable natural molecules that have not yet been characterised. In itself, this should represent a strong reason for striving to conserve the natural world. The basic structure of DNA, RNA and proteins There is hardly any variation in the structures and processes by which genetic information is stored and read to control the growth, development, metabolism and reproduction of different organisms. The structure of DNA is well known, with its double helix, its sugarphosphate backbone and, critically, four bases that carry genetic information that is inherited by the next generation. Other than the order of the bases in different genes, this structure is identical across bacteria, plants, fungi and animals. About 50 years ago, biologists were unravelling the SSR March 2010, 91(336) 33 Diversity in biological molecules genetic code in the bacterium Escherichia coli. Since then it has become clear that the triplets of bases in DNA that define amino acids along the primary sequence of a protein are the same in the genomes of all living organisms. What better evidence could one have to demonstrate a common origin of all life on Earth? Actually, one finds slight variations in the genetic code within the mitochondrial genomes of plants and fungi, so that the use of the term ‘universal genetic code’ is a slight exaggeration; however, the endosymbiont origins of mitochondria must have occurred very early in the evolutionary history of eukaryotes and the variation we can see must have similarly early evolutionary roots. Against this background of near uniformity in information storage, inheritance and processing, one must look at individual genes, the proteins they encode, and the enzymic and regulatory functions that they perform, to encounter the diversity that is the subject of this article. Variation in sequence data allows us to follow the evolutionary past Recent technical advances have allowed the sequencing of genes and proteins, leading to enormous amounts of nucleotide and amino acid data held in openly available international databases. These can be accessed using freely available software such as Entrez: The Life Sciences Search Engine (see Websites) where one can move to the Protein Sequence Database and search for the amino acid sequence of a particular protein in a particular species. This is provided in a format where each amino acid is represented by a single letter code; this will not be familiar to all users but a key for the designations can easily be found using the Web. Having obtained the sequence of a particular protein from one species, one can obtain that protein sequence for a series of other species that are less and less closely related to the initial organism. This provides a data set that allows one not only to examine relationships between living species, but also to reconstruct the evolutionary past of a group of organisms. Protein sequence data are particularly useful in this context since one can fairly easily select a protein that is made by a very wide range of organisms. This allows comparisons to be made between organisms as widely separated as apes, barnacles and finches (to use a few examples that were considered in detail by Darwin). 34 SSR March 2010, 91(336) Newbury It is difficult to make comparisons between such groups using morphological characters but they all contain homologous proteins that are simple to compare because they are all linear structures and every position in them is occupied by one of 20 amino acids. Comparisons of such structures lend themselves to computer analysis, and freely available software such as ClustalW2 (see Websites) can be used to line up a series of protein sequences to show which ones are most similar and, interestingly, whether the sequence of some parts of the protein is more highly conserved across species than other parts. Although an interested non-expert (including a school pupil) can carry out these analyses, there would inevitably be teething problems associated with formatting the data before analysis by the software packages. Because of this, I have compiled sets of instructions and correctly formatted data on a University of Worcester website (see Websites). The protein selected for use is trypsin, on the basis that most people have heard of it and that we know a lot about the way that its structure relates to its function – which is of interest later. Figure 1 shows the result of aligning the central region of the amino acid sequence of trypsin from a range of different animal species. The first message here is that the software has been able to align the trypsin sequences even though some of the organisms diverged hundreds of millions of years ago. A second key point is that some parts of the sequences are identical across all of the species (see asterisks). To evolutionary biologists, it is axiomatic that where a molecule plays a role that is critical for the function of a cell, and hence the survival of an individual, one tends to find little variation in its structure across different species. What we are seeing in the trypsin sequence alignment is an extension of this concept. The data suggest that some parts of the trypsin molecule are more critical for its function than others. If we now investigate the way in which trypsin works, we have to consider the way that the protein folds and forms its active site. The latter is the region that binds the enzyme’s substrate (a particular part of another protein which is then cleaved) that, obviously, is the most important part of trypsin when one is considering its function. Information on trypsin’s active site can easily be obtained (e.g. through Wikipedia and elsewhere) Newbury Diversity in biological molecules Figure 1 The result of aligning the central region of the amino acid sequence of trypsin from a range of different animal species using the software ClustalW2 and one discovers that the substrate binds to three amino acids: a histidine (H), an aspartic acid (D) and a serine (S) residue. These key amino acids (arrowed), and others close to them that hold them in place (marked by boxes), are the ones that are identical across the different species. Other parts of the sequences vary and, if one looks at any short region of the ‘variable’ sequences, one can see that the sequences are more similar in closely related species (for example, across the mammals). Whilst one can detect some of these relationships, it is not possible for the human brain to collate all the information in a meaningful way. Once again, this is just the sort of large mechanistic process with which computer software can help us. Experts in bioinformatics have produced packages that can reconstruct an evolutionary (phylogenetic) tree using sequence data. The explanation of how this is achieved for a newcomer comprises a couple of central points. First, the software assumes that any two sequences have evolved from a common ancestor, and it develops a tree that attempts to follow the course of evolutionary history for the group of species by collating the patterns of common ancestry across all the species. Secondly, the software assumes that the simplest explanation for the changes that have occurred between the proposed common ancestors and modern species is correct. For example, it assumes that any change in an amino acid between species/ancestors occurred just once and that there have not been several intermediate changes. This ‘Occam’s Razor’ approach uses the most ‘parsimonious’ process and, like all treatments of biological data, can be challenged. However, it is quite clear that when one uses this general methodology for sets of species for which traditional methods have established a clear evolutionary relationship, one develops similar phylogenetic trees using these sequence-handling packages. One can apply one of the most commonly used (and again freely available) phylogenetic SSR March 2010, 91(336) 35 Diversity in biological molecules packages using the aligned trypsin sequences that we have been considering. The Phylip software (see Websites) is used by professional molecular biologists and, again, formatted trypsin data for this package can be found on the University of Worcester website; Figure 2 shows some of the formatted data. If the aligned data shown in Figure 2 is loaded, the Phylip software proposes the evolutionary tree shown in Figure 3. The tree produced by Phylip is broadly in line with expectations, with the vertebrates separated from the two insects and human and monkey being closely related. However, it is not entirely consistent with standard phylogenies since it suggests that a snake is as closely related to a cow as the latter is to a group of other mammals. Why is this? First, no evolutionary biologist would use one section of one protein to construct an evolutionary tree of this type; the sensible course is to increase the sample size by collating information from a set of different proteins. Secondly, in spite of the reasons given for using trypsin as an example in teaching, it is not ideal for the purposes of defining evolutionary patterns. The Phylip software assumes the most parsimonious explanations for sequence changes are correct and this assumption can be violated for nuclear genes on non-sex chromosomes in diploid organisms. The software does not account for the sudden mixing of sequences that can occur during the infrequent recombination events that might occur within a gene during millions of years of evolution. For this reason, scientists who are following evolution using sequence data usually use proteins encoded by genes within the mitochondrial genome or on sex chromosomes (the human Y chromosome); in both cases, recombination does not occur. Newbury Variation in proteins that control development and adaptation Because individual organisms almost always grow and develop in a consistent and predictable way we tend to take this process for granted. In fact, development is a tightly controlled process and for a variety of ‘model organisms’ it has been possible to identify the proteins that are responsible for this regulation. Because consistent development is so critical to the ‘fitness’ of an individual, one would expect these proteins to be under very strong selective pressure within a species; one does not find significant variation in these ‘developmental genes’ across individuals of a species. However, one of the most striking findings of the last two decades has been that there is very little variation between the sequences of equivalent regulatory proteins in different animal species. Homeobox genes (Hox genes) act to control the expression of other developmental genes and it has been discovered that organisms that shared a common Figure 3 The evolutionary tree proposed by the Phylip software when the aligned data shown in Figure 2 is loaded Figure 2 Formatted trypsin data from the University of Worcester website 36 SSR March 2010, 91(336) Newbury evolutionary ancestor hundreds of millions of years ago (e.g. fruit flies and humans) use the same genes to control the development of their embryos. The slight variations in the structures and timing of production of these developmental proteins have led to the diversification of body plans into the morphologies that we know today. This field of study, showing associations between the structures of key proteins, the processes of development of different organisms, and the reconstruction of our evolutionary past, has been given the popular name of ‘evo-devo’, meaning ‘evolutionary development’. Other articles in this issue are considering variation at the level of individual organisms within a species and the concepts of adaptation and selection on the basis of the survival of the fittest. To be of any significance in evolutionary terms, the adaptations that we can observe have to be heritable. A modern evolutionary scientist has an understanding that the fitness of individuals is based upon the forms of genes that they carry and the relative benefits that they, and the proteins they encode, confer in a particular environmental situation. It is relatively easy to demonstrate the ‘adaptive value’ of genes in bacteria. Antibiotics kill bacteria by binding to specific molecules (typically proteins) and preventing those proteins doing their jobs within the cell. Resistance to antibiotics can occur if a ‘target protein’ can change its sequence in such a way that it can still carry out its cellular function but is sufficiently different to prevent the antibiotic binding to it; alternatively, a bacterium may possess a protein that is capable of inactivating an antibiotic as it enters the cell. We can plate out a mixture of bacteria in a Petri dish and show that only those carrying an antibiotic resistance gene survive when the antibiotic is introduced. This is the survival of the fittest in an environment where the greatest selective pressure is on the ability to grow in the presence of a particular toxic chemical. The same thing happens in a less visible way in the human gut when we are prescribed antibiotics. It is the variation in the genes and proteins that can confer antibiotic resistance that determines whether each bacterium lives or dies and one can unequivocally identify the proteins that are the subject of the selective pressure in such experiments. The ease with which such experiments can be carried out on agar plates Diversity in biological molecules is one of the reasons that bacteria are used as experimental models. Antibiotics are produced by organisms to defend themselves from bacteria in nature. However, in these compelling experiments the selection can hardly be called ‘natural’ since it has been imposed by a human experimenter. Although significant progress is being made, it remains very difficult to identify the key differences between proteins that have adaptive significance in eukaryotic organisms in the natural environment. If we take a familiar example, we can assess some of the progress that is being made. Charles Darwin collected specimens of various finches when he visited the Galapagos Islands in 1835. He eventually realised that the many current finches had evolved from a single species that originally colonised one of the volcanic islands. The different finches have beaks that are adapted for the exploitation of different foods; among the seed eaters the sturdier beaks allow the birds to break into large, tough seeds, while the finer beaks are better adapted or foraging for small seeds (Figure 4). Recent studies have shown that extreme weather events on particular islands have a large effect on the availability of different sorts of seeds and that this has a marked influence on the size of the populations of individual finch species. Clearly the beaks are under strong selective pressure, but which genes and proteins vary to produce birds with differing beaks? It has become possible to identify some genes involved in controlling ‘craniofacial’ development in vertebrates: that is, development in the area Figure 4 One of the many species of Galapagos finch whose beaks have evolved to exploit different food sources SSR March 2010, 91(336) 37 Diversity in biological molecules where birds produce beaks. One of these is called Bmp4. When chicken embryos were genetically engineered so that they expressed Bmp4 more strongly, they produced embryos containing extra Bmp4 protein and which later possessed wider and deeper beaks. In a parallel set of experiments, a gene controlling beak length (a calmodulin gene) has been found. Once again, genetically engineering chick embryos expressing the calmodulin gene more strongly led to longer beaks. On the basis of these experiments, it has been suggested that differing forms of these genes/proteins may be responsible for the differing beak shapes and sizes in the Galapagos finches and may be the molecules that are under direct selective pressure by the environment on the islands. The researchers involved in these studies are careful not be more definite in their conclusions because they are aware that the genetic variation in the finches may turn out to lie in proteins that control the rate of synthesis of Bmp4 and the calmodulin proteins rather than in those two proteins themselves. Newbury With regard to plants, the study of molecular diversity has been recognised as ‘phytochemistry’, and the variation in secondary metabolism and the compounds produced have been used to help classify genera into families. This activity has been largely overtaken by the use of DNA and protein sequence data; however, there are some simple informative examples involving familiar plants. One of the most obvious is the mint family, members of which tend to share a set of genes that encode enzymes which act in pathways leading to the production of various essential oils. These may act to deter herbivores (probably chiefly insects) in nature, but have been seized on by humans for their aromatic qualities. Most people will be familiar with the odours produced by mint (Figure 5), basil, Variation in metabolism and metabolic products The core processes of primary metabolism (such as glycolysis and the tricarboxylic acid pathway) are consistent across all organisms in terms of the initial substrates, the intermediate compounds, and the ultimate products of the pathways. One can argue that this is further evidence that all organisms had a common origin. However, one should also take into account the fact that the thermodynamic constraints on metabolic processes will mean that there are only a limited number of possible chemical pathways that could exist with regard to the storage and release of energy from simple carbon-based compounds. If one moves away from these core metabolic processes, one starts to see diversity across organisms. For example, different groups of organisms make different polymers of glucose units which then serve different functions. The diversity, which is based upon the type of linkage between the repeating units and the branching characteristics of the chain, results in polysaccharides with diverse functions such as starch, cellulose and glycogen. These are differences that exist between plants and animals, but one can easily find diversity at lower taxonomic levels. 38 SSR March 2010, 91(336) Figure 5 Mint, and the familiar scented herbs, basil, rosemary, thyme, lavender, sage, oregano and marjoram, all belong to the same family, members of which tend to share a set of genes that encode enzymes which act in pathways leading to the production of various essential oils (photo, Victoriana Nursery Gardens www.victoriananursery.co.uk) Newbury rosemary, thyme, lavender, sage, oregano and marjoram, but may not be aware that they are all members of the same family. Some of the diversity in natural molecules has direct implications for human and animal diets. There is diversity with regard to the major fatty acids synthesised by different organisms, with repercussions on human health. For example, lard and butter contain 38–48% of the saturated stearic and palmitic fatty acids while soybean, peanut and olive oils contain only 10–11% of these compounds and much larger proportions of the unsaturated fatty acids (such as oleic and linoleic acids). Variation in amino acid content in plants that we use as food can also be important. Plants and microorganisms can synthesise all the 20 amino acids that are components of proteins, whereas mammals can only make 12 of these. Clearly plants and microorganisms possess some metabolic pathways that mammals do not. A consequence of this is that mammals require eight ‘essential’ amino acids as part of their diet. This is not a problem for carnivores but is something that can pose problems in some agricultural situations. For example, if one is fattening pigs one cannot feed them only on a diet of barley grain – a relatively cheap commodity. Pigs fed solely on barley do not ‘thrive’ because the grain contains very low levels of lysine, which is an essential amino acid. Plants store amino acids in seeds as insoluble ‘storage proteins’. The selective pressure on storage proteins is to ensure that they can fold tightly and occupy a small amount of space. The exact amino acid content is of little importance since when they are broken down during germination the seedling has the metabolic pathways to inter-convert amino acids and produce the full range needed for the synthesis of new proteins. The family of storage proteins in barley (the ‘hordeins’) contain very low levels of lysine. Because of this, intensive pig fattening requires the supplementation of barley with other feedstuffs, such as the more expensive soybean meal that contains an adequate level of lysine and other amino acids. The brief discussion of the relevance of diversity in the types and relative amounts of different metabolites in harvested plant organs naturally leads us into a broader discussion of the exploitation of this diversity by humans. This is a very large subject and the selection of the few examples considered here is based upon their social and cultural contexts with no pretence at a comprehensive review. Diversity in biological molecules The microbial world is an enormous resource for human technology and it might be useful to select a few of the specific compounds that are produced by microorganisms and that contribute to human health. Most people have heard about the discovery of penicillin, which proved to be a very effective treatment for certain bacterial diseases, such as syphilis and Staphylococcus infections. The major advance was the development of the concept that certain microorganisms produce compounds that kill other microorganisms. Fungi (such as Penicillium) and bacteria produce a range of strange compounds and some of these are powerful antibiotics (Figure 6). The Streptomycetes, a bacterial group, possess complex secondary metabolism and produce around 70% of the clinically useful antibiotics that are of natural origin. This is a prime example of molecular diversification that has benefited mankind, with the list of antibiotics Figure 6 Fungi (such as Penicillium chrysogenum shown here) and bacteria produce a range of strange compounds, some of which are powerful antibiotics providing very effective treatment for certain bacterial diseases (scanning electron micrograph of spore head showing the chains of conidia, www.misac.org.uk) SSR March 2010, 91(336) 39 Diversity in biological molecules from Streptomyces species including streptomycin, cycloheximide, chloramphenicol, tetracycline, puromycin and kanamycin. As some clinically important bacteria have developed resistance to most of these, and other, antibiotics (as in the case of MRSA), clinicians have turned to newer compounds such as vancomycin, which is produced by a member of another group of bacteria called the Actinobacteria. This is said to have been isolated by a drug company from a soil sample collected in Borneo. As some infectious bacteria have started to develop resistance to vancomycin, even newer antibiotics, such as daptomycin, are being employed. Again, this new compound was isolated from a soil-living Streptomyces species. One should not ignore the very significant advances being made in the design of synthetic compounds that can act to kill human pathogens; however, the molecular diversity that exists within certain groups of microbes has made an enormous contribution to human health. Diversity in biological molecules has also been exploited by humans in their search for dyes for fabrics. Once again, these natural compounds are being replaced by synthetic chemicals, but the social history associated with natural colouring compounds can be fascinating. One of the few natural sources of red dye is cochineal, which is derived from a group of scale insect species that produce carmine (Figure 7). These Dactylopius species occur in tropical and subtropical regions of America and were used by the Maya and Aztec people. The insects live on species of the Opuntia (prickly pear) cactus and have to be gathered by hand (Figure 8). In Britain, carmine was one of the dyes used to produce the army’s famous red coats; also used for this purpose was the British plant Rubia tinctorum or common madder (Figure 9), which produces a dye of the same name. Purple dyes have historically been very valuable and in Greek and Roman times the ultimate rulers wore purple clothes. Tyrian purple (or imperial purple) was originally extracted from a mucous secretion of the marine snail Murex brandaris (= Haustellum brandaris) (Figure 10). The Phoenicians were the first to produce the dye and it is said to have been a major reason for their wealth. The blue/purple dye is now known as indigo and is also synthesised by several plants. Most of the natural indigo is now produced by the genus Indigofera which is native to the tropics. 40 SSR March 2010, 91(336) Newbury Figure 7 A cluster of female Dactylopius coccus or cochineal, the scale insects that are the source of the red dye carmine, growing in La Palma, Canary Islands (photo, Frank Vincentz GFDL) Figure 8 Cochineal (the white patches) on cacti in La Palma (photo, M. Violante GDFL/CC-BY 2.5) Figure 9 Common madder (Rubia tinctorum), another source of natural red dye Newbury Figure 10 Murex brandaris (= Haustellum brandaris), a marine snail from which the Phoenicians extracted the purple dye, Tyrian purple, which was used to colour the clothes of the ruling classes Figure 11 A capsule of the opium poppy Papaver somniferum showing latex (opium) exuding from an incision Diversity in biological molecules However, in Britain it has also been extracted from woad (Isatis tinctoria). A further class of diverse exploitable compounds are ‘bioactive’ substances that have served as both therapeutic and recreational drugs. A large proportion of these have been derived from plants and there are far too many to present a comprehensive review here. Instead, a selection of substances known as ‘alkaloids’ (ring structures which contain basic nitrogen atoms) will be presented to provide a snapshot of the molecular diversity available for exploitation. The alkaloid, caffeine, is probably the most widely consumed psychoactive substance in the world; with its stimulant properties it is found as a component of tea and the South American drink, mate, as well as coffee. Nicotine is another alkaloid stimulant and, like caffeine, probably acts to deter insect feeding in nature. Both of these are legal compounds, but many alkaloids are the active components of ‘recreational drugs’. The opium poppy Papaver somniferum is the source of the well-known substances heroin, morphine and codeine and all of these have been prescribed by clinicians as powerful painkillers (Figure 11). If one considers heroin alone, recreational users speak of the ‘rush’ that it gives them along with a feeling of euphoria; the chemical processes within the brain associated with these feelings are partly understood. The major problem with heroin use is its addictive nature (consider also nicotine) and one could argue that this particular property has caused one of the world’s biggest social problems. Cocaine is another alkaloid and is extracted from the leaves of the coca plant (Erythroxylon coca). It can act as a stimulant and to suppress hunger and was used medically to provide pain relief, even being used as a local anaesthetic. It was freely available in the late nineteenth century and was even a component of the original (but not the current) recipe for Coca Cola. A further, famous alkaloid is quinine, which is extracted from the bark of the cinchona tree and was the first effective treatment against the malaria-causing protozoan Plasmodium falciparum. A common theme with these therapeutic compounds is an initial observation by western visitors of the use of local plants by native people, the later isolation of the active ingredient and its commercialisation and, more recently, the chemical synthesis of the same or SSR March 2010, 91(336) 41 Diversity in biological molecules Newbury similar compounds for medical use. This process is still occurring. There is an active debate about the legal rights that native people should have to their knowledge and the ‘genetic resources’ of the plants in their countries, with occasional claims of ‘biopiracy’ made against companies that make a profit from their acquisition. While for many people the conservation of the natural world is sensible behaviour that requires no explicit justification, others ask for the economic benefits of the protection of species and habitats. Perhaps a consideration of an obscure Madagascan bush might serve to help them appreciate the enormous potential benefits of unstudied and apparently useless species. The existence of the Madagascan periwinkle Vinca rosea (= Catharanthus roseus), like tens of thousands of other species, is under threat – in this case chiefly because of slash-and-burn agricultural techniques. Had it become extinct before its potential pharmaceutical value had been investigated, we would not have available the alkaloids vincristine and vinblastine, which act to inhibit the division of cells by binding to the spindle structure. This characteristic means that these compounds are of tremendous benefit as anti-cancer drugs, cancers being composed of cells that divide in an uncontrolled manner within the body. The compounds are used as part of mixtures to treat lymphatic cancers. For example, vincristine is a component of CHOP, widely used in chemotherapy for non-Hodgkin’s lymphoma, whilst vinblastine is part of ABVD, which is a chemotherapy treatment for Hodgkin’s lymphoma. The latter is one of only a few cancers that, even in the later stages, now have a very high cure rate. The Madagascan periwinkle is a plant whose value we have identified; how many more organisms that have not received the same attention also have benefits to humans? If we allow them to become extinct, we will never know. Molecular diversity is fascinating and allows us to analyse the evolutionary past of the biological world. However, it also provides valuable resources for mankind and is likely to do so for many years to come. References Websites Darwin, C. (1859) The origin of species by means of natural selection. London: Murray. Dobzhansky, T. (1973) Nothing in biology makes sense except in the light of evolution. American Biology Teacher, 35, 125–129. ClustalW2 (EBI): www.ebi.ac.uk/Tools/clustalw2/index. html Entrez, the Life Sciences Search Engine (NCBI): www.ncbi. nlm.nih.gov/sites/gquery Phylip: www.phylip.com University of Worcester sites for teaching notes and sequence data prepared by H. J. Newbury to support protein sequence alignment and development of phylogenetic trees using trypsin data: www.worc.ac.uk/ documents/Teaching_notes_(2).pdf and www.worc.ac.uk/ documents/phylip_data.pdf Professor H. John Newbury is head of the Institute of Science and the Environment, University of Worcester. Email: [email protected] 42 SSR March 2010, 91(336)