Sickle Cell Saves Lives

Consider this: there is a genetic disease, sickle-cell anemia, that can affect as many as one out of every hundred people. It causes strokes and organ damage. It shortens the average life expectancy. The theory of natural selection would suggest that the mutation should eventually disappear, but it doesn’t. Why?

The answer is a quirk of genetics, evolution, and natural history. To understand why, you need to know that sickle-cell is based on an incompletely-recessive gene, meaning each parent needs to pass on a copy of the allele for you to develop the disease. It’s possible to have only one copy and be totally healthy – but there’s a caveat. Normally recessive genes are completely silent, but sickle-cell isn’t perfectly content to sit in a cell and play along. It still makes a little bit of the mutant protein responsible for the disease.

And this is actually the key to why it sticks around. In huge quantities the mutant hemoglobin proteins can ruin the cells, turning nice normal circular red blood cells into crescent-shaped sickles. The mutant cells can’t squeeze through blood vessels, causing blockages. But in small quantities the protein can actually be beneficial. Consider the following maps:

The map on the left is the distribution of sickle-cell alleles – high in central Africa and India, then tapering out towards the edges. The right is the distribution of another devastating illness – the parasitic disease malaria. It turns out that the mutant hemoglobin proteins, deadly in high doses, can actually help prevent the malaria parasite from surviving in your blood. The key is to have only one copy of the mutation, not two.

That’s why sickle-cell genes stick around in the population – the benefits for heterozygotes (one-copy) outweigh the evolutionary detriments to homozygotes (two-copies). This quirk is known as heterozygote advantage. Neat, huh?

Sources: Harvard.edu, Wikipedia

 

Remaking the Dire Wolf

Humans have been breeding dogs for at least 7,000 years, possibly as much as 30,000. During that time we’ve accomplished the most dramatic artificial selection known to history. From the utilitarian body plan of gray wolves we’ve expanded the species to include sleek whippets, pixie papillons, and stodgy bulldogs. We’ve even super-sized the creatures. The mastiff can weigh in more than a full-grown man.

The American Alsatian is another of these super-sized dogs. It’s not quite as big as a mastiff – the largest weigh only about 120 pounds – but its an intimidating animal. The dogs are have an intense profile, a massive stocky body, and a certain wolf-like stare to them.

Fetch?

And that’s exactly how they’re supposed to be, because the American Alsatian is more than a breed. It’s an experiment to see if artificial selection can go beyond domestication. If the breeders are successful, their dogs will be the closest living thing to a real live dire wolf.

The group is known as Dire Wolf Project, an offshoot of the National American Alsatian Breeder’s Club. Dire wolves (Canis dirus), a larger, stockier cousin to the extent gray wolf, once ranged throughout North and South America. They were the heaviest canids to ever exist, but went extinct along the other great megafauna roughly 10,000 years ago. The project was started in 1987 by a dog breeder named Lois Denny. She started the line with an Alaskan Malamute and a German Shephard, eventually working in other breeds such as English Mastiffs and Great Pyrenees. Their stated goal is to recreate the body plan and skeletal features of the extinct animal.

It’s worth noting that, since modern dogs are not actually related or descended from dire wolves, the American Alsatian is not recreating the animal. That would need some form of direct ancestry. All breeding has taken place through domesticated dogs. Furthermore, the breeders have placed a high priority on an easily trained, calm animal, not a wild one. Animals were selected not only for their look, but also calm temperaments.

On the one hand, this is an intelligent practicality, no one would want to own a large, unreliable animal. On the other, it is also somewhat admitting our own lack of knowledge. The social structure of dire wolves is mostly unknown. Most scientists assume they hunted in packs, but this isn’t known for sure. And without a living true specimen, we can never know for certain.

Nevertheless, it is hoped that the convergent body plans may help illuminate how real dire wolves would have grown, run, or hunted.

Sources: The Dire Wolf Project

 

Rosalind Franklin’s DNA

The field of science can be cruel. To the victor go the spoils and many times the lesser names get left behind. We remember the Darwins and forget the Wallaces.

Most anyone in biology can tell you that DNA’s structure was discovered by a pair of scientists named James Watson and Francis Crick. By the end of World War II, scientists around the world understood that genetic information was carried along by something known as deoxyribonucleic acid, or DNA, but nobody knew what the molecule really looked like. The famous double helix had not been discovered yet. The story goes that one day, the two scientists stumbled into the Eagle pub in Cambridge and Crick, giddy on scientific euphoria, announced, “We have found the secret of life.”

And they had. In a 1953 issue of Nature, Watson and Crick printed the now famous “Molecular Structure of Nucleic Acids”, a paper that would earn the pair a Nobel prize.

But this simple story ignores a name that some feel deserves equal credit, one Rosalind Elsie Franklin. At the time of Watson and Crick’s work, Franklin was a graduate student at King’s College London. She was studying the process known as x-ray crystallography, a complicated process wherein the structure of proteins is teased out of x-ray photographs. One of the proteins she was working on happened to be DNA. Apparently her advisor, Maurice Wilkins, had a strong dislike for the girl and, without her knowledge or consent, presented the visiting Watson and Crick with her imagery, which happened to be exactly the data they needed to confirm their suspicions. It was, “the data we actually used,” said Crick.

Watson and Crick’s paper barely hinted at her involvement, even though early drafts of Franklin’s own papers showed she was well on the way to discovering the double helix herself. The nature of this slight is contentious. Some claim Watson and Crick’s paper was near-plagiarism, others say the pair of scientists acted in good faith. It’s even been suggested that her snub was outright misogyny.

I personally stand with the view that the slight was as much an accident as anything else. There were a number of different competing teams working on this discovery and everyone had their flaws. Watson and Crick’s egos were legendary and both Franklin and her superiors could be bullheaded and secretive. In the end, everyone did get their say in the same magazine, it was simply Watson and Crick who said their piece first.

Still, it is worth remembering the biophysicist did do brilliant work and her data was integral to our understanding of genetics. There is a growing trend in the scientific community to say the discoverers of DNA were Watson, Crick, and Franklin, all in one breath. Perhaps not a bad one.

Franklin would go on to work on the tobacco mosaic and polio viruses, where she made foundational contributions. Franklin died in 1958 from ovarian cancer. She was 37.

Sources: RosalindFranklinSociety, Scientific American, Guardian UK, Nature

 

Horizontal Gene Transfer

Life is messy.

We are taught from a young age that evolution happens in one direction. As we move forward in time, genes are passed from parents to children, like branches on a family tree. We, the current generation of life, can sit high in the branches and look downward, smiling, at the unbroken line to what must have been the first genesis of life. A clean shot from cell to animal to human.

Except it’s not that clean. What I’ve just described is known as vertical gene transfer and is, for most of us, the primary means of moving genetic material. However, there’s also ways to get around this, to exchange information between currently living organisms. This is known as horizontal gene transfer.

A biological tree accounting for horizontal transfers

There’s a number of different ways this occurs. Bacteria can actually pick up and incorporate random exogenous DNA fragments (a process known as transformation) or conjugate and exchange DNA from cell to cell. Viruses can litter their hosts genetic code with leftover sequences from their original home. Cells can actually become trapped within other cells (a process known as endosymbiosis) and evidence suggests that DNA transfer occurs here too. Endosymbiosis is actually probably the reason your own human cells have mitochondria (and chloroplasts, if you’re a plant).

It’s quite likely that all of these were occurring at tremendous rates while life was first evolving. There was likely no first bacteria or eukaryote. Instead life truly was a ‘soup’, a fluid evolving community instead of distinct lineages. As Scientific American put it: “If there had never been any lateral gene transfer, all these individual gene trees would have the same topology (the same branching order), and the ancestral genes at the root of each tree would have all been present in the last universal common ancestor, a single ancient cell. But extensive transfer means that neither is the case: gene trees will differ (although many will have regions of similar topology) and there would never have been a single cell that could be called the last universal common ancestor.”

 

Island Quirks

For a biologist, if you want to find something neat you should go to an island. It doesn’t even have to be a real island, any isolated ecosystem can bring out evolutionary quirks, but for physical isolation you can’t beat a good, old fashioned miles-out-at-sea, coconuts-and-palm-trees island. The island effect isn’t always the same, but for perfectly weird, it’s hard to beat an island. So, in honor of islands, a couple examples:

Firstly, I’d like to point to a recent article by The New York Times about blonde Solomon islanders. About one out of every ten of these islanders has bright blonde hair, which is normally only found in Europeans. No other islands have this trait. Its prevalence is likely due to what’s known as the founder effect. Isolated gene pools tend to magnify any mutations present in the original colonizing population.

The second effect I’d like to highlight comes in the form of giant bunny rabbits. Known as Nuralagus rex, these bunnies were at least six times larger than modern rabbits and lived three million years ago on the island of Minorca (located in the Mediterranean Sea). A giant bunny might seem freaky but islands tend to do weird things to the size of animals. Small creatures now free of predation tend to balloon up into dodo birds and giant rats. Large animals, on the other hand, are constricted by the lack of food and shrink. Dwarf elephants shrank down to less than six feet tall. This insular dwarfism even effected humans. A brief offshoot of our genetic family tree was Homo floresiensis, affectionally known as the hobbit. They stood no taller than about a meter (3′ 6″).

I could go on, but books have literally been written on the subject. For now, I’ll depart, but the next time you want to see some biological quirks for yourself, look for the nearest island.

 

Virgin Births

It is not unusual for offspring to come from a single parent organism. This is the preferred method for the vast majority of living organisms. Simple, efficient, safe, and guarantee’d no worries about your partner’s current disposition. Nice. But among our close vertebrate phylum, asexual reproduction (known as parthenogenesis for us) is a bit of an oddity. However, it has been seen before.

Most recently, the BBC did a short segment on virgin births in sharks. It’s not unusual, although the fact that the most recent virgin mother just keeps doing it is cause for interest, since these are supposed to be rare events. A number of different lizards can produce parthenogenic offspring too, including the giant komodo dragon. In both of these cases the asexual reproduction is theorized to put the species at an advantage during tough times. The moms (who can only bear daughters) could theoretically rebound the population from seemingly unsustainable numbers.

Among birds and mammals, however, parthenogenesis is almost completely unknown. Although that is not to say that there haven’t been stories. In 1188 AD, Gerald of Wales wrote that geese could produce fatherless offspring in the Topographia Hiberniae.

There are here many birds that are called “Barnacles” [barnacoe] which in a wonderful way Nature unnaturally produces; they are like wild geese but smaller.  For they are born at first like pieces of gum on logs of timber washed by the waves.   Then enclosed in shells of a free form they hang by their beaks as if from the moss clinging to the wood and so at length in process of time obtaining a sure covering of feathers, they either dive off into the waters or fly away into free air. . .

I have myself seen many times with my own eyes more than a thousand minute corpuscles of this kind of bird hanging to one log on the shore of the sea, enclosed in shells and already formed. . . . Wherefore in certain parts of Ireland bishops and religious men in times of fast are used to eat these birds as not flesh nor being born of the flesh. . .

Like the Vegetable Lamb of Tartary, the geese seemed miraculous in origin and more plant-like than animal. Some apparently tried to use this anecdote to convince Jews of the virgin birth of Christ, along with also justifying the consumption of gooseflesh during Lent. However, in 1215 Pope Innocent III ruled that, fatherless or not, geese were geese and off limits.

Mammals are trickier. We have actually seen parthenogenesis in rabbits and mice, but only under heavy experimentation and developmental complications seem to arise in lab studies. In the early 2000’s a Korean scientist named Hoo Suk Wang proclaimed that he had discovered a method of inducing parthenogenesis in humans but was quickly discredited and ousted from the scientific community when it turned out he was a fraud and embezzler.

If Hoo Suk Wang had been telling the truth this might have proven to be a groundshaking development in developmental studies and reproductive technology. However, it seems that, for now, virgin births in humans will simply remain a facet of religion, not science.

Sources: BBC, Fordham.edu, Scientific American, Wikipedia

 

Lost Troop of Romans found in China

In 53 BC, the Roman General Marcus Crassus suffered a sound defeat at the hands of the Parthians, a nation that sat in what is present day Iran. He was captured, kept, and ultimately beheaded while his troops were scattered to the wind, effectively halting Roman advances Eastwards. No Parthian records were kept about the fate of his troops. They were written off as a lost legion, most likely killed by the local people or environment. Perhaps they made their way back westward, towards home.

However, evidence from a small village in China may prove that a few of them could have taken a quite more remarkable journey. During the time China too was a great empire, although contact with Rome was sparse and mostly consisted of indirect trade, and it too was focused on expansion. In 36 BC the Han found a group of mercenary soldiers were fighting for the Huns. There were about a hundred and fifty of them and they fought in what was described as a “fish-scale formation”. This would have been similar to a phalanx-like maneuver used by the Roman legions to protect their heads and flanks. The troops were released later to continue their wanderings.

Which leads us to the village of Liqian, China. The villagers here look quite different from the major Han ethnicity. They are often tall, not short, have green eyes, instead of brown, and blond or ruddy hair, not black. The villagers have long suspected that they may be descended from the Roman troop. To this end genetic testing was performed. Indeed, over half of the population did have Caucasian ancestry.

The scientists have been quick to caution against overenthusiastic conclusions. There are a great many other possibilities. However, the villagers have embraced these results as proof. And indeed, it would be a remarkable story to tell if it is true. The legion would have crossed thousands of miles of hostile terrain, some of the most mountainous terrain on the planet, and ended up surviving and thriving in what would have been to them an alien empire.

Source: The Telegraph, Wikipedia

 

Chickenosaurus

In his TED talk, Jack Horner says that he had two dreams as a child. One, to become a paleontologist. Two, to have a pet dinosaur. Well, today Mr. Horner is one of the most respected men in the field of paleontology. He discovered the first dinosaur eggs in the western hemisphere, pioneered the idea of dinosaurs as social animals, and personally advised Michael Crichton on the set of Jurassic Park (Horner even gets credit as part of the inspiration for Alan Grant). So Horner achieved his first dream admirably. The second? Not so much.

Alan Grant, on the other hand, has many dinosaur friends

But now that may change. Together with the McGill University geneticist Hans Larsson, Dr. Horner is attempting to retro-engineer a dinosaur into existence. Their plan is to activate or deactivate regulatory genes in modern chickens to produce teeth, arms, and a tail.

This is possible because birds are, technically, dinosaurs. Or at least the descendents of dinosaurs. As modern birds evolved ancestral dinosaur-like traits were covered up by genes turning off or changing, going missing, or being overwritten by different ones. Some of these are irrecoverably lost. However others are still present, just hidden. If we can find them, we can turn them on again. Horner’s team has already found the gene responsible for tooth growth and are now able to produce hen’s teeth on demand. They’re now working on the tail.

Of course, there are many questions about the direction of this project. Many religious groups see Horner’s actions as playing God. Others see it as a gimmick, the ultimate designer pet. Horner’s team says they are focused on furthering genetics and developmental biology as well as providing tangible proof of the bird-dinosaur evolutionary pathway.

The ultimate success of Horner’s work is yet to be seen, but I will be watching with interest. His personal thoughts, methods, and ideas are detailed in his book How to Build a DInosaur.

Sources: TED, CNN, Softpedia, crosswalk.com, Allmoviephoto, Amazon, and, of course, our good friend Wikipedia.

 

Gregor Mendel’s Luck

Gregor Mendel

Gregor Mendel was a nineteenth century monk widely known for his work with peas and genetics. It was his work in the abbey gardens that lead to the rules for simple inheritance. The Law of Segregation states that when an organism is producing sex cells (eggs and sperm) each cell gets one and only one copy of the genes. The Law of Independent Assortment states that each pair of genes divides independently of other genes. What copy or allele of gene A you get has no effect on which copy of gene B.

And although his work was lost for many years before being rediscovered in the twentieth century and later fused with Darwin’s ideas of natural selection, Mendel’s work sets him apart as a giant upon whose shoulders we have built our knowledge of biology.

However, the funny thing is, Mendel got pretty lucky.

Firstly, the Law of Segregation assumes that each organism only has two copies of a gene. And for the majority of plants and animals this is correct. However, there are exceptions. The peas he worked with do, in fact, have 2 sets of chromosomes (this is known as being diploid, or a 2N organism). However, other nearby plants were not. Apples can have an odd number of chromosomes (3N). Tobacco is a tetraploid (4N). Domestic oats are hexaploid (6N). Strawberries may have as many as eight copies of their chromosomes! It was quite fortunate that Mendel didn’t turn his attention to these plants since their crosses can get more complicated.

Freaks

Secondly, we now know that the Law of Independent assortment is not an absolute rule. When Mendel was working he assumed that each gene was free-floating and totally free from any other gene. This is not correct. Genes are tied together through their sequences into large collections of proteins and DNA known as chromosomes. And while chromosomes can switch around their genes with neighboring sister chromosomes during sperm or egg development, genes that are too close can affect each other’s chances.

Mendel worked with seven visible traits when he looked at peas. Each one just happened to be on a different chromosome and free from any possible interference. It would have been terribly easy for him to choose a trait that would not have been so easily understood. One of his laws may have never even gotten off of the ground.

Mendel was, overall, correct in his observations and the creation of his laws. However, it is quite amusing to sit back and consider just how lucky he was.

Sources: RNC, Wikimedia