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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
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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).
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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
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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
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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
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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.
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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)
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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.
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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)
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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]
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SSR March 2010, 91(336)