Heights! Mapping the "Toy" Gene

Domesticated dogs are amazing in their variety - pocket size Yorkshire terriers to Great Danes! Ever wonder what accounts for that disparity?

Wonder no more. This week's issue of Science sees a study published that gives us a clue to how a mutation in a single locus regulates size in these creatures.

A team of more than 20 scientists from eight institutions (United States and the U.K.) toured the dog show circuit and collected blood from 3,241 canines of all sizes and shapes. They found that the reduced growth mapped to a locus, near the IGF1 gene. In human IGF1 plays a role in the growth from birth till adolescence.

In all the "toy" dogs tested (distantly related and reproductively isolated), there were mutations in the region next to IGF1. This is intriguing to see a single change map to all the small breeds, indicating that the change probably maps to the time when dogs evolved from their wolf-like ancestors. The same "small dog marker" however, is not found in the modern wolves.

Why is this so fascinating? Mostly because the entire study pinpoints a single allele to be responsible for the phenotypic variation (small size) and the result was achieved without doing a single cross!!

Longevity- What needs improvement?

S. Jay Olshansky, Robert N. Butler, and Bruce A. Carnes ask a simple question, What if Humans were designed to last? in the latest issue of The Scientist.

A coordinated network of molecular processes providing cells with nearly flawless surveillance, maintenance, and repair capabilities exemplifies the "perfection" of the human body. Living things need this precision in order to survive to reproductive
maturity in the face of a hostile environment and the toxic debris that the
cellular machinery of life generates. Meanwhile, subtle changes and imperfections at every level of biological organization give rise to the diseases and disorders associated with aging and impose limits on the duration of life, but ultimately, these changes and imperfections drive the evolutionary process itself. The juxtaposition of Michelangelo's perfection and Darwin's flaws embodies the linked stories of reproduction and death..

I particularly like that the authors say,

Our goal is not to create new methods of combating disease, but rather, to
spark an idea, trigger a thought, and inspire others to think outside the box by
first imagining a new future of human health that is better than the present -
and then working to make it so.

What do you think? If you could embark on making a long lived perfect human what would you change and why?

Discuss!

A Species Concept...How hard could it be??

People have thought about the origins of closely related species for decades. In fact, scientific research on speciation can be traced all the way back into the early 19th century. By looking at older literature, we can understand old arguments, as well as, provide us with ideas toward current problems. The evolution of biology is a like a history of unanswered problems that have been worked on by some of the most original thinkers of our time. This is very different from a field like molecular biology, where much of the older literature may be irrelevant due to advancement of the field. One of the first things that you should know is that researchers cannot come up with one universal definition of a species. Speciation is a process that can be looked at from many points of view, whether it be by Behaviorists, Phylogeneticists, Systematists or Evolutionary biologists. So, when trying to decide on a single definition, many conflicting ideas come into play depending on the angle you are examining it from. Most often, the definition for a species, depends on the specific criteria you have set for boundaries. As you can see, this is not as easy to define as it initially seemed. So, how do we begin to understand speciation? First and foremost, it is best to understand the current definitions that are accepted for a species. Then, tackle the problem of understanding the difference between concepts to finally be able to choose a definition that works best for you. Species Concepts for Speciation: 1. Biological Species Concept (Isolation Concept) (BSC) "Groups of actually or potentially interbreeding natural populations which are reproductively isolated from other such groups" (Mayr 1963) "Systems of populations, the gene exchange between these systems is limited or prevented in nature by a reproduction isolating mechanism or by a combination of such mechanisms" (Dobzhansky 1970) 2. Recognition Species Concept "The most inclusive population of individual biparental organisms which share a common fertilization system [specific mate recognition system]" (Paterson 1985) 3. Cohesion Species Concept "The most inclusive population of individuals having the potential for phenotypic cohesion through intrinsic cohesion mechanisms [genetic and/or demographic exchangeability]" (Templeteton 1989) 4. Phylogenetic Species Concept (Character-based) "An irreducible (basal) cluster of organisms, diagnosable distinct from other such clusters, and within which there is a parental pattern of ancestry and descent" (Cracaraft 1989) 5. Genealogical Species Concept "exclusive' groups of organisms, where and exclusive group is one whose members are all more closely related to each other than to any organisms outside the group..." (Baum and Shaw 1995) 6. Evolutionary Species Concept "A single lineage of ancestor-descendant populations which maintains its identity from other such lineages and which has its own evolutionary tendencies and historical fate" (Wiley 1978) 7. Genotypic Species Cluster Definition "Distinguishable groups of individuals that have few or no intermediates when in contact..." "...clusters are recognized by a deficit of intermediates, both at a single loci (heterozygote deficits) and at multiple loci (strong correlations or disequilibria between loci that are divergent between clusters)" (Mallet 1995) From this list, 1-3 are process based, while 4-7 are pattern based. Many researchers are adamant that pattern not process should form the basis of any species definition while the others are just as adamant for the opposite. A generally defined and consistently applied definition of species is vital for the study of diversity, as well as, phylogenetic investigations of diversification...which ultimately gives valuable insights into the study of speciation. However, what previously seemed easy to define, is in fact a hot issue being debated to this day... with the science community still not using a single, general concept of what exactly defines a species. I hope this opens up conversations as to what is a species, as well as, leads to interesting topics of speciation. I have given a foundation....so off you go now...

Do We Or Don't We?

Carl Zimmer brings up a very important point that conservation biologists (and all the rest of us who care about this Earth) are facing right now. As climate changes occurs, species move away in search of their natural habitats (as previous records show). However, we now know there are several species that might die if we don't find them a habitat.
The pros for human assisted moves are obvious - we save a threatened species. The cons are numerous - such moves in the past have rarely succeeded, when they did it resulted in threatening the natural habitat where the species was moved or it end up producing "hybrid zones" to name just a few.
As Zimmer puts it, "Which is worse: the risk of creating a new invasive species through assisted migration, or just watching a species become extinct? "
We have a moral dilemma in front of us - I wonder what step to take?

What We Cannot See Threatens More

So many people talk about terrorism with an idea of people in mind. We seem to concentrate on nuclear threats and how it will bring the demise of our human race. Since I am not able to foresee the future, I cannot eliminate this possible threat in the future...but in my view...I do not believe this to be the most imminent threat to our race. That is not what scares me.... With each piece of knowledge that I acquire, I am scared of the terrorists that I cannot see. The silent killers. The millions of microbes that have the potential to do more harm, in more places, at the same time, than any nuclear bomb. We live in a time when travel and international business is the way of the world. We move around so often and so quickly, businessmen often forget where they have been on a given trip. I applaud progress and fair business, but I also am afraid of what else travels along on these trips with any given person from place to place. People come into contact with organisms in new environments in which they have never been exposed and then in turn infect 10's if not 100's of people in a single afternoon. Imagine the number of people you are near at the O'Hare airport in Chicago or Grand Central Station in NYC. Try to quantify the trail of contact of each person you are near...and ultimately where they go. The numbers are astounding and you feel as if you can't possibly tackle something this big. So, why do I call these microbes terrorists? That is simple. These microbes or whatever the latest attack is, is invisible to the naked eye, it evolves faster than we can sequence it, symptoms may seem like the common cold and does not have the ability to rationalize. We cannot sit in a room with these invaders, sign a treaty no one has any intention of keeping and walk away feeling like we have control. We are at the mercy of these invaders. You may be wondering why this is a problem now more than ever in the past. Research and reports have been published explaining why we are at a greater risk now of new pathogens emerging. First and foremost, we are dealing with microbes that have "tremendous evolutionary potential". We are also faced with so many other things such as "changing climate, altered ecosystems, increased human contact with animals, new medical technologies that have created novel pathways for the spread of infections, and 'the rapid and virtually unrestricted transport of humans, animals, foods and other goods, which can lead to the broad dissemination of pathogens and their vectors throughout the world'". We are sharing and trading microbes into new environments not previous occupied. This is and will be an action that carries harsh consequences. "Any of these factors alone can trigger problems, but their convergence creates especially high-risk environments where infectious diseases may readily emerge, or re-emerge...It is conceivable, in fact, that in certain places microbial 'perfect storms' could occur, and unlike meteorological 'perfect storms,' the events would not be on the order of once in a century, but frequent." We have in recent years experienced such occurrences that could have been much worse than they were, (i.e., SARS, avian bird flu, west nile). As we learn more with each passing day and from past epidemics, we must work together not as a country or countries, but as a race, to face such obstacles. In the example of SARS, the result could have been devastating. One country, China, hid the outbreak for many weeks if not closer to months. Politics and tourism blinded what was truly important...its' people. Once the knowledge of a new epidemic hit the WHO, global cooperation began the process to stop the impending devastation. It is only due to laboratories around the world, working tirelessly for a common cause, that we are not writing about entire countries being wiped out. By May 17, 2003, the WHO reported 7,761 cases of SARS around the world with a death toll of 623. This was spread across 28 countries on 5 continents. Of those, 66 cases were in the US (no deaths), 5209 cases in mainland China with 282 deaths and 1710 cases in Hong Kong with 243 deaths. Although the number of cases seem high, the low number of deaths is due to a few dedicated and active people that rallied early to stop this from spreading even more. They were successful in their efforts of containing the cases early. However, an expert in human diseases caused by parasitic worms and a tireless foe of infectious diseases, a doctor once part of the doctors without borders and one of the doctors that preached, "stay close to the victims", did just that. Carlo Urbani stayed close to the first victims of SARS. He monitored them himself and rid the area of unnecessary people that could be at risk. Urbani also was the first to act and begin to gather the people necessary to alert the world. Unfortunately, it was only a matter of time before he too fell victim to this outbreak. Urbani died with his wife and 3 sons following behind his casket. The SARS virus was so infectious that even another week's delay in recognizing the problem would have spread the germ to hundreds if not thousands more people before control measures were put into place, one nation at a time. This is what Urbani did for all of us. His quick action had limited the number of cases and his doctors said he had probably inhaled so much virus as he tried to treat so many people that he was doomed from the start. I write this as an introduction to the continuing story of what really threatens us. We do not have any idea of what or where the next big terrorist will come from, or even the ability of science knowledge to combat it. I do not fear other nations and the weapons they hold as much as I fear microbes that can appear and evolve faster that we can identify common links. Researchers wait with dread of that never previously seen microbe that has the ability to jump across the animal-human line. This threat, in addition to combining with common viruses that we cannot control now, is what scares me!

References:

http://www.cdc.gov/ncidod/sars/factsheet.htm

http://content.nejm.org/cgi/content/full/348/20/1951

http://www.who.int/en/

M. Enserink, "A second suspect in global mystery outbreak". Science 299 (March 28, 2003)

M. Hamburg, J. Lederberg, B. Beatty, et al. "Microbial threats to health: Emergence, detection, and response" Institute of Medicine National Academy of Sciences. Namtional Academies Press, March 2003.

Ashley Treatment - Right or Wrong?

Ashley Treatment is making waves in medicine. A young girl with static encephalopathy (severe brain damage) has undergone an operation to stunt her growth and keep her at a manageable size. This has created a big hue and cry over the net all over the world with some parents even linking it to eugenics.
When I first heard about the case I got squeezy too. I have been a fringe dweller in the world of autistic and mentally retarded people. My parents are actively involved in this cause back home and I have seen how difficult it is to take care of a 6 feet 2 adult with a mental capacity of a 2 year old. As difficult the situation is, parents rarely have thought of taking such extreme steps. So I wondered, Is this right? There are no medical precedents to this case. This may very well open up a slippery slope as pointed out by University of Pennsylvania ethicist Art Caplan. But let us look closely at the "pillow baby Ashley" case before we raise our voices to say this is wrong -
Shortly after birth, baby Ashley had problems feeding and lagged in development. Doctors diagnosed static encephalopathy (and still do not know the cause). The brain damage has left her in an infant stage - she is for all purposes a 3 month old - unable to hold her head, sit, roll or walk or talk and yet she is four feet five inches tall. That being said the girl is alert and goes to school for disabled children. However since her parents have not found a suitable care taker, they tend to the child at home themselves. There is no cure for Ashley (now and in the near future). She is going to be in the same state yet continue to grow bigger.
So her parents decided to stunt her growth to keep her smaller. She had her uterus and breast tissue removed and she received large doses of hormones to halt her growth. This will keep her small, reduce risks of bed sores and prevent her going through puberty (reducing the pain of periods and breast cancer which runs in the family). Her parents are taking care of her. Keeping her from growing is not going to make a difference to her - she is 3 month old mentally!!
Medical advances have meant that we can "save" lives that previously would not have a chance. At the same time, we really do not have the capacity to take care of severely handicapped people. Nor do we have a better support system for families that take care of the individual on a daily basis - 24/7. Some ethicist that say what Ashley's parents are doing is making the situation easy on themselves - yes, they are .. but try taking care of a infant that weighs like an adult for a whole day! You might change your mind too. On the other hand, the question to be asked is - who decides that this is the right thing for the parents to do? Take this scenario - What if a slightly challenged girl's parents decide that to save her from abuse in the future, we are going to prevent her from undergoing puberty. This girl is always going to be a minor legally. So do her parents have legal rights? Or should society intervene?
But society is not making the place safer in which case the parents would never have to make such decision. Realistically speaking, man kind is not going to make this earth into an Utopian paradise . Does this mean that this decision or others like it would be ethical?

Book Review

Another good book by Carroll. Making of the fittest explains evolution using the evidence found in the DNA of every creature. Using DNA as evidence, Carroll weaves stories that tie creatures together and spin across millions of years and clearly explains how identical traits have evolved independently(and sometimes repeatedly) by natural selection.

The examples themselves are fascinating - evolution of anti-freeze protein in Artic and Antarctic fishes, color vision through duplication of Opsin genes in birds and primates, sickle cell anemia and resistance to malaria, eye development (an creationist favorite) to skin color in humans. In each case, Carroll explains the genetic changes that the DNA has undergone over the course of time to result in the developmental changes we see.

He has also explained how inaccurate is the creationist insistence that probability of mutations resulting in evolution is next to impossible. He uses very elementary mathematics to explain how advantageous mutations can spread through a population.

Carroll has also tackled head on the problem the US schools are facing now -the disingenuous ID believers who want to teach "creationist science" (which is an oxymoron). Using the Lysenko fiasco as an example, he has clearly illustrated what can happen if there is a deliberate ignorance of evidence.

Unlike Zimmer, reading Carroll does require some basic understanding of biology (high school level at least) but he is an adept writer and worth reading. It is a book aimed at curious people who would like to know more about Evolution and the evidence we have for it. I don't think Creationists or the IDiots are going to change their minds but I hope books like this one convince the fringe dwellers that Evolution is more than a "just" a theory. There are numerous examples of evidences - from geology to now molecular biology- to show how evolution has occurred. As Lewis Black said "We have Fossils. We win."