Debunking myths on genetics and DNA

Friday, June 29, 2012

Dual-use research of concern

I'm still reading (and very much enjoying) last Friday's Science issue on the flu pandemic. In [1], Anthony Fauci and Francis Collins summarize very well why the flu presents a potential threat:
"Influenza viruses have animal reservoirs, especially in birds and pigs. They can undergo extensive genetic changes and even jump species, sometimes resulting in a virus to which humans may be highly vulnerable."
Over the last hundred years, this happened four times: in 1918 (the Spanish flu), in 1957 (the Asian flu), in 1968 (Hong Kong flu), and, the last time, in 2009 with the H1N1 pandemic (swine flu). H5N1 has not initiated a pandemic because it is rarely passed between humans and it infects only through direct contact with infected birds. So far there have been about 600 total cases, of which nearly 60% have resulted in deaths (though this last number is likely to be inflated as often not all non-fatal cases are reported to hospitals). Given these statistics, if the virus were to spread more easily (for example through sneezing or coughing), this would entirely change the threat level, hence the concern when two labs independently announced that they had found an H5N1 mutant able to spread through aerosol in ferrets.
"One of the goals of pandemic influenza research is to recognize and anticipate how viruses are evolving in the wild toward a phenotype that is dangerous to humans, thereby staying one step ahead of potential pandemics."
That's why studies like the ones conducted on ferrets are so important. Yes, the virus was genetically engineered in a lab, but once you have it, you can address the following questions: how likely are those mutations to appear spontaneously? Can we use the virus to produce a vaccine? Are the current antiviral drugs successful in containing the infection or is there a need to develop new drugs?
"However, whenever one deliberately manipulates a virus or a microbe, it is always possible, at least theoretically, that the research results could be used by bioterrorists to intentionally cause harm, or that an accidental release of a pathogen from a laboratory could inadvertently cause harm."
Any research that presents such dual potential of benefit and risk/threat is referred as DURC, which stands for dual-use research of concern. The controversy around the two H5N1 papers clearly proves that we need better ways to assess and regulate DURC research, as well as mitigating the risks while highlighting the benefits.
"There is still no consensus on how to practically define DURC; whether it is feasible to identify and regulate DURC experiments; how to address risks associated with DURC; and how to balance this risk with the necessity of fostering life sciences research for public health and biodefense [2]."
It is a necessity for scientists to be open about their research. Research is rarely conducted in isolation. Open discussion is what fuels great ideas. A DURC policy that requires new protocols and manuscript redactions threatens this openness. Furthermore, it isn't feasible to retroactively restrict scientific information since most scientists are required to write reports describing their current research, as well as give talks and presentations at official meetings. When the NSABB made its recommendation not to publish the two H5N1 studies last year, it was probably already too late. Many people in the scientific community had already heard sufficient details, even prior to their publication.

What are your thoughts on the matter?

[1] Anthony S. Fauci,, & Francis S. Collins (2012). Benefits and Risks of Influenza Research: Lessons Learned
Science, 336 (6088), 1522-1523

[2] Carrie D. Wolinetz (2012). Implementing the New U.S. Dual-Use Policy
Science, 336 (6088), 1525-1527

Wednesday, June 27, 2012

Recycle Runway: the art of turning garbage into beautiful garments

If you've been through the Atlanta airport lately, chances are, you noticed the dress in the picture above. Well, I did. And I had to stop and look. And since I had a tight connection, I couldn't stop for too long, so I wrote down the words "Recycle Runway," and Googled them the next day. And that's how I met Nancy Judd and her incredible work.

Nancy is an artist and a fashion designer like no other. Why? Because all of her garments are made from recycled materials: cereal boxes, aluminum cans, paper, and even rusty nails. Her work is part of the Smithsonian permanent collection and, besides the Atlanta airport, it has been on display at the airports of Pittsburgh, Albuquerque, and Phoenix. Her mission? By turning rejected things into elegant fashion, Nancy educates the public about sustainable living. I was so awed by her work and mission that I knew I had to have Nancy come over to CHIMERAS and tell us her story. And I was thrilled when she agreed!

It's such an honor to be talking with you, Nancy. How did you get started designing fashions from recyclables?

I made my first recycled fashion in 1998-- while working as the recycling coordinator for the City of Santa Fe, I realized that art and fashion could be used to raise the consciousness of the public about recycling in a fun and positive way. I started an event called the Recycle Santa Fe Art Market that is still going strong! The opening night always features a recycled fashion contest and I would make a dress every year to promote the contest. Soon I had a wonderful collection of recycled garments, and I started to get invited by other recycling coordinators around the country to give recycled fashion shows in their communities.

I am intrigued by your "crime scene" dress. Where did you get the idea?

Over a year ago I asked my cousin, Grant, and my friend, Michele, who are both police officers, if they would save “police tape” from crime scenes for me. Within about 6 months I received big tangles of yellow tape, some with stories I did not want hear. It is made from police tape that reads: “Crime Scene Do Not Enter”. At first I thought it would be an edgy and fun garment, but soon I realized that this piece is very serious… for me it’s the most provocative work of art that I have ever created. It is about many forms and levels of violence: It is about sexual abuse. It is about the destructive effects of the fashion industry on the people who grow, sew and model clothing as well as those of us who are made to feel inadequate in numerous ways so as to “feed” the industry with consumers. It is about the destruction we have done to the body of mother earth. It is about the over 200 toxic chemicals deposited in each of our bodies from our poisoning of the earth.

No, this did not end up being a fun dress. But like many of my pieces it is deceptive. From afar people may find it to be an appealing design, and only upon closer inspection will they discover some of the deeper meanings.

Wow. It was intriguing to see the dress at the airport, but it's even more fascinating to hear the story behind it. What inspired you to start using recycled materials to create fashion garments?

From an artistic stand point, the challenge of transforming trash into elegant fashions is very exciting. I love watching people discover that what they thought was a glamorous dress, is made from garbage, and recycling classic styles from the 1900s-1950s works to enhance that juxtaposition.

As an environmental educator I can use the garments to initiate a deeper “conversation” with my audience about environmental stewardship in a creative context.

On a personal level, working with garbage has been an often unconscious way of working through emotional challenges.

How do you pick the materials to use and what was the most unusual material you have used so far?

I choose materials based upon the project. If the piece is sponsored by an organization then I use their materials, which they will often send to me. The Environmental Steward-ess is a recent example of this process. In other cases, I start with a waste product that I want to use and then design a garment that I think is well suited to the properties of that material. The Faux Fur Coat is a good example of that.

As for the most unusual things I've used, definitely car parts! Toyota commissioned me to dig through their recycling containers (note: they recycle betwen80%-95% of their garbage, so there is not much in their trash cans to choose from!). This garment proved to ME that I could make anything elegant… even car parts!

And indeed, it turned out fantastic -- check it out!

Have you considered doing other things (like home decor, utensils, etc) with recycled garbage, or are you pretty much sticking with fashion design?

No, for whatever reason my inspiration comes in the form of the garments, I don’t think I would make anything that interesting in other areas!

I am not interested in creating manufactured sellable items. My focus is using art to raise awareness about environmental issues. I love the challenge of making garbage beautiful, glamorous and sexy. By publicly displaying my recycled garments, I invite people to redefine their definition of waste, garbage and trash. I strive to transform the concept of “waste” into “resource” and encourage individual responsibility for the environment in a fun, playful and positive context.

What is the piece that you loved the most doing and why?

The piece that I am working in any given moment is always my favorite. I always have the most passion for my current project! My next project is a Toyota and Audubon Society fellowship called TogetherGreen. The project will engage at least 200 households—through sixth grade students from low-income under represented families in Santa Fe schools—in reducing energy use. The students will begin by recording baseline energy use in their homes, then they will be given a list of easy and no/low cost energy conservation actions they can implement with their families’ help. Participants will document implementation of these actions for a final report on the amount of energy saved and CO2 reduced. My plan is to incorporate this information into the recycled garment, which will be made of waste items related to energy conservation.

This is all so fascinating. Thank you so much, Nancy, for sharing your story with us today and, most importantly, for the mission you have taken over. I'm a strong believer in the proverb, "We don't inherit the Earth from our fathers, we borrow it from our children." As such, we all need to do our part in keeping our planet clean. I wish you all the best in your work and endeavors.

If you enjoyed reading about Nancy's work as much as I did, go check out her website: you can find out about her current projects, upcoming events, and you can browse the incredible collection of dresses. You'll be amazed at the beauty Nancy creates with the most incredible materials.

Monday, June 25, 2012

Flu pandemics: are we prepared?

The first avian flu controversial paper appeared in Nature last April, and the second one just came out in the last issue of Science. For the occasion, Science also published a series of essays from various experts in the field discussing the issues at stake and what we learned. The most fundamental question is: in case of a flu pandemic, are we prepared?

Rino Rappuoli and Philip Dormitzer discuss what can be done in the event of a flu pandemic, basing their observations on the lessons learned from the 2009 H1N1 (the so called "swine flu") pandemic [1]. In 2009, H1N1 vaccines were successful in reversing the rise of flu cases. However, they became available only after the pandemic had started (8 months after the first case had been reported) and only in wealthy countries.

The authors present four possible preventive approaches.

(1) Pre-pandemic vaccination: in 2009, people exposed by either vaccination or infection to the H1 strain, were able to sustain the H1N1 infection. If a vaccine induces a strong antibody response, those antibodies will work also against distantly related strains, indicating that vaccination against the H5 strain may be able to prevent a possible H5N1 pandemic.
"Because H5N1 infection of humans is so rare, the population has not been primed by previous exposures. This lack of prior exposure makes the population more vulnerable to severe disease caused by highly virulent H5N1 strains and makes immunization more difficult, necessitating the use of adjuvants, higher antigen content, and two doses to elicit sufficient antibody titers."
(2) New cell culture technologies: currently, most vaccines are grown in cell cultures, which is dependable on egg supplies and lengthens the production time. New cell culture technologies would increase the manufacturing capacity of the vaccine, which is needed because mathematical models show that "the proportion of the population that must be immunized for effective immunity is likely to be greater than 80%."

(3) Extended Program on Immunization (EPI): currently only rich countries have broad vaccination policies and not many recommend routine flu immunization. Initiated by the World Health Organization, the EPI program sets goals and a standardized vaccination schedule for all children world-wide. Currently, flu vaccinations are not part of the EPI program, but if they were introduced within the program this would expand the availability of the vaccines beyond the rich countries.

(4) Synthetic seed generation: a viral strain is needed to make a vaccine and cloning these strains takes time. Rappuoli and Dormitzer propose as an alternative synthesizing the genes instead to generate synthetic virus. Novartis, the multinational pharmaceutical both Rappuoli and Dormitzer work for, has an ongoing project to use synthetic genomics that would reduce vaccine production time by up to two months.
"In conclusion, while we wait for the development of a universal influenza vaccine, we have practical options that we could implement today to reduce the risk of mass global mortality from the next influenza pandemic."

[1] Rappuoli1, R, & Dormitzer, P. (2012). Influenza: Options to Improve Pandemic Preparation Science, 336 (6088), 1531-1533 DOI: 10.1126/science.1221466

Thursday, June 21, 2012

Do angels know more in the evening than they do in the morning? Ian Tregillis muses about books, writing, and Medieval theology

Do you remember my friend, colleague, writer, novelist, scientist, and author of the Milkweed trilogy Ian Tregillis? Of course you do! He's one of the first writers I interviewed last year, and let me tell you, Ian is a really interesting person to talk to. So, if you missed the first interview, go read it now, and then come back because today Ian is back to tell us about his next books. That's right, not just the Milkweed sequel, but also his other projects!

Ian, you have a very exciting (and busy) summer ahead of you: Bitter Seeds, the first book in the Milkweed Trilogy, comes out from Orbit in the UK on July 12, The Coldest War, Book II in the Milkweed trilogy, is due on the shelves on July 17, and that's also when your new novel, Something More Than Night, is due on your editor's desk.

Let's start with The Coldest War: Can you give us a sneak peek at what's coming next for Klaus, Marsh, and Gretel? Will we be meeting new characters in this sequel?

There are definitely some new characters in this novel. Because The Coldest War takes place more than 20 years after the end of Bitter Seeds, the leadership of Milkweed has changed hands since the war. By the early 1960s, the people at the helm of Milkweed have a very different philosophy from the wartime days when John Stephenson ran
the show. The enemy and the nature of the conflict have changed considerably.

But the primary characters of The Coldest War are still Marsh, Will, Klaus, and of course Gretel. In the previous novel, we saw Gretel laying down the seeds of a grand plan that only she seems to understand. Now, 20 years later, her plan is coming to fruition. And everybody plays a part, whether they want to or not -- her brother, Klaus; the warlock, Will; and the retired ex-spy, Marsh, most of all.

The passage of time has changed everybody. Some for the better, and some for the worse...

That's so intriguing, I can't wait to read! I should mention for those readers who love audiobooks and can't wait until July, that the audiobook is already out.

I'm so excited about your new novel, Something More Than Night. We both share a great love for Raymond Chandler and, from the few chapters I read of this new work of yours, Chandler relives through your extraordinary prose. Not many people can pull that off, Ian, but you do so in the most beautiful way. Can you tell us how this story was born and maybe give us a little introduction on the characters?

First, thank you very much indeed for the kind and encouraging words about this new project! They mean a lot to me -- "Something More..." is so different from the Milkweed books that I worry how readers will react. I just hope that it finds an audience. (The same hope we have with every book, I suppose!)

The idea for "Something More" actually predates my brainstorming for the Milkweed books. But it took a very long time for all the pieces to crystallize. I knew that I wanted to write a book that took place at least partially in Heaven. I'm fascinated with certain strains of medieval European theology -- back when folks like Thomas Aquinas were contemplating the nature of angels. Do angels know more in the evening than they do in the morning? Do angels pass through the intervening space when they travel from point A to point B? Can several angels occupy the same space? These questions, and others like them, represented the bleeding edge of 13th century philosophy. Fun stuff! And irresistible to a writer...

Even more fascinating to me is the celestial Choir -- the hierarchy of angels. Angels, Archangels, Principalities, Powers, Thrones, Virtues, Dominions, Cherubim, Seraphim... Angels in the form of wheels, angels with six wings, angels covered in eyes, angels with the faces of men and lions and oxen. What a wonderful cast of
characters to populate a novel!

I just had to attempt a mystery in this setting. So around the time I started serious brainstorming for this novel, I picked up some noir detective novels from the 1920s through the 1940s. And I quickly fell in love with that delicious slang -- all the talk of bulls and dames and loogans. Not to mention, of course, that wonderful Chandlerian prose.

I'd been struggling to piece together the overall concept for this novel. But once I decided to combine the celestial Choir with the tropes of noir fiction, the whole project started to click. It came together pretty quickly after that.

So the end result is a Dashiell Hammett and Raymond Chandler-inspired murder mystery set in Heaven. Imagine central casting for a noir novel juxtaposed with Archangels, Cherubim, Seraphim, and all the rest. "Something More" also features appearances by a dirty priest and the Voice of God.

(The title, incidentally, comes from a famous Raymond Chandler quote: "The law was something to be manipulated for profit and power. The streets were dark with something more than night.")

How exciting! Alternate history, and a mystery set in a fantasy world: what's next for you, Ian? Do you see yourself ever getting into a completely different genre?

I enjoy trying different things. For me, the most fun comes from working on projects that force me to stretch myself. I'm a big believer in writing against obstacles. Sometimes I stretch myself too far, but that isn't necessarily bad. In fact, I probably learn more from my failures than my successes! So, whatever I write next will almost certainly be quite a bit different from both the Milkweed books as well as Something More Than Night.

For instance, I love space opera, and would love to try my hand at it. If I ever come up with a decent idea for it, that is. (So far, I haven't.) At the moment, though, I'm kicking around ideas for a science-fictional conspiracy thriller, and a magical secret history. The next book will probably turn into something entirely different from either of those, though. Books have a tendency to mutate, don't they?

Just about all of my ideas have a genre element to them. Or if they don't start out that way, they usually pick one up along the way...

Ooh... "science-fictional conspiracy thriller"... fun! Thanks so much, Ian. I can't wait to read The Coldest War and in the meantime you already have me looking forward to your next projects.

If you enjoyed getting to know Ian, you should check out his website,, where you can find updates on his upcoming books and appearances, excerpts, and follow Ian's blog.

Monday, June 18, 2012

Chromatin and oncogenesis

DNA is packed inside the nucleus of our cells, folded around proteins in a "yarn" called chromatin. In an older post I discussed how chromatin changes affect gene expression. A recent PNAS paper [1] explores the relationship between chromatin conformational changes and cancer. They studied one family of genes in particular, ERG, which is part of the larger family of genes called ETS. In order to understand the paper I had to learn about this ETS family of genes and, let me tell you, it's quite fascinating.

The ETS genes are a family of transcription factors, proteins that bind to particular loci in the DNA and thus control DNA transcription. From the Wikipedia page: "The ETS family is present throughout the body and is involved in a wide variety of functions including the regulation of cellular differentiation, cell cycle control, cell migration, cell proliferation, apoptosis (programmed cell death) and angiogenesis."

ETS stands for "E Twenty-Six," which is actually a leukemia virus. This is because the founder of the family, ETS-1, is the precursor of a retroviral oncogene: yes, another endogenous viral sequence! This particular gene is transduced (transferred) by the E26 virus. Several studies have associated the deregulation of the expression of this gene with tumorigenic processes.

Back to the paper: Rickman et al. investigated oncogene-mediated chromatin structure changes in ERG, a subfamily of ETS that is often rearranged and overexpressed in prostate cancer.
"ERG interacts with several cofactors and other transcription factors including AR to regulate the expression of thousands of genes that favor de-differentiation, cell invasion, and neoplastic transformation of prostate epithelium when overexpressed. We therefore hypothesized that changes in global gene expression induced by ERG overexpression could be associated with global changes in the 3D structure of chromosomes."
"Our data show that overexpression of ERG is associated with broad chromatin topology changes and, interestingly, that ERG binding is significantly associated with hotspots of differential chromatin interactions."
This association still does not prove causality, as the pathway from overexpression to chromatin conformational changes could be more convoluted, but it certainly points to a correlation between these changes in chromatin topology and the expression of genes responsible for prostate cancer. This association is likely to be found in other sets of genes relevant to other types of cancers.

[1] Rickman DS, Soong TD, Moss B, Mosquera JM, Dlabal J, Terry S, Macdonald TY, Tripodi J, Bunting K, Najfeld V, Demichelis F, Melnick AM, Elemento O, & Rubin MA (2012). Oncogene-mediated alterations in chromatin conformation. Proceedings of the National Academy of Sciences of the United States of America, 109 (23), 9083-8 PMID: 22615383

Thursday, June 14, 2012

Cinque Terre

I'm a little behind in preparing my post, so while I stall a few more days I thought you might enjoy a few pics of one of the most beautiful places in Italy. :-)

Monday, June 11, 2012

Do rare variants hold the missing answers?

Most DNA is identical across subjects. However, some genes are polymorphic, which means different alleles of the same gene are present across individuals. Since we all have two copies of each gene, individuals who carry two identical copies are called homozygous, and those who carry different copies are called heterozygous. Typically, one allele is most common in the population, the "wild type," and the other ones, present at lower frequencies, are called "mutants." Single-base differences are called single nucleotide polymorphism, or SNP (pronounced "snip"), and, on average, they occur about every thousand base pairs.

For the past 20 years, genetic research has focused on finding associations between SNPs and major diseases like cancer, Alzheimer, diabetes, etc. Back when I was doing this type of research, from 2004 until 2006, we used to exclude SNPs whose minor allele frequency (MAF) was lower than 0.5% in a given ethnic group. The logic was that it was too rare to make any significant contribution. Back then we were sampling a few hundred people and we simply didn't have enough statistical power to detect an effect when the frequency was that low.

A note from the statistician: SNP association studies ask the question, "Does mutant allele X raise the risk to develop disease Y"? As it happens with all statistical tests, the answer comes with a p-value, and the p-value represents the probability of observing the given data distribution by chance. P-values of 0.05 or lower are "good" because they mean that the chance of the association not being real but simply due to chance is low (less than 5%). On the other hand, we could make the opposite mistake: we could have missed something real. A measure of the probability of not missing a true association is given by the "power" of the test. In general, the larger the dataset, the higher the power of the test; however, the smaller the effect one is trying to detect, the lower the power. Therefore, if a rare variant does affect the risk of a certain disease, a very large dataset is needed in order to have enough power to detect the association.

In less than ten years sequencing technology has improved steadily and genotyping costs have decreased, allowing researchers to genotype many more people. Furthermore, though SNP association studies have been very informative, they still haven't answered the question of the missing heritability: a large portion of hereditary traits (including diseases) are not explained by known associations.

Bottom line: this has shifted the interest back to the "rare" variants, SNPs whose MAF is less than 0.5%.
"Rare and low frequency (MAF between 0.5%-1%) variants have been hypothesized to explain a substantial fraction of the heritability of common, complex diseases. [...] Common variants explain only a modest fraction of the heritability of most traits [1]."
Tennessen et al. sequenced 15,585 human protein-coding genes from over 2,000 individuals of either European or African ancestry, and identified more than 500,000 single nucleotide variants, 86% of which were rare.
"This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits."
In the last few thousand years populations have experienced a rapid growth that had likely gone undetected in previous studies due to small sample sizes. Most rare variants (58%) found by Tennessen et al. were population specific and nonsynonimous, meaning that they yielded different amino acids. Surprisingly, this study found that "the vast majority of protein-coding variation is evolutionarily recent, rare, and enriched for deleterious alleles. Thus, rare variation likely makes an important contribution to human phenotypic variation and disease susceptibility."

In the next couple of years we will see more and more studies looking at associations between rare variants and diseases using 454 and deep sequencing technology. Many more rare variants will be discovered and the question will be to find the meaningful ones that rise above the background noise.

[1] Tennessen, J., Bigham, A., O'Connor, T., Fu, W., Kenny, E., Gravel, S., McGee, S., Do, R., Liu, X., Jun, G., Kang, H., Jordan, D., Leal, S., Gabriel, S., Rieder, M., Abecasis, G., Altshuler, D., Nickerson, D., Boerwinkle, E., Sunyaev, S., Bustamante, C., Bamshad, M., Akey, J., , ., , ., & , . (2012). Evolution and Functional Impact of Rare Coding Variation from Deep Sequencing of Human Exomes Science DOI: 10.1126/science.1219240

Sunday, June 10, 2012

OpenLab 2013 and Kreativ Blog Award

The Beast, the Bard, and the Bot honored me with a Kreativ Blogger Award. I confess I wasn't familiar with this award and, besides being pleasantly surprised, I was very happy to add The Beast, the Bard, and the Bot to my reading list as well as the other blogs he nominated. It's a wonderful way to get to know other blogs, because when you are nominated, you have to say seven things about yourself and nominate seven other blogs for the award.

First, my nominees (in no particular order, since they all rock):
In the company of Plants and Rocks
Interesting Things
Panda's Thumb
Lab Rat
Rule of 6ix

Before I get to the second requirement, I want to remind everyone that Open Laboratory 2013 is now accepting submissions! You can see the current submissions here and you can nominate your favorite science blog posts using this form.

So, the seven things about me/this blog:

1. I started blogging in July 2011, after much debating whether I should do it or not.

2. Total number of pageviews since July 2011: 48,140.

3. I'm not a biologist. My training is in mathematics and biostatistics. All the biology and genetics I know I've learned by doing research in computational biology since 2004 (cancer epidemiology from 2004 until 2006, and mathematical modeling and viral genetics afterwards).

4. I bought my DSLR in 2010. Writing and photography are my creative outlets.

5. Favorite music: Jazz.

6. Favorite writers: Gabriel Garcia Marquez, Hermann Hesse, Raymond Chandler, Eugenio Montale.

7. Favorite artists: Vincent Van Gogh, Leonardo da Vinci, Michelangelo, Rene' Magritte.

Thursday, June 7, 2012

Convergence of phenotypes: homoplasy

Most often, trait similarities between different species are an indication of a common phylogeny (homology). However, the opposite is also possible: independent phylogenies can indeed show similarities due to convergence in evolution rather than relatedness. When this occurs, a phenomenon called "homoplasy", it becomes of interest understand what mechanisms determined the convergence in phenotype.
"Study of the underlying developmental genetic mechanisms may reveal whether the recurrent structure has evolved via a novel mechanism or whether the ancestral mechanism has been deployed repeatedly [1]."
When similar traits are observed, a phylogenetic analysis can determine whether or not the similarities are due to homology or homoplasy: if the phylogenies are related, then the similarities have been inherited from shared ancestors. If, however, the genes are discordant, then the traits have emerged independently through homoplasy. This can happen at different levels, depending on whether it's through different mutations of the same gene, different genes, or different gene functions. These paths are not necessarily mutually exclusive, but they are hard to recognize.

Similar selection pressure on different species can cause homoplasy. As an example, in [1] Wake et al. mention two only distantly related species of lizards in White Sands, NM, that have independently evolved a blanched pigmentation. Other examples involve completely different genes that end up conferring the same phenotype. Petals in plants have evolved independently numerous times, and yet, despite the great variation they present in color, shape, and size, they always present conserved characteristics, in response to genetic and developmental constraints. In both vertebrates and invertebrates, eyes have gone through similar mechanisms:
"All eyes, invertebrate and vertebrate, develop through a cascade of similar transcription factors despite vast phylogenetic distances. These networks include genes (e.g., Pax6) that have been deployed in different ways at different times, and specific pathways that have re-evolved in different lineages by mutation, gene duplication, and intercalary evolution."

[1] Wake, D., Wake, M., & Specht, C. (2011). Homoplasy: From Detecting Pattern to Determining Process and Mechanism of Evolution Science, 331 (6020), 1032-1035 DOI: 10.1126/science.1188545

Monday, June 4, 2012

How the immune system recognizes danger from non-danger

There are three types of possible relationships between two different organisms: parasitism is when one benefits from the other, but the other is harmed; mutualism is when both benefit from the relationship; and, finally, commensalism is when one organism benefits and the other is neutral (neither harmed or benefitting). There are roughly 10^12 bacteria in our body. These are "commensal" microbes, because they live in our body without harming us. However, our immune system is trained to recognize "self" from "non-self", so a natural question to ask is: how come the immune system doesn't attack the skin and gut microbiota? In the guts especially, how does the immune system know how to distinguish the numerous pathogens we normally ingest through foods from the beneficial microbes that are fundamental in aiding digestion and nutritional assimilation?

It turns out that what the immune system does is far more complex than recognizing self from non-self. It's become a motto of mine, isn't it, how things are always more complicated than we think they are!
"Bacterial associations with their hosts can be beneficial, damaging, or benign, depending on the context and the identity of players. A host determines the balance of non-self elicitors and danger signals to decide when to activate the immune system against pathogenic infection while also maintaining healthy relationships with commensals [1]."
These interactions are mediated through a class of molecules, called "microbe-associated molecular patterns," or MAMPs, that are present in bacteria and are recognized by the host's immune system. Immune models studied in both insects and vertebrates suggest that both MAMP and danger signals are required to trigger a strong immune response, as shown in the figure below [Credit: Science Magazine]:

While both true pathogens and symbiotic microbes present MAMPs molecules, true pathogens also trigger "danger" signals by damaging host cells or secreting molecules that interfere with host biology.
"Studies in insect model systems suggest that the joint presence of both MAMPs and danger signals may be required to launch a true defense response and that insects have mechanisms for disregarding MAMPs presented in the absence of pathological damage to the host."
Interestingly, these findings suggest that rather than being mutually exclusive, MAMPs and danger signals are read together in a combined signal that helps the immune system decide not just whether or not to mount a response, but also the strength of the response itself. This way, the immune system is able to maintain a homeostatic equilibrium in maintaining a healthy level of symbiotic microbes, and also in dosing the strength of immune response.
"Rather than striving to completely eliminate infections, the immune system might manage a persistent infection at a low and nondamaging level. [...] MAMPs indicate the presence of microbes, but if the microbes are doing little or no damage to the host, the cost of immune activity may exceed the benefit of clearing the infection."

Lazzaro, B., & Rolff, J. (2011). Danger, Microbes, and Homeostasis Science, 332 (6025), 43-44 DOI: 10.1126/science.1200486

This post was chosen as an Editor's Selection for