Biochemical Soul Musings on Nature, Science, Evolution, Biology, and Education


Darwin and the Heart of Evolution

Happy 200th birthday, Charles Darwin!
Happy 200th birthday, Abraham Lincoln!
Happy 150th anniversary, On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life!
And here's to a happy Darwin Day and upcoming Valentine's Day to everyone else.

As a part of my own contribution to the Blog for Darwin campaign, I present to you "Darwin and the Heart of Evolution."

What do all four of the above events have in common, other than being events of celebration? The answer will become obvious, but as a clue, I will begin with an appropriate Valentine's question:

A Frog's Heart

A Frog's Heart

Why do humans have hearts?

I can see it already – you’re rolling your eyes thinking, “Well duh…because we need a way to circulate oxygen, hormones, immune cells and other signals, and transport waste compounds and gases.”

Ahh, but you would be wrong. For the above describes only what a heart does – not why we have one. As I wrote a few days ago, evolution pays no attention to "needs." Species don't evolve because they "need" to adapt or change some trait. Natural selection is blind to all intention and desire.

Before Charles Darwin (and his buddy Alfred Russell Wallace) gave us the theory of natural selection, the above "necessity" explanation would have sufficed – with an added “because God designed it that way” just for good measure.

The genius, beauty, and simplicity of Darwin’s big idea was in how it utterly reshaped the manner in which all “why” questions about reality are posed and how their answers are understood. The Origin of Species laid the foundation for the complete upheaval of the very word “why.” In fact, when it comes to describing biology, astronomy, physics, geology, and every other empirical look into reality, the word “why” now means nothing more than the word “how.” The how is the why.

So again, I ask - why (how) do humans have hearts?

To answer this question we need to jump back about 500 million years ago into the ancient ocean. Based on the fossil record, this is a good date to pick, considering that worms don’t make great fossils; however, the exact date is not at all important for this discussion. Nor does it matter the exact species of worm-like creature we consider, or the exact details of the hypothetical time-traveling adventure upon which we will now embark.

Imagine it - we’re swimming now in the ancient ocean sometime after the massive explosion in the evolution of all sorts of strange ocean-dwelling invertebrate body forms (the Cambrian explosion). One of the many advantages that certain individuals of various species find is that their larger body sizes makes them better able to compete – up to a point. Once a small early worm-like species reaches a certain size, it finds that it cannot grow any bigger with its current body plan. This is because at this point, our hypothetical creatures do not have circulatory systems. They must absorb all their oxygen from the surrounding water. Any individuals born larger than a certain size can no longer get enough oxygen due to the oxygen not reaching deep enough into their tissues, and so they die (or are our-competed).

The Vertebrate Family (image credit)

The Vertebrate Family

Now imagine an individual of this species is born with what others of its species would consider a defect (if they had brains with which to consider such a concept). This individual has certain cells that have formed a small simple tube-like structure. Perhaps it is only a vague cavity – or some extra space between its cells. Now when this individual swims around, contracting its primitive muscles, the fluid within its body spreads a little bit more and a little bit faster through this cavity or space.

Our little worm leads a happy life, finding mates (or perhaps reproducing asexually) and leaving an ocean full of cavity-containing offspring. It seems self-evident to us now, but Darwin found himself surprised at the amount of variability in traits throughout the animal kingdom. All populations vary; thus, some of our worm’s children are a little bit bigger than their siblings. And some of these worm children will have inherited papa worm’s fluid cavity, which meant that they could survive with a slightly larger body than those without the primitive vessel, due to the oxygen distributing power of the fluid filled vessel.

Thus began the evolution of the heart. By a series of easy to imagine steps through thousands or millions of generations, the cavity became slightly more developed, eventually forming an actual tube. I would like to note here that the above scenario is strongly supported by much embryological, anatomical, and genetic data. However, I would like keep this simple and vague for the layperson.

Now, we move forward in time, though how far is unclear. Our little worms are now bigger worms, insect ancestors, and a myriad other small invertebrate species. Some of these species have evolved their tubes to have contractile regions - that is, a region of the tube than can actually squeeze and pump. Some, like our modern earthworm, have seven of these pumping “hearts”. Others, like the Drosophila fly, have only one heart - called a "dorsal vessel" (see the Drosophila larvae movie below).

Fish Heart

The Fish Heart

We swim forward to 525 million years ago, just as the first fish appear in the fossil record. A lineage of the invertebrates has slowly morphed through primitive chordates (organisms with a nerve cord) to become the most primitive fishes. Along with the changes in many other body structures, the basic contractile heart and vessel system has itself become more complex. Instead of one contractile chamber, the fish heart has divided into two chambers: an atrium and a ventricle (and a stretchy region called the conus that isn’t contractile). The fish themselves then radiate over time, each lineage slowly accumulating many small changes, resulting in the gradual evolution of an ocean teeming with fish species – all with two-chambered hearts (see image at right).

Eventually, some fish species start shacking up near shorelines or in shallow ponds and lagoons. Some are born with thicker fins, which allow them to push along the bottom of the pools a little more quickly or lithely than others. They mate, and the process continues. Finally, one of them decides to just get it over with and leaps out of the water to land as a frog on four fully-formed legs.

The Amphibian Heart

The Amphibian Heart

Not really, but you get the picture.

We now see amphibious creatures roaming the shorelines like beastly salamanders. Their hearts have changed even further as other aspects of their bodies evolved to take in oxygen through lungs. Why did this happen? Because the changes that make it possible did happen. These shallow water-dwelling creatures began to develop vessel-filled outpockets on their esophagus, giving them the advantage of pulling oxygen from the air. In addition, the individuals with slightly better circulatory systems found their bodies better at all sorts of other things, such as regulating their bodies with hormones and getting rid of cellular wastes.

At this point, a series of further changes occurred in the amphibian heart. The atrium became two separate atria, either through a physical division of the one atrium, or through a duplication of the vessels coming into the heart. Thus, the frog ancestors developed three-chambered hearts, which were subsequently passed down to every frog currently inhabiting the earth (see image).

The Reptile heart

The Reptile heart

As time passed, the frogs began drying off their slime, sprouting scales and forked tongues, and inspiring instinctive reptilian nightmares in their prey. They became lizards. As the lizards moved fully to land and grew even larger, certain inherited variations in their hearts naturally worked a little better – thus natural selection continued the continuous sculpture of life. The ventricle began to separate into two chambers, much like the atrium had done in the amphibians. However, the ventricles didn’t fully divide. As one can see in almost every reptile on earth today, the ventricular division is incomplete – almost like a four-chambered heart, but with a hole between the ventricles (see image). However, I said that almost all reptiles have the pseudo four-chambered cardiac morphology; in fact, one branch of the reptiles went on to develop a fully-featured, true four-chambered heart: the crocodile - but that's a side story.

From some of the lizards the dinosaurs then sprung forth, populating the land from the small dark corners to the open plains. A short while later (a paltry 170 million years) most of the dinosaurs died off. Along with their distant crocodilian, lizard, and snake cousins, at least one dinosaur lineage and one reptilian lineage survived. We now call them birds and mammals, respectively.

Both the bird and mammalian lineages mirrored the path of the crocodile, completing the division between the ventricles (probably prior to their divergence). Natural selection has continued to sculpt our own mammalian hearts, resulting in marvelous structures such as the multiple different valve types, chordae tendenae ("heart strings"), and trabeculae (fibrous strings in the ventricle's interior).

The Bird and Mammal Heart

The Bird and Mammal Heart

And with that, we have answered our initial question, in a massively oversimplified fashion. We have hearts because each change leading to our hearts conferred some small advantage to the individuals that inherited them (or at the very least, were not disadvantageous).

Of course, all of these cumulative small changes in the shape of the vessels and hearts, ultimately involved millions of small changes in the genes that controlled the behavior, shape, and functions of the circulatory cells. Scientists have now discovered an incredibly large and complex network of such genes controlling development of the heart.

One of the most astonishing yet completely expected facts we have garnered through studying organisms from Drosophila to the African clawed frog (Xenopus) to humans is the discovery that every organism on this planet with some version of a heart contains the same or a similar set of genes to control heart development.

That’s right. Read it again.

Many of the genes involved in the formation of the relatively primitive “dorsal vessel” in a fly are versions of the same genes that initially form our own hearts. Think about that! Think about how massively more complex we are compared to flies (which are themselves insanely complex in their own rights). Think about the hundreds of millions of years that separate us from our most recent common ancestor with a fly. Yet your heart still uses many of the same genes and in the same ways during early heart development. Of course flies and humans have continued to evolve in parallel ever since our lineages split those hundreds of millions of year ago – we have both made countless changes and tweaks to our own cardiac programs and networks. Nonetheless, our hearts remain related.

In fact, if you watch heart development in an embryo, such as in the Xenopus movie below, you can almost see the course of heart evolution itself. Of course this isn't really ontogeny recapitulating phylogeny - but some of the evolutionary history behind cardiac development is at least evident.

Tbx20 expression in a frog larva heart

Tbx20 expression in a frog larva heart

One example of a cardiac gene that I’m particularly familiar with, having received my doctorate studying it, is a gene called “Tbx20”. For this discussion, its exact function does not matter. Suffice it to say that when I began my studies, we had a clue that this gene was important in heart development. Why? Because flies have a copy of this gene, as do humans, mice, and every other heart-bearing organism we’ve looked at; furthermore, in each of these organisms this gene is “turned on” in the developing heart tissue.

I went on to show that when you prevent frog larvae from making the Tbx20 protein, they develop incredibly malformed hearts (see the videos below). This means that the Tbx20 gene is indeed important in making a heart. Other researchers later went on to show similar results in mice and flies. Finally, about two months before I finished graduate school, another group of researchers found that some humans born with congenital heart defects have mutations in the Tbx20 gene.

Normal African Clawed Frog (Xenopus) heart

African Clawed Frog (Xenopus) heart lacking Tbx20 protein

So here we have found in only a few years of research a single gene that supports the entire model of evolutionary theory. To rephrase the famous quote from Theodosius Dobzhansky, the existence of Tbx20 in controlling the development of the heart in organisms from flies to humans does not make any sense – except in the light of evolution.

Due to the rich evolutionary history behind the development of this complex organ, the genetic network has become incredibly complex, involving hundreds of genes in thousands of cells all working, moving, and functioning in precise coordination. The higher the complexity, the more things that can possibly go wrong. Unsurprisingly, congenital heart defects are among the most prevalent of all inherited diseases, resulting in about 9 babies out of every one thousand being born with some sort of cardiac abnormality.

I’m sure many of you were wondering how I would manage to tie Abraham Lincoln tie into all this. Although still hotly debated and unproven, at least some researchers believe that Abraham Lincoln may have been afflicted with a disease called Marfan Syndrome, a connective tissue disorder affecting the heart and many other organs. Other researchers believe that he had an unrelated disease. Regardless, it remains at least possible that President Abraham Lincoln was the inheritor of one of the billions of less advantageous variances in heart development that have presented themselves throughout the heart’s evolutionary history.

In summary, the heart of Darwin's theory of natural selection is the idea that evolution comes not through the "why." It comes through the how - through the accumulation of minute individual variations that spread like wildfire when they contribute an advantage.  There remains no better demonstration of this principle than the myriad heart morphologies and functions we can trace today.

Each of you has most certainly inherited a cardiac variation, whether it be a major mutation in a gene, or a tiny change in one letter of your genetic code (a "single nucleotide polymorphism").

Who knows...perhaps yours is the one upon which an entirely new evolutionary history will be built.

So here’s to your own personal variation, and to the man who made our understanding of it all possible. We would have gotten there without him – but I doubt anyone could have rivaled the combination of his incredible intellect and beautiful prose.
Happy birthday Darwin!

Image credits

Frog heart photograph: Me
Phylogenetic tree: McGraw-Hill and Biology Corner
Drosophila heart tube movie: unknown
Heart diagrams: Oracle ThinkQuest Education Foundation
Cardiogenesis animation: Me
Frog heart movies: Me
Lincoln photograph: Visiting DC

Lincoln photo:


Evolution in Action: Fruit Flies Evolve Low Oxygen Tolerance in the Lab

Summary of alterations in signal transduction pathways.

Summary of alterations in signal transduction pathways.

ResearchBlogging.orgIn a cool new study in PLoS Genetics, through artificial selection researchers have allowed fruit flies (Drosophila) to evolve tolerance to normally lethal low levels of Oxygen.

To many scientists, this type of research will not be seen as that impressive, as a general finding. Artificial selection has been occurring for millennia, and it is the method through which we have created every domesticated animal and crop on the planet. Scientists will however find the specific genetic changes and biological pathway changes involved in this microevolution fascinating indeed. But it serves one more example (among mountains of others) of evolution being witnessed and directed under laboratory conditions.

Personally, I think one of the most amazing aspects of this study was just how quickly these flies evolved to survive and develop perpetually in severely low oxygen conditions. In only 32 generations the flies were able to live in oxygen conditions completely lethal to normal flies.

After they generated the flies, they did whole genome analyses to figure out exactly which DNA sequences and enzymatic pathways had changed in sequence or expression to result in this tolerance, including (not surprisingly) cellular respiration enzymes, citric acid cycle enzymes, and major signaling pathways, such as EGF, Insulin, Notch and Toll/Imd pathways.

Their goal is to eventually apply this information to mammalian systems to understand our own reactions to low oxygen states such as the “reduction in oxygen delivery at high altitude or during certain disease states, such as myocardial infarction and stroke.”

So yes, Sarah Palin, fruit fly research is good for something.

Dan Zhou, Jin Xue, James C. K. Lai, Nicholas J. Schork, Kevin P. White, Gabriel G. Haddad, Eric Rulifson (2008). Mechanisms Underlying Hypoxia Tolerance in Drosophila melanogaster: hairy as a Metabolic Switch PLoS Genetics, 4 (10) DOI: 10.1371/journal.pgen.1000221


Sarah Palin knows nothing of science

Fruit Fly Brain

Fruit Fly Brain (credit Pamela Mitchell)

In one of the single most maddening, ignorant, unfathomably idiotic statements (out of many) I have heard spew through Sarah Palin’s lips, the candidate for the second highest position in the free world uttered a single phrase today that could utterly destroy the progress of medicine and scientific understanding.

In her very first policy speech, Palin talked about autism and disabilities (video below). She urged that

“For many parents of children with disabilities, the most valuable thing of all is information. Early identification of a cognitive or other disorder, especially autism, can make a life-changing difference.”

This is very true. And where does this information and the ability for early identification come from? Scientific research. Unfortunately, she went on to say

“You’ve heard about some of these pet projects they really don’t make a whole lot of sense and sometimes these dollars go to projects that have little or nothing to do with the public good. Things like fruit fly research in Paris, France. I kid you not.”

When I heard this issue forth from my T.V. I literally could not believe what I had just heard. I had to rewind my TiVo just to make sure. I write now filled with more anger at the the current state of this union than I have felt in some time (albeit, anger cut with a good dose of hope).

Why the anger, you say? What’s wrong with her statement, you ask?

This statement of “public policy” exhibits an almost unbelievable level of the ignorance of Palin and those that support her – and on multiple levels.

Drosophila melanogaster

Drosophila melanogaster

#1. The fruit fly (Drosophila) has probably been the single most important organism for the study of genetics for over a century now. Almost everything we know about genetics, development, cell biology, neuroscience, and every other field of biology has strong roots in previous and current work on Drosophila. The fruit fly is one of a small handful of “standard model organisms” used by thousands of scientists across the world to learn how our bodies, organs, genes, and proteins work. Most of what we know about how a single fertilized cell becomes the amazingly complex beings we are comes from studies initially done in Drosophila. Vast amounts of our understanding of the brain (and brain disorders, diseases, and defects) also come from initial studies in fruit flies.

In fact, recent research from my own graduate alma mater, the University of North Carolina at Chapel Hill, on fruit fly brains has had an impact on the understanding of autism and has boosted autism research:

“[S]cientists at the University of North Carolina at Chapel Hill School of Medicine have shown that a protein called neurexin is required for..nerve cell connections to form and function correctly. The discovery, made in Drosophila fruit flies may lead to advances in understanding autism spectrum disorders, as recently, human neurexins have been identified as a genetic risk factor for autism.”

To decry research in [condescending and amazed tone] “the fruit fly” is a testament to the true idiocy of this woman and to the failure of our public education system. In fact, her own father, Chuck Heath, was a biology teacher – obviously a complete failure of a biology teacher.

#2. The fact that she threw in “in Paris, France” represents yet another tactic to pander to the “patriotic,” French-hating (remember Freedom Fries?) Right. It also represents another misunderstanding of the nature of science in the modern world. You see, science knows no borders. It doesn’t matter where the research happens. The results all end up in the same place – in our collective database of scientific knowledge.

In my own research, both current and past, my work on heart and brain development has been based on, and done in collaboration with, other scientists all over the world. Some of my current research is based on results from a group in Korea. Other projects were based on studies from a consortium of scientists from Canada to China to Australia.

Regardless of where the research is done, it all contributes to the “public good” and it all feeds into the knowledge of our biological existence, into the state of our medical technology, and into our mental and body health.

I’ve been fuming ever since hearing her comments tonight. I am now happy to say that both Keith Olbermann and Rachel Maddow are currently covering this story quite well on MSNBC. To quote Richard Wolffe on Olbermann's Countdown, this is one of her most “mindless, ignorant, uninformed, comments” yet.  I hope I don't need to spell out for you why having someone like this in the number 2 (or God forbid, number 1) position in the country will harm science and scientific undertanding in this country.

I imagine the science blogosphere will be alight with posts about this, hopefully from some actual Drosophila scientists, and I will update this post with their links as they come along (let me know if you want your blog post listed).

(Note: Please Digg this below, or use whatever bookmark sharing site you prefer - we need as many people to see this issue as possible).

Update: Welcome visitors from AmericaBlog! You may also enjoy this image.

Update 2: For those of you who understand that the details of the earmark (which I don't think Palin even had a clue about) actually deals with a different species of fruit fly (Olive Fruit Fly), see the comments section. Yes I am very well aware of this, but it has no bearing on her comment, apparent ignorance, and flippant dismissal of research because it deals with silly-sounding fruit flies. More: PZ Myers at Pharyngula blasts the claim that she "wasn't disparaging all research into fruit flies, but only one specific earmark for studying agricultural pests."

Other coverage of Palin's scientific ignorance:

Excellent post at Reasoning the Reasons: Does She Not Know? Or Does She Not Care to Know?

Think Progress: Memo To Palin: Fruit Fly Research Has Led To Advances In Understanding Autism

Daily Kos: Sarah Does Science

Blue Herald: Olbermann and Wolffe Discuss Palin's Mindlessness

The great PZ at Pharyngula: Sarah Palin: Ignorant and Anti-Science, Losing the Sense of the Argument

My Point Exactly: Science, schmience, part 2

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