Author Archives: Floyd A. Reed

Lamarck and Giraffes!: Closing the Circle

You're going to think I'm nuts but this is too good to pass up!

lamarck_giraffe2

One pre-Darwinian theory of evolution is credited to Jean-Baptiste Pierre Antoine de Monet, Chevalier de Lamarck (1744 – 1829). One component of his theory was "L'influence des circonstances" (the influence of circumstances) which we take today as an acquired trait (not a genetic trait), like bigger muscles, etc., that is a response to an environmental factor and is transmitted from parents to offspring. This (the transmission of environmentally influenced acquired traits) is referred to as Lamarckism or Lamarckian evolution.

A common example used in textbooks to illustrate this is the length of giraffe's necks. Giraffe's were originally short necked but each generation the adult giraffes would stretch their necks to reach higher leaves that were left behind. Stretching their necks resulted in the adult's neck being slightly longer (than if it had not stretched). Importantly, according to the theory, this trait, longer necks, was transmitted to the giraffe's offspring. Over many generations the necks grew increasingly longer. In Lamarck's view interaction with the environment (circumstance) led to an inherited physical change in the organism.

Okay, so with the modern synthesis of evolution incorporating Darwinian adaptation and Mendelian inheritance, among other things, we can comfortably laugh at this scenario.* However, in recent decades the role of epigenetic inheritance has been increasingly understood. With epigenetics there are not changes to a DNA sequence (mutations as we generally understand them) but "tags" are added to the DNA sequence that alters the expression of a gene. Importantly, factors in the environment the organism is exposed to change how these tags are added and this can be inherited across generations. So, there is a way for an organism's environment to influence inherited physical changes in an organism's future descendants.

A famous example is "agouti" coat color in mice. Mice that are heterozygous for an A[vy] allele have variable phenotypes ranging from yellow to brown, as a result of the influence of environmental effects.

bpa

Interestingly, when parents are exposed to compounds like Bisphenol-A (BPA) this can cause a trans-generational shift towards more yellow descendants. On the other hand when the parents diets are supplemented with large amounts of folic acid, vitamin B12, or zinc there is a trans-generational shift towards more brown ("pseudo-agouti") descendants. This has been determined to be because of differences in methylation (one form of the DNA "tags") of a promoter region of the Agouti gene sequence.

agoutimethcpg2

There are many more examples of epigenetic effects for a range of traits in a range of species. I am not going to attempt to review them here, but this is an active and interesting area of research and we are just beginning to understand how extensive this might be and the role it might play in, for example, human genetics (think for a moment of all the vitamins and chemicals you are exposed to and what effects this might have on your children and grand-children...).

Wiki_Bisulfite_sequencing_Figure_1_small

How do you detect epigenetic tags on a DNA sequence? One method is to treat the DNA with bisulfite first before amplifying and sequencing it. Bisulfite converts cytosine to what ends up appearing as a thymine (a C (to a U) to a T in the DNA sequence) but it does not affect cytosines with a methyl group that is attached. (To be clear there are more types of epigenetic "tags" then methylated cytosine, and not all types of epigenetics modify DNA nucleotides; this is just one type.)  So, you can compare bisulfite treated and non-treated DNA sequences and work out if there is a difference in epigenetic modifications.

Okapi2

Okay, bear with me. Recently the giraffe genome was reported in a comparative genomics project that included its shorter necked cousin the okapi (http://www.nature.com/ncomms/2016/160517/ncomms11519/full/ncomms11519.html). A number of genes with changes that likely lead to the giraffe's unique development were identified including FGF growth factors and HOX genes that guide development. Furthermore, the authors found changes in genes that are likely involved in tolerating toxins in their diet (acacia leaves for example are very toxic and contain a range of alkaloids).

Okay, you can guess where I'm going with this.  Giraffes eat food that is very biologically active and toxic to many other species...  Just for fun, are there epigenetic signals in the genes implicated to be responsible for a giraffe's long neck? Do these vary among giraffes? Are they correlated with neck size and/or diet? Does the signal transmit across generations?   (Could epigenetic potential have evolved to be sensitive to, and respond to, trees of different heights in the giraffe's (ancestor's) diet?)  It would be fairly straightforward to work the first part of this out using giraffe DNA samples and bisulfite sequencing. Giraffe's already serve as excellent examples of the process of evolution (perhaps most famously the route of the recurrent laryngeal nerve in giraffes). We now have the tools to determine if, after all of these years (centuries), there could also in fact be a Lamarckian "L'influence des circonstances" in giraffe neck length?


  • However, to say that Lamarck was at a conceptual dead end and only known for the theory of inheritance of acquired characteristics is a part of the general misunderstanding that is associated with the man. He was a French naturalist that was involved in a wide range of scientific topics. Lamarck rebelled against the predominant thought of uniformitarianism in nature at the time. His idea around 1800 that some aspects of nature were mutable and could change was revolutionary and formed part of the foundation for Darwin's theory of natural selection and other components of the theory of evolution.

Further reading

Agaba, M., Ishengoma, E., Miller, W. C., McGrath, B. C., Hudson, C. N., Reina, O. C. B., ... & Praul, C. A. (2016). Giraffe genome sequence reveals clues to its unique morphology and physiology. Nature Communications, 7.
Feil, R., & Fraga, M. F. (2012). Epigenetics and the environment: emerging patterns and implications. Nature Reviews Genetics, 13(2), 97-109.
Gillispie, C. C. (1958). Lamarck and Darwin in the History of Science. American Scientist, 46(4), 388-409.

Is Natural History Disappearing from Academia?

A new study came out about attitudes towards natural history and the coursework available.

Barrows, Cameron W., Michelle L. Murphy-Mariscal, and Rebecca R. Hernandez. "At a Crossroads: The Nature of Natural History in the Twenty-First Century." BioScience (2016): biw043.

I am copying excerpts from the abstract here:

"The relevance of natural history is challenged and marginalized today more than ever. ... Early-career scientists surveyed agreed that natural history is relevant to science (93%), and approximately 70% believed it “essential” for conducting field-based research; however, 54% felt inadequately trained to teach a natural-history course and would benefit from additional training in natural history (more than 80%). ... Our results indicate a disconnection between the value and relevance of natural history in twenty-first-century ecological science and opportunities for gaining those skills and knowledge through education and training. "

Here is a link to the original article and a discussion about it at the Scientific American blog:

http://bioscience.oxfordjournals.org/content/early/2016/04/08/biosci.biw043.abstract

http://blogs.scientificamerican.com/artful-amoeba/80-of-young-environmental-scientists-could-use-more-natural-history-training/

Red pigment in birds: a role in speciation?

There are various hypotheses about the role of behavior and speciation. One of these is the evolution of mate choice, where a genetic variant results in a phenotype that potential mates respond to, and the response is also under genetic control. This requires the simultaneous evolution of at least two loci (the signal and the behavioral response) and a problem with this line of reasoning is that the alleles at the two genes can quickly recombine away from each other unless they are genetically close together along a chromosome (and/or recombination is suppressed by a chromosomal rearrangement). Another theory is the "good genes" hypothesis. That an individual with advantageous alleles can also signal this phenotypically and mates will choose these individuals (a cool example of this is meiotic drive suppression in stalk eyed flies).

This is interesting. Two studies just came out, one in the zebra finch (http://www.cell.com/current-biology/fulltext/S0960-9822%2816%2930400-6) and another study in the canary (http://www.cell.com/current-biology/fulltext/S0960-9822%2816%2930401-8), and found that the gene responsible for variation in red pigment in the beak and feathers is due to expression levels of CYP2J19. Interestingly, this pigment is also used in the retinas to screen certain colors of light. And, it is expressed in the liver. Many of the CYP family (a.k.a. the Cytochrome P450 family) of genes are involved in detoxification of a range of compounds.

This is purely speculative, I have not had time to investigate what is known about CYP2J19's precise functions, but what if CYP2J19 in birds acted simultaneously as a mate choice signal (beaks and feather pigment) and a component in the behavioral response (retina pigment) and maybe also had a "good genes" role as well (liver detoxification)?  (See also the "green-beard effect" which CYP2J19 variation may also be a candidate for.)

Regardless, this should be followed up in other groups of birds. There are rapid speciation events associated with transitions between red and yellow plumage and a comparative study of DNA variation at CYP2J19 in groups like the Hawaiian honeycreepers might be enlightening.

High-res image. Image: Douglas Pratt, in Conservation Biology of Hawaiian Forest Birds, Yale University Press" Donna.Anstey@Yale.edu (Tiff version available, doug.pratt@ncdenr.gov)

Genohub: kayak for next generation sequencing

Part of the issue with next generation genome-level sequencing projects in a lab is finding the sequencing service provider. The prices can vary by quite a bit and a lot of word of mouth and point-to-point communication goes around, which can take some time.

I just learned about genohub where you can fill out a form for your sequencing project (here is just a random example).

genohub

Then click find and it returns information about different sequencing centers (these are just examples, not endorsements).

genohubresult

That combination is expensive.  Here is the result of another search for 20X sequencing of a genome 450 Mbp in size.

genohubdnagenomeseq

The cheapest ones are all single reads, but you can scroll down for paired end sequencing for genomes with a lot of repetitive elements.

genohubdnagenomeseqpaired

National Academies of Sciences Report on Genetically Engineered Crops

This was just released yesterday from a committee chaired by Fred Gould:

http://nas-sites.org/ge-crops/2016/04/27/report-release/

"This consensus report examines a range of questions and opinions about the economic, agronomic, health, safety, or other effects of genetically engineered (GE) crops and food. Claims and research that extol both the benefits and risks of GE crops have created a confusing landscape for the public and for policy makers. This report is intended to provide an independent, objective examination of what has been learned since the introduction of GE crops, based on current evidence."

CRISPR's

I think there are only two, maybe three, people left in the world that have not heard about the CRISPR-Cas9 system. It originates from a type of bacterial immune response but has been recruited as a genetic tool and has swept through the genetic engineering community in the last few years. In fact, one of the criticisms of our last NIH grant applications was that we were not using CRISPR's...  Here are some links to a few articles of wide interest regarding this technology.

DARPA, Gene Drive Technologies, and the ENMOD Treaty

I just returned from a "gene drive" workshop at NCSU's Genetic Engineering and Society Center. There is a lot to talk about from the meeting. Here I want to focus on a couple of specific details that came up in reference to the military funding of genetic technology. The meeting was held under Chatham House Rule, so I cannot identify the people who made the original statements. Some of these were in group discussions and some of these were personal one-on-one conversations. As a brief, overly terse, background statement to describe a complex field: gene drive technology is a new emerging technology that is potentially very powerful and could be used for beneficial humanitarian and species conservation applications where other methods have fallen short in their long term effectiveness.

First of all, I was told that DARPA is interested in funding gene drive technology for environmental modifications. DARPA helps to develop new technologies for military applications.  This could be for both species conservation applications as well as preventing infectious disease (and also there is obviously the possibility of malicious hostile use in military applications but this was not brought up). Apparently a man named Dr. Jack Newman (link) is slated to become the program manager of mosquito gene drive technology at DARPA.

So---to be frank---I believe this is potentially a very bad idea for many reasons. The first is strategic. If these kinds of technologies are to ultimately be used for beneficial reasons they must be acceptable in some degree to the public so that they can become adopted and utilized. The Pacific Islands have a very negative track record of being used for testing grounds of new technologies. This ranges from classical bio-control releases of invasive species, to loss of traditional land to military activities, to, probably the most glaring example, nuclear testing in the Marshall Islands that displaced Native People and resulted in a region becoming uninhabitable from the resulting radiation (also note French nuclear testing, under protest, in Tureia, link). There is nested within the issues of the loss of self determination resulting from colonialism by many Western Countries across the Pacific. Like it or not, public perception is a very real force that cannot be ignored. The Three Mile Island accident in 1979 led to an effective moratorium on new nuclear reactor construction until 2012; however, many of these new projects have also been canceled with the more recent Fukushima disaster also playing a role. The public reaction to GM Crops has also had a very real effect on the laws surrounding the technology and adoption of the technology around the world including in the Pacific (e.g., the GM Taro and GM Papaya controversies in Hawai'i, link).* Right or wrong, in the Pacific, military funding of a new technology will be initially evaluated within the perspective of other military tests of new technologies and the effects this has had on the people of the Pacific Islands. Even more relevant to gene drive technologies, in the 1970's a World Health Organization project to test the release of sterile mosquitoes in India (to suppress the local population and limit the transmission of disease to humans) was shut down due to public perceptions that it might also be a secret military bio-warfare test (link, incidentally there are also some documents on WikiLeaks related to this).

In a broader ethical-moral sense (and this is very much a personal opinion from the perspective of a US citizen) are we comfortable with the military guiding and controlling the research that goes on in our country? This may sound like hyperbole; however, a comparison of the huge difference in the levels of US military funding (on the order of $610 billion) and National Science Foundation funding (on the order of $7 billion) is objectively dramatic. Advances in research depend on grant funding and support. Which technologies government funding agencies choose to support affects not only the advancement of these technologies but the direction they develop in and as a direct result the future applications of these technologies (the history of Project Orion is one example where limited funding sources and issues of potential military uses caused development focused on military applications yet ultimately stopped a line of scientifically promising yet controversial research, link).

Ideally, for gene drives technologies to be able to realize their potential in beneficial applications, they should be supported and developed by sources other than the military and private companies---and yes, this is strongly motivated by public perception as well as ethical principles. Scientific funding bodies as well as state and local funding have more of a long term potential benefit than is initially apparent. Furthermore, accepting funding from the military lends false support to continuing the objectively inflated funding of the military at the expense of government agencies devoted to scientific research (NSF and others); at the end of the day the military can say that it should continue to receive research funding because of the projects it has supported, but this comes with a social cost. Wouldn't it be better if NSF could make this statement instead without the social cost?

Okay, now comes the ace card that I have been hiding so far in this article... At the meeting, someone brought up (within the context of more "traditional" synthetic biology) that the US is a signatory to the ENMOD international treaty which came into force October 5, 1978. This treaty prohibits the military from using environmental modification technologies that have widespread and/or long-lasting effects. Interestingly, "Environmental Modification Technique includes any technique for changing – through the deliberate manipulation of natural processes – the dynamics, composition or structure of the earth, including its biota" (full text). This gets into philosophical discussions about the role of physical coercion by the military and the state, which I do not want to go into here (links for reference, military, monopoly on violence); however, I will appeal to the common-sense notion that military force by a state is a hostile act although this is more difficult to realize when it is done in a way that aligns with your own interests.  Since gene drive technologies are deliberate manipulations of natural biological processes with long term and possible widespread effects on manipulation of the environment, is DARPA military funding of gene drive technology even legal according to international treaty that the US agreed to support?

* I don't mean to sound overly pessimistic; there does seem to be a disconnect between the public-perception-of-public-perception and public-perception. When I talk to people about the type of work I am doing in the lab and the possibility of future applications at times I have been laughed at and told it will never be possible because people in Hawai'i are dead set against any genetic modifications. However, when I go into more detail about the non-native mosquitoes being modified to help protect native bird species and the self limiting nature of the genetic technology many of these same people are personally positive about the applications, but maintain that most people would be against it. Often the debate seems to be framed in terms of science versus people, especially native interests, with the recent debate over the telescope at Munakea as an example (link), and it becomes all to easy to fall into overly polarized positions. GM Papaya and GM Taro (Kalo) are perhaps good examples of different ends of what is acceptable with genetic modification technology. GM Papaya is not without controversy but is now widely adopted and commercially important in Hawai'i; however, GM Taro was rejected in large part due to the importance of Kalo to traditional Hawaiian culture and its role in Hawaiian mythology. As a diverse collection of cultures and values that does not always agree as individuals we can still have a public dialogue and make common choices; everyone has a role to play.