All posts by Shweta Ramdas

Beginning life as a grad student studying human genetics.

Encoding Literature in DNA

In a couple of decades from now, your version of the Bible or Harry Potter (or the best-selling book of the 22nd century, whatever that might be) might just be stored in a small vial of liquid or on small chips. Harvard University researchers have just encoded a book in DNA fragments instead of on physical copy or e-copy.

The Alphabets of DNA

DNA is made up of building blocks called nucleotides, similar to how the English alphabet is made up of building blocks called alphabets. In the language of DNA, there are just 4 alphabets instead of 26, ‘A’, ‘T’, ‘G’ and ‘C’. Moving to information theory, each letter in DNA can thus encode 2 bits of information. Each nucleotide weighs around 250 Dalton (each Dalton weighs 1.66×10-24g). Thus, a single gram of single-stranded DNA could encode 455 exabytes (1 exabyte is 1018 bytes) of information. The previous sentence says ‘single-stranded’ because in nature, DNA molecules form two strands that wrap around each other to form a helix. Even keeping in mind this condition, a single gram of double stranded DNA could still encode around 225 exabytes, not a small number!

The four building blocks of DNA, also called bases (shown in green, red, yellow and blue) can be used as effective storage devices. [Image Credit: restlessmindboosters]

Translating English into DNAese

Encoding a book in DNA essentially means translating English into a code in a language of 4 letters. An html-encoded book called ‘Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves’ containing 53,426 words, 11 JPG images and a Javascript program has not been translated into the language of DNA. While DNA-encoding has been done on smaller scales before, the increasing ease and decreasing cost of DNA sequencing has made it possible to encode larger quantities of text in this biological molecule.

The entire book was translated onto small fragments of DNA called oligonucleotides. Each of these fragments had information from the book, and a small block with information for the ‘address’, where in the book the block belonged to. Thus, a ‘library’ of oligonucleotides is created on a DNA microchip. To ‘read’ the book, this library has to be amplified and sequenced using molecular approaches. These researchers encoded just one bit of information per DNA base instead of the maximum two, made multiple copies of the same oligonucleotide fragment so that errors could be accounted for, and still obtained a whopping density of 5.5 petabits (1015 bits) per millimeter cube.

Current costs of sequencing make this technology prohibitive.  However, the costs of DNA synthesis and sequencing are decreasing exponentially every year, making this a feasible storage molecule for the future. DNA is also stable at room temperature meaning it can be preserved for long periods. While DNA storage and retrieval is slower compared to other methods, its scale offers huge potential. It could thus be used in applications involving archival storage of massive amounts of data.

You can read more about this research here.

Brain’s Drainage System Discovered

Our body comes with an inbuilt drainage system called the lymphatic system. The tissues in our body lie in a pool of fluid called the interstitial fluid. While most of this fluid is directly circulated and recirculated from and into the blood vessels (called the body’s circulatory system), about 1% of this fluid is re-circulated through a different route. Interstitial fluid enters a network of vessels called lymph vessels, which in turn drain excess proteins and waste material from this fluid and into larger blood vessels for recirculation or destruction. The lymphatic system is thus an accessory system that acts in parallel with the blood circulatory system to remove excess proteins and solutes from tissues.

Fluid Flow in the Brain

Apart from blood vessels, the brain also has a fluid called the cerebrospinal fluid (CSF) circulating in its outer parts. This fluid maintains brain pressure and protects the brain from physical injury. However, a system analogous to the body’s lymphatic system has not been seen in the brain till date. This is surprising because the brain has a very high metabolic rate and brain cells are particularly sensitive to the balance of chemicals in their environment. So how does brain tissue drain waste? It has been speculated that the CSF could perform the drainage role in the brain.

Injecting Fluorescent Molecules into the Brain

How does waste from the brain tissue get out of the brain? If it is through the CSF, then the question becomes—how do tissues release their waste into the CSF which has so far been found only in the sub-arachnoid space, the outer areas of the brain? Researchers from the University of Rochester injected small amounts of fluorescent ‘tracer ‘molecules into the brain’s CSF, and as the name suggests, traced the destinations of these tracers by brain scans. They found new channels through which the CSF flows, right into the brain tissue, called brain parenchyma. They could trace the paths of these molecules, and using molecules of different sizes, they could estimate the volumes of these paths through the brain.

The thick vessel is an artery in the brain of a mouse. In green is cerebrospinal fluid in a channel along the outside of the artery. [Image Credit: University of Rochester medical Center]
They found that the CSF traverses the inner parts of the brain including the space around brain tissue in hitherto unknown channels that lie parallel to and on the boundaries of the brain’s arteries and veins, formed by cells called astrocytes. Moreover, when a water-transport gene called AQP4 was deleted in mice, fluid flow through this system was suppressed, meaning that water-transport helps build up the pressure to move things along in this system using bulk-flow or convection. The water-pressure creates a pressure allowing waste to be drained away faster. The brain’s lymphatic system has thus been found, and is being referred to as the ‘glymphatic system’, called so because cells called glial cells help create pressure.

Alzheimer’s Molecule Takes This Route

The researchers went one step further and traced the path of fluorescent-tagged amyloid b, the protein responsible for Alzheimer’s disease. They found that this protein travels along this route of ‘glymphatic’ blood vessels. This insight provides therapeutic possibilities. Improving flow through this system could speed up clearance of neurodegradative molecules like amyloid-beta from the brain. Conversely, impeding or reducing flow through this system might help retain vaccines or drugs in the brain tissue for a longer period of time. If these vessels are also routes for migrating cells, could the metastasis of cancerous tumour cells be dependent on this system too?

“Waste clearance is of central importance to every organ, and there have been long-standing questions about how the brain gets rid of its waste,” said Maiken Nedergaard, M.D., D.M.Sc., lead author of the paper and co-director at the University of Rochester’s Center for Translational Neuromedicine. “This work shows that the brain is cleansing itself in a more organized way and on a much larger scale than has been realized previously.You can read about this research here and here.

Of Mice that Sing

A movie called ‘Ratatouille’ showed us a cartoon mouse that could cook up wonders. The real world matches this with mice that don’t just squeak, but sing too.

Singing for the Women

Scotinomys teguina are mice from the mountains of Costa Rica which communicate by singing. Before you start preparing to teach your next non-avian pet the latest from Adele, the singing capacity of these marvelous creatures is restricted to trilling—a rapid alternation between two adjacent notes. In several species of birds, males with greater trill production are seen to be greater threats by rivals, and seen as more attractive by females. Likewise, the male singing mouse emits a series of rapid high-pitched chirps to attract mates and fend off rivals.

Researchers at the University of Texas are now studying these mice to try and understand the genes that lead to this singing behavior—genes which could in turn regulate language in humans. It is known that music and language are processed by the same brain systems in humans in a part of the brain called the temporal lobes.

Looking for a ‘Singing Gene’

It is one gene in particular that is being studied, a gene called FOXP2 (Forkhead Box Protein P2). This gene is highly conserved across humans, singing mice and lab mice. In humans, mutations of this gene has been found to lead to speech and language disorders. In birds, removing this gene leads to inaccurate song imitation. The research team is sequencing this entire gene in the singing mice and looking for segments of DNA that are present only in the singing mouse as opposed to the lab mouse; from this set of changes, the team then filters out those that are likely to have occurred by chance and have no biological significance. The remaining gene changes are those that could be responsible for the ability of the singing mice to trill.

Another way to study this single gene is to look at its function. This protein regulates the expression and activities of a host of other proteins—what are they? “We found that when an animal hears a song from the same species, these neurons that carry FOXP2 become activated. So we think that FOXP2 may play a role in integrating that information,” said Lauren O’Connell, a researcher in Steven Phelps’s lab, where this research is being conducted. They are now making the mice listen to songs, and record all the genes that are activated, to see which ones could be activated by FOXP2. This information will help us form the complete link between the gene and the biological property of singing or language in humans.

You can learn more about this research here.

Fossils Point to Multiple ‘Homo’ Species

Fossil Questions if Our Ancestors Had Cousins

There exists a fossil of a human skull, labelled 1470, which has been at the center of quite a bit of controversy since its discovery in 1972. This fossil, said to be from 2 million years ago, was different enough from the existing human ancestor at that period—Homo erectus—for some scientists to propose that it belonged to a new species. And thus were formed two warring camps. One said that 1470 belonged to Homo erectus, and the difference could be accounted for by variation within a species. The other camp believed that 1470 represented a remnant of a new species that might have existed along with Homo erectus, meaning that the lineage of current humans might not be as linear as we think it is.

A timeline in Homo sapiens evolution. Homo rudolfensis is the contested species which might have co-existed with two others.
A timeline in Homo sapiens evolution. Homo rudolfensis is the contested species which might have co-existed with two others. [Image Credit: Nature]

Now, the discovery of three new fossils has strengthened the claims of the second camp. These were discovered by a team led by Meave Leakey (who was also involved in discovering 1470) also near Lake Turkana in Kenya. The new fossils, which are from 1.78 to .95 million years ago, resemble fossil 1470 in skull structure by having similarly large and flat faces. Scientists are saying that the presence of more than a single outlier suggests that 1470 wasn’t just an unusual case in the species Homo erectus, but just one among a number of individuals in an altogether new species, which they are calling Homo rudolfensis. This finding contradicts the belief that our species evolved from the ancestors we share with apes in a strictly linear progression. The authors of this research believe that 3 species existed simultaneously—erectus, 1470 and a third branch— of which erectus eventually evolved to become Homo sapiens.

Not Definitive Evidence

This discovery isn’t convincing the critics, though, who think the evidence is not definite, and that the three fossils could still be diverse members of the same species. For now, our family tree remains murky.

You can unearth more information about this research here and here.

New Bird on The Block

All you bird-lovers, it’s time to say hello to a new species in the bird kingdom that has just been discovered. Capito fitzpatricki, discovered in the mountains of Peru, is the latest ‘official’ bird. It has been named after Dr. John Fitzpatrick, director of the Cornell Lab of Ornithology, who himself has previously been involved in the discovery of six bird species.

The Andes in South America is a region with an unrivaled rate of new species discovery; however, a thorough exploration of these regions is hindered by the difficult terrain. In 2008, a group of researchers undertook an expedition to a region of the mountains called the “Cerros del Sira” and chanced upon this colourful bird, also called the ‘Sira barbet’ in a flock consisting of birds of multiple species. After 6 days of exploration in nearby regions, they found more samples of this bird.

Behold the newest bird known to mankind [Image credit: Cornell University]
Behold the newest bird known to mankind [Image credit: Cornell University]

Capito fitzpatrickibelongs to the group of birds called barbets. These are tropical, frugivorous (fruit-eating) birds characterized by big heads and bristles below their bills. They are greenish or brown with splashes of bright colours or white and are found in South and Central America, Sub-Saharan Africa and South-East Asia.

How can we be sure Capito fitzpatricki belongs to a different species and is not merely a distant cousin of an existing barbet species? Firstly, it has different plumage characteristics—it has different colourings on its thigh and lower back. Secondly, the DNA sequences of this species were compared with other species in the genera Capito. The divergence, or dissimilarity, in mitochondrial DNA sequence from fitzpatricki and its closest ‘genetic neighbour’ Capito wallacei was in general greater than the divergence seen between two species.

The discovery was published here.

 

How Your Sex Affects How You Age

Women are known to live 5 to 10 years longer than men. One of the reasons for this asymmetry has been revealed.

How We Get Our DNA

It is fairly common knowledge that we inherit half our DNA paternally and the other half maternally. There is actually a correction to that — we inherit half of what is called nuclear DNA from our fathers and the other half from our mothers.

Mom, Give Me My Mitochondria!

The DNA that encodes for most of the genes in our body exists in a compartment of the cell called the nucleus. Almost all the diverse functions in our body in some way lead from the sequence of this DNA. Almost all, but respiration. Respiratory genes of our body lie in another compartment of the cell called the mitochondria. The mitochondria comes with its own set of DNA, and this set is inherited directly from the mother. This is because of the mechanism of fertilization. It is only the nucleus of the sperm that fuses with the mother’s egg cell to produce the first baby cell (also called a zygote).

The lifespan of males is 5-10 years lower than that of females. Our mitochondria could hold the key to this number. [Image Credit: Wikipedia]

How Are We Protected From Mutations?

Moving on to mutations, evolution selects against a mutation in a gene if it is harmful to the organism. A little simplistically, if a mutation in a gene affects the mother or the father, then it will have less chances of being passed on to the next generation. An extreme example of this would be if an individual has a mutation that causes individuals to die young. Since people with these mutations would reproduce less, it would never be allowed to become widespread in the population.
When you bring mitochondrial genes into the mix, you get something interesting. Mutations in the mitochondrial DNA that affect only males have no harmful effects in mothers. Thus, a woman with such mitochondrial mutations would simply pass on such mutations without any “weeding” taking place. Over generations, you could see an accumulations of such mutations which would affect males, but they would have no selection pressure on them because of their transmission through females only.

Fruit Flies Show Anti-Male Mutations in Mitochondria

This is exactly what researchers have found in fruit flies. They compared 13 populations of fruit flies with identical nuclear DNA but different mitochondrial DNA. After growing them in identical conditions, they computed longevity of these populations and found that female flies lived longer (on average, they lived 11 days longer than male flies— a significant difference in the fly life span!). Thus, sex-specific patterns of aging are because the mitochondrial DNA have mutations that affect some component of aging in males, but are either neutral or beneficial in females. Mitochondrial genes are often linked to aging, because respiration leads to the production of toxic substances that can damage our DNA. Respiration is ‘oxidising’, that’s why we hear so much about using anti-oxidants to prevent aging.

This points to a sex-specific sieve that could contribute to differences in life spans between the two sexes. You can read about this research here.

Search For Extra-terrestrial Life Just Got Harder

It’s not just our bodies that have left-handedness and right-handedness. It has long been known that molecules within living organisms also possess the property of asymmetry, also called chirality. This simply means that a molecule does not match its mirror image. Thus, while the proteins in our body are composed of amino acids that are left-handed, the sugars are right-handed.

The Importance of Handedness in Life

This preponderance in one type of handedness has long been considered as essential property and prerequisite of ‘life’ itself. This is mainly because inorganic substances contain roughly equal quantities of both left-handed and right-handed molecules. Thus the question of why only molecules with one type of ‘handedness’ would arise in living organisms from a nearly equal distribution of molecules continues to be important in studying the origins of life.

This intrinsic asymmetry is actually being used by space missions, like the ExoMars mission, as an elegant way of detecting traces of life in outer space.

The Tagish Lake Meteorite, which showed an excess of 'L' aspartic acid, an amino acid. [Image Credit: wikipedia]
The Tagish Lake Meteorite, which showed an excess of  ‘L’ aspartic acid, an amino acid. [Image Credit: wikipedia]
Meteorites found at Taglish lake in Canada, have however shown results that bring this hypothesis to a screeching halt. Researchers have analysed these meteorites for proportions of left- handed ‘L’ and right-handed ‘R’ amino acids, and found an excess of ‘L’ types for some of them.

Meteors as Remnants of a Pre-Life Universe

Meteors represent parts of the extra-terrestrial universe before the emergence of life. Amino acids in these meteors were confirmed to be extra-terrestrial in origin by studying their carbon isotopes. Researchers are proposing that heating in the early days of the solar system melted ice to produce water which dissolved existing amino acids into populations of chiral asymmetric molecules. The amino acids which were found to be excessively present in one form are susceptible to forming asymmetric populations depending on the chirality of the starting amino acid. Thus, a small quantity of an asymmetric molecule could have set off a cascade leading to a highly asymmetric group of amino acids.

“As evidence mounts that [left-handed] excess occurs naturally across bodies in the solar system, any strategies designed to search for life based on looking for this excess require serious rethinking,” saysAlberto Fairen of the SETI Institute in Mountain View, California.

This does NOT, however, in any way, disprove the existence of extraterrestrial life. Chirality is just one aspect of life, and the search of life in outer space will continue.

You can read about this research here and here.

Have Excellent Autobiographical Memory? Your Brain is Differently Wired.

Do you remember what happened on the 6th June, 1999? Or 19 September 2000? Well, if you can effortlessly reel off the answers, and in general recollect events in your life with remarkable accuracy, you don’t just have good memory—you’d be pleased to know that you have what is called “Highly Superior Autobiographical Memory”.

This is a newly described ability of individuals to recall events from their personal past, including the days and dates of occurrence, with high accuracy. People with strong memories don’t necessarily have HSAM. They use certain mnemonics and strategies to perfect the art of memory, and this often doesn’t extend to autobiographical memories. In a case of one of the most famous mnemonists, the patient described living his life “in a haze”. Conversely, intense rehearsal of memories does not seem to be the primary means by which people with HSAM store their rich repertoire of memories.

Having excellent autobiographical memory could be a result of your brain being structured differently. [Image Credit: flickr.com/digitalshotgun]
Having excellent autobiographical memory could be a result of your brain being structured differently. [Image Credit: flickr.com/digitalshotgun]

How Are they “Highly Superior”?

Researchers at the University of California, Irvine tried to see if this difference between high autobiographical memory and good memory was also reflected in the way these are stored in the brain. They recruited people who claimed to have extremely good autobiographical memories and performed routine memorization tests on them. They identified 11 people who had vastly superior abilities to remember events in their past. However, these people performed no better than normal individuals on these tests. Yet when it came to public or private events that occurred after age 10½, “they were remarkably better at recalling the details of their lives,” said McGaugh, senior author on the new work.

They found that HSAM participants also had obsessive tendencies, though it remains unclear if the two are linked, and if so, how. Furthermore, they found that the brains of these participants were anatomically different from the brains of normal participants in 9 structures. Using MRI, some of these regions are shown to be active while autobiographical memories are being recalled.

Cause or Effect?

It must be noted, however, that these structural differences could either be a cause of HSAM or an effect. Our brains are remarkably plastic and embody the saying ‘we are what we do’. The wiring of our brains is subject to change upon repeated patterns of activity. Thus, the difference in certain brain regions of people with HSAM could simply arise as a result of different thought patterns in these people. Either way, this research does give us more information about the intricate workings of the brain and how it resolves the details of the world we live in.

You can read about this work here. It was published in the journal Neuroscience.

 

Discovered: New Solar System that Looks Like Ours

Our solar system now has a cousin! Astrophysicists at the MIT have discovered another planetary system that resembles ours. This system is around 10000 light years away from earth.

How do you define ‘similar’? Does that mean the presence of an Earth with life? Well, not quite. Our solar system has the unique property that the orbits of its planets are nearly perfectly aligned in a plane, like lanes on a track field. This is quite in contrast with most exoplanetary systems, some of which have quite eccentric orbits. For the first time, another planetary system with perfectly aligned orbits has been discovered.

A cartoon depicting the coplanar orbits of our solar system. [Image Credit: universetoday, NASA/JPL-Caltech/T.Pyle]

Pointing Telescopes at a Star Called Kepler-30

Researchers at MIT trained their telescopes—one particular telescope, in fact, called the Kepler Telescope—on a star called Kepler-30. This star has three planets. Because the star is so far away, the only way to study it is to measure the small amount of light it radiates. They tried to determine the orbits of these planets by observing decreases in light intensity from this planet and its sunspots, which would occur when a planet transited across the observed face of the star. These sunspots themselves are moving with respect to the earth because of the star’s rotation about its axis. Thus, every time a planet transits across the star, it blocks a sunspot at a different position.

Using the timing of this data, the orbits of the 3 planets could be determined, and they were found to lie on a plane, exactly like the solar system. The orbits of the planets were also in a plane perpendicular to the star’s axis of rotation. These results were published in the journal Nature.

It’s telling me that the solar system isn’t some fluke,” says Josh Winn, an associate professor of physics at MIT and a co-author. “The fact that the sun’s rotation is lined up with the planets’ orbits, that’s probably not some freak coincidence.”

How were Systems with Non-Coplanar Orbits Formed?

This finding also backs theories on system of other planets called ‘hot Jupiters’. These are large planets with misaligned orbits around their stars. It is hypothesized that ‘planetary scattering’ led to their misaligned orbits. This theory says that these stars came close to other giant stars in the early stages of planetary system formation, and threw some planets out of the system while bringing others closer to their stars. The existence of another non-hot Jupiter system with planets far away from each other gives further credence to this hypothesis.

“We’ve been hungry for one like this, where it’s not exactly like the solar system, but at least it’s more normal, where the planets and the star are aligned with each other,” Winn says. “It’s the first case where we can say that, besides the solar system.” You can read about this research here.

How does the Brain Distinguish Between Old and New? It is Biased.

Last weekend, I went to a cinema in the USA for the first time. I was conscious of two things—taking in the cine-going experience in a new country, and reminiscing about the last time I was at a theatre with my friends a year ago.

Is This Memory Already Stored Inside Me?

When we come across a situation, there are two conflicting processes that can take place- a new memory can be formed, or an old memory can be retrieved. Both these processes involve a common region of the brain called the hippocampus. However, despite the effortlessness with which we form memories and simultaneously recall old ones, the two processes themselves involve very different networks. Recalling a memory involves maximizing overlap with existing memories. On the contrary, forming a new memory involves minimizing the overlap with other memories. These are two conflicting requirements; how, then, does the brain decide what to do?

Recent experiments by researchers at Columbia University and New York University are showing that this decision is influenced by incidents prior to the decision. That is, prior incidents bias our brain either towards forming a new memory or towards recalling an existing one.

The brain is not very objective in its decision making. [Image Credit: Wikimedia Commons]
Participants were presented with pictures of novel and familiar objects and asked to classify them into one of three classes— identical, different, or similar but not identical to a previously encountered object. The ‘test’ objects were very similar to previous objects, but had subtle differences. It was found that participants who had been primed with a series of new objects tended to classify these as not identical, whereas participants who had been primed with familiar objects tended to classify them as identical. In another experiment, participants were found to form links between overlapping memories better if these overlapping memories had been formed after a retrieval of a memory, and their ability to form links between memories was less if the memories had been formed after a new memory had been formed. That is, a preceding experience definitely affects how a memory is stored in the brain with respect to other memories.

Biased by Our Environment

“We’ve all had the experience of seeing an unexpected familiar face as we walk down the street and much work has been done to understand how it is that we can come to recognize these unexpected events,” said Lila Davachi, an associate professor in NYU’s Department of Psychology and the study’s senior author. “However, what has never been appreciated is that simply seeing that face can have a substantial impact on your future state of mind and can allow you, for example, to notice the new café that just opened on the corner or the new flowers in the garden down the street.”
This is behavioral evidence that memory encoding and retrieval can evoke biases which influence subsequent memory processing. The production of this bias may be an adaptive mechanism. Making the decision about retrieval or creation of memory uses up resources, and it is very rarely that our experiences rapidly switch between the familiar and the novel. It could thus be advantageous for our nervous system to be more receptive to change in new environments and less sensitive to irregularities in familiar environments.
You can read more about this research here.