Hitch-hiking DNA – a guide

This essay was written by Iain Wilson and was first published in the 1997 Mill Hill Essays.

Diagrams of trees, with branches, nodes, and even roots, are often used to represent the evolutionary relationships between organisms, or for that matter between sets of genes. Refining these “trees of life” is a very active area of research and adventurous scientists, like their butterfly-hunting predecessors in the not so distant past, plumb the depths of the oceans and explore the worldís hot-springs in the search for our primaeval ancestors. Nowadays, sophisticated statistical analyses are made, using packages of refined computer programmes, of the different sequences in which the building blocks of DNA from these new-found organisms are arranged. On this basis the organisms are then placed like leaves on the tree, but in the order of their DNA sequence inter-relationships. Despite the clear depictions of evolution that emerge from this imposed statistical framework, there is still much controversy in the detail and it has become clear that some blurring of the generally clear bush-like structure of “the tree” has to be accommodated into the picture. This is because some shoots emerging from different main branches have been found to touch each other – as if blown in the winds of evolution. Their points of contact form a network within the tree indicating that exchanges of genes have occurred between organisms, by processes that have important evolutionary consequences.

Prime examples of these exchanges, long known to biologists, involve two vital cellular compartments or organelles known as the mitochondrion and the chloroplast. Both types of organelle are involved in energy generation and are actually derived from bacterial cells that have been “captured” by another cell and subsequently incorporated into it through a process known as endosymbiosis. In the course of evolution, the captives have become stripped-down versions of their former selves and genetically dependent on their hosts. There are many mitochondria in most human cells, and biochemical studies, confirmed by research into molecular evolution, have shown that these organelles derive from a member of one group of bacteria. By contrast the chloroplasts which manufacture and carry the pigments characteristic of plant cells, originate from a green bacterium. Indeed, plant cells contain both mitochondria and chloroplasts, the latter being acquired from a later endosymbiotic event, so that plants are the only higher organisms with three DNA-containing compartments.

Detailed examination of these two kinds of organelle has revealed a great diversity of content and function, so biologists have questioned the number of times that such transfers have happened. Are all mitochondria and chloroplasts that we find today derived from single endosymbiotic events that happened long ago, or could there have been numerous events? The evidence increasingly points in both cases, to single events. A by-product of all this work has been the finding that there is a flow of genetic information between the compartments in the cell, the host cell nucleus acting as “the great attractor” – to borrow an astronomical analogy. Certain genes found in the nucleus of what are commonly called “higher” forms of life have in fact originated from the organelles of primitive bacterial cells. Genes have also exchanged between the organelles themselves. Such revelations have given students of evolution cause for thought, raising searching questions about the exact origins of the genes they compare in the construction of their trees of genetic relatedness.

The incorporation of lower cells into higher cells with subsequent integration of both life forms into a kind of chimaeric organism, gives a dynamic picture of evolution at the whole cell level. Equally fascinating has been the realisation that secondary as well as primary acquisition of organelles can occur between “higher” cells. This seems to have been particularly the case with chloroplasts. In recent years, work on a number of single-celled “plants” or algae has revealed that some of them contain organelles that have not come directly from bacterial sources but by the endosymbiosis of another entire algal cell! In the single-cell world it is not at all uncommon to find organisms that have taken up other cells and formed temporary symbiotic relationships with them. But in the particular case of secondary endosymbiosis the incorporated algae seem to have stabilised in an intermediate state between an organelle, like a mitochondrion or a chloroplast, and an independent cell. Thus, as well as their own chloroplast and their other cellular components, these captives have retained a portion of their own genome in a tiny nucleus and transferred the remainder of it to the nucleus of their host. These tiny nuclei carry the smallest known genome of a higher organism on three minute chromosomes.

At present only a few instances are known of symbionts in this intermediate state, far greater numbers have progressed past this point. In such cases, the host cells retain just the chloroplast, “on permanent loan” as it were from the original algal endosymbiont which otherwise has disappeared – but not genetically!! Its genes have hitch-hiked a ride in the host cellís nucleus from where they make sure that the chloroplast is retained. Examples include such important organisms as the toxic marine algae that give rise to the red tides, the so-called “algal blooms” that can decimate shellfish industries, and surprisingly enough, the human malaria parasite!

It has come as a shock to botanists to learn that such an important human pathogen as malaria still carries traces of a photosynthetic past and falls into their province. Parasitologists, on the other hand, have been somewhat bemused to see one of their star organisms in terms of its infamous reputation don a coat of a different colour! This change of outlook on the biological status of the malaria parasite has emerged from a study of what was thought to be the mitochondrial DNA of the parasite. Detailed study of this DNA sequence eventually made its mitochondrial origin seem more and more unlikely, until at last a number of genes were identified that are characteristic of chloroplasts! Gradually it has emerged that malaria, as well as several other important parasites, carry three kinds of DNA just like plants.

The entire chloroplast-like DNA of the most virulent of the human malaria parasites has now been characterised and most of the genes that it carries have been identified. It bears a remarkable general resemblance to DNA from a small selection of non-green, parasitic flowering plants. These plants have “forgotten” how to photosynthesize, and like them all the malarial genes originally dedicated to photosynthetic machinery have been lost. However this process of degeneration, or perhaps more correctly specialisation, has gone further in malaria than in any other known chloroplast-like genome. Why it has not disappeared completely remains unknown, but the implication is that the remaining DNA still has a function that the parasite needs.

So how did the malaria parasite get this DNA and what organelle carries it? We have come to believe that it has an algal origin rather than being derived either directly from a bacterium or secondarily from a higher plant. Algal chloroplast-like organelles captured by secondary endosymbiosis are bounded by several membranes and the hunt for such an organelle in the parasite did not have far to go since an enveloped structure of this sort had been noted decades ago but had languished unattributed since then. By probing the parasite for its chloroplast-like DNA its presence in this multi-membraned organelle was demonstrated but important details, such as the exact identification of the algal source, remain to tease the investigators exploring this issue. Equally importantly, two other related pathogens, Toxoplasma, that can cause devastating generalised damage to the brains, hearts and livers of AIDS patients and Eimeria, a major cause of intestinal infections in chickens, have also been found to carry similar chloroplast-like DNAs. This again strongly suggests that these DNAs have been retained because they perform a vital function, and raises the obvious question “could this function represent a target that new drugs might attack?”.

Two parallel lines of investigation address this issue. One of the genes found on the malarial chloroplast-like DNA has a counterpart in certain bacteria. When this gene is removed from the bacteria the effects are disastrous, so this gene at least seems to be essential. The second and more wide-open approach is to start looking for algal genes that are hitch-hiking in the parasite’s nucleus. These may include genes for the specialised chloroplast-like processes undertaken in the organelles such as the synthesis of fatty acids and essential amino acids. As with many other organisms, whole nuclear genome sequencing projects for malaria and toxoplasma are well under way in several laboratories around the world. Quite soon, someone will find a DNA sequence that will reveal its chloroplast antecedents. This could provide the key to unlock a whole system of enzymes that malaria has retained by a kind of genetic frugality – never mind if a gene is secondhand, if it does something useful it is likely to be kept rather than discarded.

Interactions leading to genetic exchange between organisms offer a range of opportunities in addition to the gradual processes of evolution. The natural world has not allowed such opportunites to pass by without exploiting them and it appears that the progenitor of malaria parasites took the opportunity to make such a smash-and-grab raid on a photosynthetic cell in the long distant past. What is really interesting is that they have maintained at least the basic elements of a chloroplast-like organelle for an extremely long evolutionary period estimated to be in the order of 800 million years. This can only mean that the organelle has a function and the race is now on to discover what it is in the hope that we in turn can exploit it for our own benefit!

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