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Cheetah genetic diversity revisited Hilary Miller Feb 04

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ResearchBlogging.org

Another chapter has been added to the story of genetic variation in the cheetah, with a paper out in next month’s Molecular Biology and Evolution journal giving a detailed description of variation at key immune genes in the species.  I first became familiar with the cheetah story as a PhD student when I was studying genetic diversity in the black robin.  At the time the cheetah was something of a poster child for the perils of low genetic variation, but this most recent paper suggests that their immune system is not as genetically invariant as first thought, and they may not be so vulnerable to disease after all.

Back in 1985, Stephen O’Brien and colleagues at the National Cancer Institute in Maryland reported extremely low levels of genetic variation in cheetahs - so low in fact, that skin grafts from one animal were not rejected by another, a sign that their immune systems are genetically identical.  This lack of genetic variation was attributed to a decline in population numbers at end of last ice age, plus more recent declines that have led to inbreeding.  The species appeared to be highly susceptible to feline infectious peritonitis (FIP), a disease which had decimated some captive populations, and attempts to breed cheetahs in captivity were hampered by poor reproductive success and apparently high levels of sperm defects.  O’Brien and colleagues attributed these problems to their extremely low levels of genetic variation, and the species quickly became a classic example of the perils of inbreeding. 

The cheetah (Acinonyx jubatus) is found mainly in southern and eastern Africa

However, in the early 1990′s, field studies questioned whether the cheetah’s survival in the wild was being compromised by their lack of genetic variation.  In a commentary in Science in 1994, Caro and Laurenson pointed out that disease susceptibility and breeding problems only appeared to be an issue for captive cheetahs, and that predation of cubs, habitat destruction and persecution by humans were greater threats to the species.

Still, a lack of variation at immune genes is still an important potential threat to any species, as shown by the case of the Tasmanian devil, where low variation at Major Histocompatibility Complex, or MHC genes, has allowed Devil Facial Tumour Disease to spread unchecked throughout the population.  MHC genes are key part of the immune system in vertebrates as they code for the molecules that distinguish self from non-self, and instruct the immune system to respond when foreign proteins (i.e. from a pathogen) are detected.  High diversity at MHC genes plays an important role in protecting populations from disease epidemics as it allows wide array of foreign pathogens to be resisted, and means that some individuals are likely to be more resistant to new diseases than others (instead of all individuals being equally susceptible).  

The skin graft experiments of the mid-1980s indicated that cheetahs have virtually no MHC variation, because of the absence of an immune response when skin from one cheetah was grafted onto another.  However the disease susceptibility seen in captive cheetahs doesn’t seem to extend to cheetahs in the wild – a recent study on wild cheetahs in Namibia  found that the population was generally in good health, and that many individuals carried antibodies to a range of diseases (suggesting they had been exposed to those diseases) but no clinical symptoms of acute disease.  These results suggest that wild cheetahs may have more MHC diversity than the captive population, and that their immune systems work just fine. 

Somewhat surprisingly, only a couple of studies in the 26 years since the skin-graft study was published have actually attempted to quantify cheetah MHC diversity.  These studies found low diversity and seemed to corroborate the skin-graft results, but either used low resolution methods to measure MHC diversity or had small sample sizes, so weren’t particularly conclusive.

This latest study, by Aines Castro-Prieto, Simone Sommer and colleagues at the Leibniz Institute for Zoo and Wildlife Research in Berlin, takes a much more comprehensive approach to measuring genetic variation.  Castro-Prieto and colleagues determined how many different alleles are present at two types of MHC genes in 149 Namibian cheetahs.  They found more variation than was previously described for the first type (Class I MHC), but not for the second type of gene (Class II MHC).  The number of different MHC alleles counted in the Namibian cheetahs is still quite low compared with what is seen in other big cat populations, so it appears that cheetahs have lost a fair amount of variation as their numbers have declined.  However, the amount of DNA sequence variation among the alleles is fairly high - that is the different alleles code for proteins that are quite different from one another in their sequence, so overall they can probably recognise a wide array of foreign proteins. 

Castro-Prieto and colleagues also found hallmarks of selection on the MHC sequences, and speculate that selection, driven by exposure to a range of pathogens over thousands of generations, has led to highly divergent alleles being retained.  However, they point out that although wild cheetahs appear to have enough MHC variation to respond to common infectious diseases, they may still be at risk from new emerging diseases, as the few remaining alleles might not be sufficient to be able to recognise and ward off an entirely new pathogen.   

This study provides some much-needed data on immune variation in cheetahs, and it seems that the idea of the cheetah being a classic case of disease vulnerability associated with low genetic diversity is looking a little shaky.  As Castro-Prieto et al point out, “the long term survival of free-ranging cheetahs in Namibia seems more likely to depend on human-induced rather than genetic factors”.

Reference: Castro-Prieto A, Wachter B, & Sommer S (2010). Cheetah paradigm revisited: MHC diversity in the world’s largest free-ranging population. Molecular biology and evolution PMID: 21183613

Further reading:

For an excellent write-up on why genetic diversity is important (and more stuff about cheetahs), see this (fairly old) post on Mauka to Makai .

O’Brien SJ, Roelke ME, Marker L, Newman A, Winkler CA, Meltzer D, Colly L, Evermann JF, Bush M, Wildt DE (1985) Genetic basis for species vulnerability in the cheetah. Science 227: 1428-1434

Caro TM, Laurenson MK (1994) Ecological and genetic factors in conservation: a cautionary tale. Science 263: 485-486.

Thalwitzer S, Wachter B, Robert N, Wibbelt G, Muller T, Lonzer J, Meli ML, Bay G, Hofer H, Lutz H (2010) Seroprevalences to Viral Pathogens in Free-Ranging and Captive Cheetahs (Acinonyx jubatus) on Namibian Farmland. Clin. Vaccine Immunol. 17: 232-238.

A simple change determines male vs female organ development in flowers Hilary Miller Oct 30

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ResearchBlogging.org Gene duplication is a  major source of genomic novelty for evolution to work on.  When genes duplicate, the extra copy of the gene is often redundant – it might degrade and become a pseudogene or take on a completely new function.  Alternatively, the function of the original gene might become partitioned between the two duplicates in a process known as subfunctionalization.  An excellent example of this has recently been reported in the genes that control male and female organ development in the flower, and it’s (almost) all down to a single amino acid change between the duplicate genes.

Development of male and female reproductive organs in flowers is controlled largely by a group of genes called MADS-box transcription factors. Different versions of these transcription factors (known as A, B or C function genes) are expressed in different parts of the developing flower, acting either alone or together to produce sepals, petals, stamens (male) or carpels (female)*.

Much of what we know about flower development comes from studies on two “model” plants – Arabidopsis (rockcress) and Antirrhinum (snapdragon).  In these species, and in many other flowering plants, the MADs-box C-function gene that controls the production of carpels vs stamens has duplicated. In Arabidopsis, one of the copies (called AG) makes both male and female organs, but the other copy has taken on the completely new function of making seed pods shatter (and is appropriately called SHATTERPROOF).  However, in Antirrhinum both copies still play a role in sex organ development: one copy (called FAR) makes only male parts, while the other copy (PLE) makes mainly female parts but also has a small role in making male parts.

Thus in Antirrhinum, the function of the original gene (making both male and female parts) has almost been split between the two duplicate copies.  In a study published online in PNAS last week, researchers at the University of Leeds, led by Professor Brendan Davies,  found a surprisingly simple difference in the two copies has led to their profoundly different roles.

Davies and colleagues created chimeric versions of PLE and FAR, swapping domains between the proteins to determine exactly what parts of the different proteins are responsible for their differing function.  They narrowed down the difference between the two genes to a single amino acid that is present in FAR but not in PLE. When this amino acid was removed from FAR, the gene switched to making both female and male parts.  FAR and PLE are estimated to have duplicated around 120 million years ago, and the researchers estimate that the mutation responsible for inserting the extra amino acid into FAR happened around 20 million years after the duplication.

Duplicated genes often take on new functions because changes in their regulatory regions change how and where they are expressed.  Thus, finding an example such as this one, where a simple change in the protein coding sequence causes a profound change in function is somewhat unusual.  However, these proteins don’t act in isolation – they are just one part of a network of genes that must work together to control sex organ development.  Davies and colleagues found that the single amino acid change alters the ability of the protein to interact with other proteins in this network.

The additional amino acid in FAR is found in the part of the protein that interacts with other types of MADs-box proteins called SEP proteins.  C-function genes without the additional amino acid (like PLE) can interact with 3 different SEP proteins (SEP1, SEP2 and SEP3), but proteins with the additional amino acid (like FAR) can only interact with SEP3.  The SEP3 gene is not expressed in the first whorl of the flower, where female parts are produced, so FAR doesn’t have anything to interact with in this whorl and therefore doesn’t produce female parts.

Davies describes this as “an excellent example of how a chance imperfection sparks evolutionary change”.  It is also a nice example of subfunctionalization in action, where a simple amino acid change provides a means of separating the functions of the duplicate copies by causing a change in how the protein operates in a larger regulatory network.

Reference: Airoldi CA, Bergonzi S, & Davies B (2010). Single amino acid change alters the ability to specify male or female organ identity. Proceedings of the National Academy of Sciences of the United States of America PMID: 20956314

*For more on the ABC model of plant development, see here or here.

Origins of the tree of life (re-post) Hilary Miller Aug 27

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The chicken or egg blog family is on holiday in Germany during August, so I probably won’t have a chance to write any new posts.  To keep you all entertained, I’ll be re-posting some of my earlier (pre-Sciblogs) articles. This post is from August 2009.

Darwin is usually credited with being the first person to describe relationships among species as a tree.  I’ll admit I always thought this was the case, until this week when some discussion on an evolution email list I subscribe to enlightened me.

Darwin used this tree figure in The Origin of Species to illustrate his idea of “descent with modification”, with the branches representing the diversity of species all interconnected back through time.

Darwin’s tree of life – the only figure in The Origin of Species.

However, some 50 years earlier, in fact in the year of Darwin’s birth 1809, Jean-Baptiste Lamarck used a tree of sorts to depict evolution in his book Philosophie Zoologique.  Lamarck is best known for wrongly believing that evolution happened by the inheritance of acquired characteristics, but he should be given credit for being the first scientist to develop a theory of evolution – unfortunately he just had the mechanism wrong.

But ideas about trees were around even before Lamarck’s time.  Perhaps the earliest description of a tree of life comes from Russian naturalist Peter Simon Pallas, in 1766:

But the system of organic bodies is best of all represented by an image of a tree which immediately from the root would lead forth out of the most simple plants and animals a double, variously contiguous animal and vegetable trunk; the first of which would proceed from mollusks to fishes, with a large side branch of insects sent out between these, hence to amphibians and at the farthest tip it would sustain the quadrupeds, but below the quadrupeds it would put forth birds as an equally large side branch.

The earliest published tree diagram likely comes from 1801, when French botanist Augustin Augier published his Arbre Botanique, a detailed tree diagram complete with leaves that depicted his view of the relationships between members of the plant kingdom.

Arbre Botanique

Of course the theory of evolution has advanced somewhat since Darwin’s time and we now know that the idea of a tree of life is a little too simplistic.  As explained in a recent article in New Scientist (which was published with the outrageously inflammatory cover “Darwin was wrong” that no doubt excited a few creationists), some species relationships, particularly of the earliest organisms, are better described by a network rather than a tree, which acknowledges that hybridisation and horizontal gene transfer play a big role in evolution.

If you want to read more on the history of the tree of life, have a look at this article by David Archibald from San Diego State University.

3D animation for teaching ecology and evolution Hilary Miller Jul 29

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The Plant Ecology and Evolution group at the University of Vigo in Spain has been making 3D animation videos about their research, which are free to download for teaching purposes.

Here’s a sample of their work, showing how lizards disperse seeds



A full list of their videos is available on their website.

Beating the creationists at their own game? Hilary Miller Jul 21

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ResearchBlogging.org The presence of “gaps” in the fossil record is one of the main arguments creationists use against evolution. The transition from Coelurosaurian dinosaurs to birds is one such purported gap that creationists like to harp on about.  Evolutionary biologists would argue that Archeopteryx fills this gap quite nicely, but this is disputed by creationists, who argue that Archaeopteryx is a true bird and not a transitional form.

A recent study by Phil Senter of Fayetteville State University in North Carolina, published in Journal of Evolutionary Biology, takes another look at the evolution of Coelurosauria but with a twist.  Senter takes on the creationists on their own terms, using a statistical method developed by creationists to visualise morphological gaps in the fossil record, to show that actually, there aren’t any morphological gaps in the fossil record between basal birds (including Archeopteryx) and a range of non-avian dinosaurs.  These findings will come as no great surprise to evolutionary biologists who have long accepted that birds evolved from dinosaurs and that Archaeopteryx has both bird-like and dinosaur-like features.   However, Senter’s rational for doing this study was that if you can demonstrate evolutionary relatedness between species under creationist’s criteria, then they will be obliged to accept the results.

This study is an interesting exercise, but I’m not sure that it really adds a whole lot to the creation vs evolution debate.  Firstly, I’m a little uneasy about the methods he uses. If they are not sound scientific methods, what does it matter what they show?

The methods Senter uses were adapted from the field of baraminology, a branch of creation science in which organisms are classified according to a creationist framework.  Baraminologists believe that each “kind” of organism was created independently and subsequently diversified – and view morphological gaps between taxa as evidence that the taxa were created separately.  Rather than use established methods for measuring  morphological relatedness, the baraminologists seem to have developed their own methods, which don’t seem to be in use outside of the creation science literature.

I’m not a statistician, or a paleontologist, so I don’t know much about these methods, but they seem to be similar to established methods for analyzing multivariate statistics, like principal components analysis and multidimensional scaling.  One of the methods, ANOPA (Analysis of patterns) is even published in a regular scientific journal.  However, a quick search of the Web of Science shows that this paper, published in 2004, has been cited zero times (with the exception of Senter’s paper) suggesting the method hasn’t been picked up by mainstream scientists.  And according to this critique of the method, there are good reasons why not, not the least of which is that there seems to be no statistical basis for identifying discrete groups in the data.  A similar method, that Senter applies to his data is classic multidimensional scaling (CMDS), as implemented in a software program developed by creationist Todd Charles Wood.  Multidimensional scaling is a standard statistical method, but here it uses a creationist measure of “baraminic distances” – which only appears in the creationist literature and isn’t used in standard paleontology.

A second problem with this exercise, is that now that Coelurosaurian dinosaurs and birds have been shown to be morphologically continuous using the creationists criteria, what is to stop the creationists just moving the goalposts and calling Coelurosaurian dinosaurs and birds a single “created kind”?  Also if evolutionary biologists use these method on other groups and find morphological discontinuity, do they then have to accept this as “evidence” for creation?

The problem with the fossil record is that (a) fossilization is rare, so absence of evidence is not evidence of absence, and (b) new fossils are found all the time, so what looks like a gap in the fossil record at one point in time may be filled later on.  Senter demonstrates this really well in his paper, by re-doing the analysis based on what fossils were known at particular time points.  Using this time-series he demonstrates that up until around 2000, there were significant gaps in the fossil record for coelurosaurians.  However, with an explosion of new fossils in the past 10 years, these gaps have all but been filled.  The same is true for many other groups, including basal chordates, bony fishes, turtles etc.  Senter comments in the discussion

the recent explosion in the filling of fossil gaps should give creationists pause, for any such gap-filling is a serious challenge to creation science.

I don’t follow the creation/evolution debate particularly closely so I’d be interested to hear opinions about this paper from those who do.

SENTER, P. (2010). Using creation science to demonstrate evolution: application of a creationist method for visualizing gaps in the fossil record to a phylogenetic study of coelurosaurian dinosaurs Journal of Evolutionary Biology DOI: 10.1111/j.1420-9101.2010.02039.x

Tuatara holds clues to human evolution Hilary Miller Jun 16

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ResearchBlogging.orgA while ago I wrote about the value of genome sequences, not just for helping us understand the biology of a particular organism, but also for enabling large-scale comparisons across species that can help spot patterns in genome evolution which wouldn’t otherwise be apparent.  A recent paper in Journal of Heredity by Craig Lowe, David Haussler and colleagues at the University of California provides an excellent example of this in action, using sequences from the tuatara genome to identify the evolutionary origin of parts of the human genome.

Lowe and colleagues were looking for functional elements (like parts of genes and their regulatory regions) in the human genome that originated from retrotransposon insertions.  Retrotransposons are mobile bits of DNA that have a tendency to make copies of themselves and insert themselves in various different places in the genome.  They contain everything needed for this copying, plus often include functional modules like exons of genes, or transcription factor binding sites.  These functional modules may be co-opted for a new function in the new site, a process known as exaptation.  Once a retrotransposon is inserted in a new location it is often inactivated, and then begins to accumulate mutations which render it unrecognisable as a retrotransposon. This makes it difficult to identify exaptation events in any given genome and hence trace the origin of many of the functional elements of that genome.  However, by comparing the genomes of many different species in different lineages it may be possible to identify ancestral versions of these elements, and so trace their evolutionary history.

Lowe and colleagues found a previously unknown retrotransposon in the small part of the tuatara genome that has been sequenced.  This retrotransposon is of a type known as a LINE – Long Interpersed Nucleotide Element - and was named EDGR-LINE  (endangered-LINE).  A search of human genome against this sequence found 18 elements that are likely to be the result of insertion of this retrotransposon into the genome at some point in evolutionary time.  Seventeen of these elements are gene regulatory regions and one is an exon of a gene called ASXL3.  ASXL3 is important for regulation of other genes during development and the additional exon co-opted from EDGR-LINE appears to help control its expression.

These 18 exaptation events likely occurred early in mammalian evolution, but the retrotransposon itself has long since been inactivated in humans so all traces of it have been lost.  The functional elements it contained are able to be identified because they are under strong purifying selection (i.e. have not accumulated many mutations), so can still be aligned with the tuatara sequence.  Its only through this comparison that it is possible to know that these 18 elements originated from the same retrotransposon.

EDGR-LINE was also found in the lizard, frog, and coelecanth, but no traces of it remain in mammals, crocodylia and birds.  EDGR-LINE appears to be more slowly evolving in tuatara than in lizards, so is closest to the mammalian ancestral version of EDGR-LINE and hence more informative for identifying elements in the human genome. In fact, 10 of the 18 elements could only be identified by comparison with tuatara and not with these other species.

Evolution of the EDGR-LINE in vertebrates. The EDGR-LINE appears to have been introduced in the common ancestor of tetrapods and lobe-finned fish, and lineages where the LINE was active are shown with green. The LINE is not noticeable in mammals, crocodylia, aves, or testudines, so it has already been inactivated at least twice in evolution.

This is not the only example of genomic information from a rare species shedding light on the evolutionary history of human genome.  The genome of the threatened desert tortoise Gopherus agassizii also harbours an ancient LINE that has enabled functional elements of the human genome to be identified.  Lowe and colleagues speculate that this may be due to the very nature of endangered species, and ran simulations to show that theoretically, mobile elements like LINEs are active for longer and evolve more slowly in small populations.   This effect comes about because of the relationship between population size and selection – selection is more efficient in large populations so is more likely to remove genetic variants which are mildly harmful (or deleterious) to the organism, and to fix mutations which are beneficial.  The smaller the population, the more likely it is that deleterious genetic variants will become fixed in that population and beneficial mutations will be removed.  Insertion of mobile elements into new places in the genome is almost always deleterious, as it messes with existing genes and their regulatory regions.  Thus small populations will be more likely to accumulate additional copies of the mobile elements, and less likely to accumulate mutations which would remove or inactivate them.  I should point out here that tuatara are not actually classified as endangered (as the paper claims), but they have had a historically low population size, with probably a severe population bottleneck during the oligocene inundation of the New Zealand land mass.  In addition, we now know that even large tuatara populations can have a small effective population size, as few individuals actually contribute to mating at any one time.

Lowe and colleagues point out that without the tuatara, we would not have been able to identify these particular functional elements in the human genome, and that we never know what additional information about human evolution we might glean from threatened species in the future.  This underscores the importance of projects like the Genome10K initiative to sequence 10,000 vertebrate genomes.  Of course I would add that we should preserve these species for their intrinsic worth not just because of what they can tell us about human evolution, but this paper does highlight the unexpected ways that genomic data from diverse species can help us understand evolution.

Lowe, C., Bejerano, G., Salama, S., & Haussler, D. (2010). Endangered Species Hold Clues to Human Evolution Journal of Heredity DOI: 10.1093/jhered/esq016

An interview with Rebecca Cann of Mitochondrial Eve fame Hilary Miller Jun 01

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In 1987, Rebecca Cann, Mark Stoneking and the late Allan Wilson published a paper in Nature showing that all human females can trace their lineage back to a single maternal ancestor (“mitochondrial Eve“) located in Africa.  In Plos Genetics this week there is an interesting interview with Rebecca Cann, where she talks about her own history and the research behind the mitochondrial Eve hypothesis.

In unearthing the genetic history of human populations, the recent pace of discovery has been so rapid that we can lose sight of the impact made by a single paper. In a 1987 Nature article, Rebecca Cann and her co-workers, Mark Stoneking and the late Allan Wilson, painstakingly analyzed mitochondrial DNA purified from placentas that had been collected from women of many different ancestral origins. By comparing the mitochondrial DNA variants to each other, the authors produced a phylogenetic tree that showed how human mitochondria are all related to each other and, by implication, how all living females, through whom mitochondria are transmitted, are descended from a single maternal ancestor. Not only that, they localized the root of the tree in Africa. The report left a wake, still rippling today, that stimulated not just geneticists and paleo-anthropologists, but the layperson as well, especially as the ancestor was quickly dubbed ’Mitochondrial Eve.’

For the full interview, see Gitschier J (2010) All About Mitochondrial Eve: An Interview with Rebecca Cann. PLoS Genet 6(5): e1000959. doi:10.1371/journal.pgen.1000959

Mammoth hemoglobin back from the dead Hilary Miller May 05

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While we’re on the subject of extinct species, Prof Kevin Campbell and colleagues in Canada and Australia have reported resurrecting mammoth hemoglobin in a paper out this week in Nature Genetics.  This won’t help at all with cloning a mammoth, but provides a fascinating insight into mammoth physiology and evolution.

Hemoglobin is the protein which transports oxygen in the blood.  It is made up of two subunits, alpha and beta globin, which are coded for by two different genes.  Campbell and colleagues used fairly basic molecular biology techniques to isolate these genes from mammoth remains and express the protein in bacterial cells.  Firstly, they amplified both elephant and mammoth hemoglobin genes using PCR and compared their sequences, finding that mammoth beta-globin protein differs from the elephant protein at three amino acid sites.

They then inserted the elephant hemoglobin genes into a bacterial carrier molecule called a plasmid, which had previously been designed to express human hemoglobin.  This carrier molecule basically contains the elephant hemoglobin genes and a bacterial promoter – a little sequence of DNA which is recognized by bacterial proteins that switch on the genes to produce the hemoglobin protein.  Producing mammoth hemoglobin was slightly more complicated because the mammoth DNA was degraded so the hemoglobin genes had to be isolated in pieces.  This meant they couldn’t insert the genes directly into the plasmid, so instead they recreated the mammoth sequence by modifying the elephant construct at the sites where it differs from mammoths.

Once they had the expressed hemoglobin, they then compared the oxygen-binding properties of the elephant and mammoth proteins using standard physiological tests and chemical modelling.  The changes in the amino acid sequence of the mammoth hemoglobin protein, when compared with elephants, appear to be important for cold tolerance, as they allow the mammoth blood to deliver oxygen to cells even at very low temperatures.

“This is true paleobiology, as we can study and measure how these animals functioned as if they were alive today” says Professor Alan Cooper, Director of the Australian Centre for Ancient DNA (ACAD) at the University of Adelaide, where the mammoth hemoglobin sequences were determined.  You can hear more about this research from Alan Cooper on Radio New Zealand here.

Reference:  Campbell KL, Roberts JEE, Watson LN, et al. Substitutions in woolly mammoth hemoglobin confer biochemical properties adaptive for cold tolerance. Nature Genetics doi:10.1038/ng.574

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Tasmanian devil facial tumour disease: too good a match for the immune system Hilary Miller Apr 13

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ResearchBlogging.org
A central premise in conservation genetics is that high genetic diversity is good for a species’ continued survival, and low genetic diversity is bad. This seems intuitively obvious (after all, we all know that you shouldn’t marry your cousin) but actually finding examples in nature where we can say for sure that low genetic diversity has contributed to a population’s demise is difficult.   

However, the recent decline of tasmanian devil populations due to disease provides an excellent example of the perils of low genetic diversity.  Wild devil populations in eastern Tasmania have been decimated in recent years by devil facial tumour disease (DFTD).  This nasty disease is a transmissible cancer spread by biting, and causes large tumours to form around the mouth, interferring with feeding and eventually causing death.  Kathy Belov’s group at the University of Sydney has been studying the genetic basis of DFTD susceptibility in devils and has found that a lack of variation in immune system genes is responsible for the spread of the cancer in some populations.    

Tasmanian devil with facial tumour disease (photo: Menna Jones)

Belov’s group has been studying the genes of the Major Histocompatibility Complex, or MHC.  MHC molecules are a crucial part of the immune system in vertebrates, as they are responsible for recognising foreign invaders and mounting an immune response.  MHC molecules are also an important part of the process of self/non-self recognition that prevents the immune system attacking the body’s own cells.  MHC genes are normally highly variable in populations, with a large number of different alleles (or variants) for each gene.  This variability allows for a wide array of foreign pathogens to be resisted and accounts for differences in disease resistance among individuals.  Thus, populations with low or no variation at MHC genes are potentially susceptible to disease epidemics, as all individuals in the population will be equally susceptible to novel diseases.   

Devil populations in eastern Tasmania have low levels of genetic diversity due to reductions in population size over the last 150 years.  DFTD is so virulent in these populations because the tumours have the same MHC type as healthy devil cells.  Being an infectious cancer, transmission of DFTD between individuals is a bit like a skin graft or organ transplant. If the tissue’s MHC type matches, the transplant is accepted, if not it is rejected.  Because the MHC types of the tumour and the devil match, DFTD cells are not recognised as foreign so no immune response is mounted.  And because of the low genetic diversity, all devils in the population have similar MHC types meaning the disease can easily spread from one individual to another. 

DFTD has spread rapidly throughout eastern Tasmanian populations, causing a 90% decline in total devil numbers.  However, a population at West Pencil Pine in northwestern Tasmania has much lower prevalence of DFTD, suggesting this population harbours animals that are resistant to the disease.  New research by Belov’s lab published in Proceedings of the Royal Society of London last month shows that these populations have differences in their MHC makeup that appear to allow them to resist the disease. 

Here the story gets a little (more) complicated: Tasmanian devils have multiple MHC genes (up to 7 genes each), which fall into two groups on the basis of their DNA sequence.  The tumour cells have both group 1 and group 2 variants, as do the individuals from the susceptible eastern populations.  However the northwestern populations harbour a greater diversity of MHC types, and many individuals from these populations have MHC types which have only either group 1 or group 2 sequences.  None of these individuals have succumbed to DFTD, suggesting they are resistant to the disease.  Belov’s group proposes that in individuals with only group 1 sequences, the immune system will recognise the group 2 sequences on the tumour as foreign and resist it (and vice versa for individuals with only group 2 sequences).   This has yet to be tested in practice, as it is obviously difficult to get permission to infect an endangered species with a deadly disease.  However, these findings are promising for the continued survival of the species and may have a significant impact on their conservation management.

Siddle HV, Kreiss A, Eldridge MD, Noonan E, Clarke CJ, Pyecroft S, Woods GM, & Belov K (2007). Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proceedings of the National Academy of Sciences of the United States of America, 104 (41), 16221-6 PMID: 17911263

Siddle, H., Marzec, J., Cheng, Y., Jones, M., & Belov, K. (2010). MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer Proceedings of the Royal Society B: Biological Sciences DOI: 10.1098/rspb.2009.2362

Feb round-up Hilary Miller Feb 26

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Well this month has been a pretty unproductive one for blogging, but extremely productive in other ways as I welcomed my new daughter into the world on Feb 2nd.  In amongst the endless feeding, dirty nappies and general sleep-deprived haze, I have occasionally managed to get online and thought I’d share a couple of evolution-y things that have landed in my inbox:

The European Society for Evolutionary Biology has launched a new website aimed at improving public education and understanding of evolution.  The site is called Evolution Matters: A Guide to the Creationism/Evolution Controversy, and can be found at http://www.oeaw.ac.at/klivv/evolution/.  The site has lots of useful material, with an outline of the central issues in the creation/evolution debate (also available for download as a pdf), lots of useful links and teaching resources.

The Allan Wilson Centre has launched a new resource on its website, where you can recreate a couple of Allan Wilson’s most well-known research projects – phylogenetic analysis of the Quagga, and analysis of human origins (the project that led to the “Mitochondrial Eve” hypothesis).  Aimed a members of public, the site guides users through the analysis, using real datasets and modern software with the aim of improving understanding of the scientific process.

And if you’re feeling hungry, some geeky science cookies for you: http://www.thekitchn.com/thekitchn/roundup-food-blogs/phd-in-delicious-the-science-cookie-project-not-so-humble-pie-108963

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