Canine Transmissible Tumors: Seeking Immortality By Becoming a Parasite

Cancers are cells that have forgotten who they are supposed to be.  They become independent brats in the body, hogging resources and dividing uncontrollably.  The problem, from the cancers perspective of course, is that being a spoiled brat may bring short-term rewards, like lots of progeny and freedom from having to behave like the cell it was supposed to be, but in the long-term they kill their host from which they have rebelled and thus cause themselves to go extinct.

But, what if a cancer cell could truly achieve the immortality that it really yearns for?  How would it do so and what would happen if it did?  These aren’t just theoretical questions because we have three known examples in nature of cancers that have broken free of their hosts bodies and escaped to live another day. In fact they more than live another day but have gone on to infect hundreds of thousands of other hosts jumping from one to another in their continuing quest for immortality.

One of these cancers, if that is what we can still call them, I have written about before. It is a transmissible cancer that infects Tasmanian Devils (see: What is a Species: Tasmanian Devil Transmissible Tumors). The second is a tumor of domesticated dogs recognized since the late 1800s and was definitively shown in 2006 to be a cancer of a single origin rather than unique occurrences of cancer in each victim.

The tumor is called canine transmissible venereal tumor (CTVT) and is passed from dog to dog through sexual contact.  The cancer is thought to have originated as a unique mutation in a dog long ago and then passed from that dog to millions of domesticated and feral dogs since its origin.  Now, two tumors from dogs from different continents (Australia and South America) have had their complete genomes sequenced (An 11,000 year old dog tumorallowing comparisons of their DNA sequences with dog breeds and each other.  These sequence have allowed scientists to determine the characteristics of the original dog population from which the cancer originated and to estimate how long ago that cancer formed and spread to other dogs.

I want to share some of their findings with you but I also want to ask the question: is this tumor really a dog or should it be considered a new organism?  In addition, I will discuss this tumor in the context of young earth creationist’s views of the origins of biological diversity.

A tale of two tumor genomes

Two CTVTs (dog tumors) were sequenced. One was from an old lineage of domestic dogs from Australia while the other was from a more modern breed of dog from South America.  These two tumor genomes  shared 1.9 million single nucleotide differences with all other dog genomes sequenced so far.   In addition each tumor had just over 100,000 unique mutations themselves or about 200,000 total differences between them.  What this tells us is that from the origin of the tumor in some ancient dog to the time when the common ancestor of these two tumors existed there were around 1.9 million mutations.  Since then more than 200,000 more mutation have occurred with just over 100,000 occurring in each line of cells leading to the tumors alive in these two dogs at the time they were collected.

That sounds like a lot of mutations but how does that compare to mutations in human tumors.  Human cancers are known to have extraordinary high mutation rates such that human cancer tissue that has been grown in the lab will show between 1000 and 5000 mutations compared to the cells of the person from which the cancer was derived.  As a bit of an aside, some recent work (see references) in which parents and their kids had their genomes sequenced it was found that there were fewer than 100 new mutations in the kids compared to their parents DNA.  So the cancer mutation rate is far greater than in normal tissues which have excellent checking and repair systems when they copy their DNA.  Even so these dog tumor have several hundred times as many mutations as any other known cancer.  It would take many thousands of years for any human tumor to come close to having the number of mutations that these dog tumors exhibit compared to normal dog DNA.  This is why it is believed that these tumor cells that infect dogs today are actually an ancient long-lived cancer cell line.

But these are just the mutations that cause one base to be replaced with another.  In addition to these mutations the two tumors shared more than 2100 structural variants compared to dogs and wolves.  These structural variants would be missing or additional pieces of DNA in the genome or places where the genome has been rearranged.  These variants would represent all the changes that occurred since the origin of the cancer to the time when the two tumors had a common ancestor.  Since diverging from their common ancestor these two tumors have each accumulate another 200 structural variants that are unique to each tumor.

Chromosomes from domestic dog (left) and the two tumor cells lines from Australia and South America. The colors show equivalent portions of the genome.  Mixtures of colors on the cancere chromosomes indicate that the chromosomes have been scrabbled up with pieces of DNA from one being moved to other chromosomes.  This is part of a figure from Merchinson et al. in Science which discusses the genome results.  See references for details.

Chromosomes from domestic dog (left) and the two tumor cells lines from Australia and South America (middle and right). The colors show equivalent portions of the genome. Mixtures of colors on the cancer chromosomes indicate that the chromosomes have been scrabbled up with pieces of DNA from one being moved to other chromosomes. This is part of a figure from Murchison et al. in Science which discusses the genome results. See references for details.

What effect has this had on the genome of this cancer?  Well 646 gens of the 22,000 genes found in a dog genome are either defective (don’t work) or have been completely lost (their code has been removed) from the genome.  In some cases genes have been copied or have been moved to new locations in the genome.  646 genes seems like a lot but remember that a tumor cell isn’t ever going to make a fully functional dog and so there will be many genes that will not be needed anymore and so any mutation that occurs in those genes will not be selectively removed but remain in the genome.  Over time those mutations will build up and knock out the function of the genes that were not being used anyway.   At the same time that many genes will be lost through disuse in the cells, there are many genes that have undergone changes that probably make them better able to survive this new lifestyle as a parasite.  The cancers have to be able to get around the host immune system and make themselves easily accessible and transferable in order to continue their existence.  This has certainly required modifications to the genome to give it new properties that the original dog genome did not have.

In addition to genes that are absent or defective the genomes reveals that there are over 10,000 genes, almost half of the entire set of genes!, that had at least 1 mutation that changed an amino acid and thus changed the structure of the protein product of the gene and so potentially could change its function or efficiency.  This is an enormous amount of change in proteins.

When did this tumor come into existence?

The authors of this paper provide an estimate of the ages of these tumors.  They use errors rates from known tumors to get a rough estimate of how long it would have taken for these tumors to accumulate the mutations found in them. They estimate that the common ancestor (ie. the last time that the cells were in the same animals and thus had identical genomes) of this tumor  from a dog from Australia and one from South America was around 500 years ago.  Since that time pieces of that tumor have spread from dog to dog accumulating changes along the way until they came to be in the present day dogs they were collected from.   This seemed like a reasonable estimate to the authors of the paper as this would have placed the ancestor of the today’s tumors around 500 years ago which corresponds to when people began really moving around the world a lot more along with their dogs.

But what about the ultimate origin of the tumor?  This would have happened much earlier than 500 years ago.  Remember that the two sequenced tumors have accumulated bout 100,000 mutations since they diverged from one another but before that this cancer had accumulated 1.9 MILLION mutations since it first became a cancer cell in some unfortunate ancient dog.  The authors estimate that this ultimate origin of the cancer probably occurred between 10,500 to 12,500 years ago depending on the mutation rates used in their calculations.  In addition, the genome sequence enabled them to definitively place the tumors origin in an ancient domesticated dog and not from a wolf or coyote.

A cartoon of the history of dogs, wolves and coyotes showing that the tumor arose in one line of dogs and then has been passed along to other dogs. The two present day dogs represent the two that were sequenced.  Wolves and coyotes apparently are not effected by the tumor.

A cartoon of the history of dogs, wolves and coyotes showing that the tumor arose in one line of dogs and then has been passed along to other dogs. The two present day dogs represent the two that were sequenced. Wolves and coyotes apparently are not effected by the tumor.

So what is it!?

What has happened here?  I don’t think it would too radical to say that this transmissible tumor has evolved into a parasitic organism.  Is this a new species or new life form? It is all a matter of definition? Are parasitic worms living things? Many nematodes and other parasitic organisms have lost the ability to live independently and must use a host to survive and reproduce.  Here we have a lineage of cells that started as a single mutant cell in a single dog. That cell has propagated itself for some 11,000 years and infected millions of new hosts.   That cell/organism has learned how to get from host to host despite now being genetically distinct from its host.  Clearly the tumor is no longer a dog and yet it retains genes and DNA that is most similar to a dog.

A new species? A new life form? A new class of organism? I would say the tumor is not a member of the dog species (Canis lupus var. familiaris).  It probably deserves its own species name and a self-sustaining replicating lineage of cells though I don’t know how it could be classified into a group.  Although it is multicellular in most instances it is really an asexually reproducing cell line like a bacteria.

Ancient dog tumor in the context of young earth creationism

You won’t be surprised to hear that I think this is yet another example of how modern genetic analysis presents serious obstacles to young earth creationist’s views of biological diversity.  How so?  Quite simply most young earth creationist’s of the Ken Ham variety think that only a pair of animals are representatives of a “kind” or “baramin” where saved on Noah’s Ark only 4500 years ago.  In this case, Ham and associates have been telling us that there were no foxes, wolves or coyotes or domestic dogs on the Ark but rather some ancestor of all of these.  Then after these ancestors departed the ark and spread across the earth they adapted to the new environments and “evolved” into all the species we have today.

History of canines infographic based on fossils and DNA sequences.   I found this image here: http://www.wolf2woof.com/index.htm but it is unclear if this is the real source. If you know where this graphic came from please let me know so I can give proper attribution.  Click for a readable size.

History of canines infographic based on fossils and DNA sequences. I found this image here: http://www.wolf2woof.com/index.htm but it is unclear if this is the real source. If you know where this graphic came from please let me know so I can give proper attribution. Click for a readable size.  Creationists propose that all the present day canines “evolved” from at least a dire wolf ancestor on Noah’s ark or possibly eve one of the other fossil lineages shown here.

How does this tumor fit into this picture?  Well, the genetic evidence strongly suggests that the tumor evolved from an ancient domestic dog rather than a wolf.  So wolves, coyotes and domestic dogs must have already evolved into their respective species before this tumor came into existence.   So creationists really can’t put this tumor on Noah’s Ark or its DNA would look as similar to a fox, wolf, coyote as it would a domestic dog. But having originated after the origin of domestic dogs had already diverged from their ancestral wolves and into many different breeds, then all 1.9 million mutations and 2100 other structural rearrangement had to have occurred to these cells between their origin and 500 years ago.  At best, creationists must compress all that change into a maximum of 4000 years if not much less.  These are astronomically high rates of mutation and no model of genetics can be used to support such rates of change.

References:

Conrad, D.F., Keebler, J.E., DePristo, M.A., Lindsay, S.J., Zhang, Y., Casals, F., Idaghdour, Y., Hartl, C.L., Torroja, C., Garimella, K.V., Zilversmit, M., Cartwright, R., Rouleau, G.A., Daly, M., Stone, E.A., Hurles, M.E., Awadalla, P.; 1000 Genomes Project. (2011) Variation in genome-wide mutation rates within and between human families. Nat. Genet. 43:712-714. [doi: 10.1038/ng.862]

Transmissable Dog Cancer Genome Reveals the Origin and History of an Ancient Cell Lineage.  Elizabeth P. Murchison, David C. Wedge, Ludmil B. Alexandrov, Beiyuan Fu, Inigo Martincorena, Zemin Ning, Jose M. C. Tubio, Emma I. Werner, Jan Allen, Andrigo Barboza De Nardi, Edward M. Donelan, Gabriele Marino, Ariberto Fassati, Peter J. Campbell, Fengtang Yang, Austin Burt, Robin A. Weiss, Michael R. Stratton.  Science 24 January 2014:   vol. 343 no. 6169 pp. 437-440 DOI: 10.1126/science.1247167

Comments

  1. I want to share some of their findings with you but I also want to ask the question: is this tumor really a dog or should it be considered a new organism?

    I hadn’t even thought of that! I suspect that some would say that it is mere ‘devolution’ – dog-to-microbes, not microbes-to-man – but regardless it presents a significant obstical to the notion of immutable kinds.

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    • yeah, I’m sure that the loss of genes and rearrangements would be looked at as a degeneration but there has also been positive selection for genes that have enabled this cancer to avoid the immune system. It has learned interdependency. I have a colleague who tells me that there is some indication that this thing can even jump to wolves and foxes in which case it may jump species. If that is the case then it really is a parasitic life form regardless of its origins.

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