Tag Archives: chromosome

Credit: Camilo Medina for Mosaic.

You won’t believe these three unexpected discoveries – and neither did the scientists who made them

Science, mostly, progresses iteratively. But every now and then, a discovery will be made – often incidental to the main aim of the research – that is entirely unexpected. Such serendipitous findings enable us to leapfrog our usual incremental advances. They can even disrupt a whole field of research.

In 2003, the Human Genome Project, the 13-year-long international effort to fully sequence human DNA and identify all our genes, was completed. The Wellcome Sanger Institute, near Cambridge, England, was the only British organisation involved, completing the sequence of one-third of the genome.

While many of the great proclamations made at the launch of the project have yet to be realised, there is no doubt that sequencing the human genome was a technological game-changer for science in the way that, say, the invention of the printing press and microscopes were in previous centuries. And, just as for other disrupting technologies, genome sequencing has led to some wholly unexpected findings.


1. Chromosome shattering can cause cancer

Credit: Camilo Medina for Mosaic.

Credit: Camilo Medina for Mosaic.

Cancer is a genetic disease. Through replication errors and mutations in DNA, healthy cells form tumours that can kill us. Today, researchers are sequencing the genomes of many tumours and through this transforming our understanding of what exactly cancer is.

Peter Campbell, who heads Sanger’s cancer programme, has made a few unexpected discoveries in his work with kidney tumours, but the most remarkable was an entirely new cancer-triggering mechanism.

He and his colleagues found that a chromosome can explode for unknown reasons, shattering into hundreds of pieces.

It was such a surprising finding that Campbell assumed it was because of a problem with the data. “Almost all of these things turn out to be rubbish in the data – someone’s mucked something up somewhere along the line. So usually it starts with us saying: we need to figure out what’s gone wrong,” he says. However, no obvious error could be found.

“The advantage of working with genetic data is it’s black and white, it behaves in a digital way – unlike, say, cells, which can look different on different days.”

Once he’d confirmed the discovery, Campbell allowed himself to get excited. Science, he notes, is usually a very long-term project: “You can be banging your head against problems that you can’t solve for weeks on end… then unexpected findings drop out all of a sudden.”

Campbell prepared himself for a backlash from the field. In the end, though, his research paper was received very positively, and others have since confirmed his findings, capturing the changes occurring in cells grown in the laboratory. The mechanism is likely to trigger many different cancers, researchers believe.

So has the finding shifted people’s thinking? “Yeah, I think so,” says Peter. “The best papers do that, but they come along not so often in one’s own career. We were lucky that we had very early access to the modern genetic technologies that allowed us to spot these patterns before others did.”


2. The Y chromosome is not useless after all

Credit: Camilo Medina for Mosaic.

Credit: Camilo Medina for Mosaic.

Haematologist George Vassiliou and his team were looking for new targets for drugs to treat leukaemia. One such target was a cancer-suppressing gene called UTX, which sits on the X chromosome.

As part of their investigations, they were using mice with faulty versions of the UTX gene to see when they got cancer. During these experiments, Vassiliou also tweaked a similar non-functional gene on the Y chromosome called UTY.

Aside from the gene that determines sex, Y chromosome genes were largely thought to be non-functional leftovers. In fact, the mole vole has evolved to lose its Y chromosome altogether.

Researchers have suggested that the same could happen in humans eventually. That was until Vassiliou’s team discovered that the UTY gene is functional in humans. What’s more, they found that it plays a significant role in suppressing cancer.

“It was very exciting,” he says. “At first, we were so happy to find another potential target for leukaemia treatment.”

But then there was a moment of realisation: “The Y chromosome actually does something! It is not useless after all.”


3. Bacterial genes we thought might not do anything actually affect how well vaccines work

Credit: Camilo Medina for Mosaic.

Credit: Camilo Medina for Mosaic.

Jukka Corander, a biostatistician at the Sanger Institute and University of Oslo, and Nicholas Croucher, a bacterial geneticist at Imperial College London, were exploring the genomics of bacterial infections. They used computer simulations of multiple strains to figure out what causes bacterial populations to change in unexpected ways after vaccination against them.

They were comparing the genomes of Streptococcus pneumoniae, a bacterium that causes severe illnesses such as pneumonia, sepsis and meningitis. This involved collections of bacteria from four different human populations around the world, three of which had been vaccinated against the bacterium.

All Streptococcus pneumoniae strains have around 2,000 genes. Three-quarters of these genes are very similar across strains. The remaining ‘accessory genes’ vary considerably between them. Bacterial strains can swap any gene through a process called horizontal gene transfer.

The modelling showed that the levels of accessory genes were very similar in the bacterial population before and after vaccination, even though the types of strain present had changed dramatically.

In other words, the strains that emerged after vaccination had similar sets of accessory genes to the strains eliminated by vaccination. So – far from being useless – accessory genes appear to play a role in how the bacterial population responds to a vaccine.

Importantly, some of the accessory genes that returned to their previous levels are involved in resistance to antibiotics.

“We had just published a paper that agreed with the ‘neutral model’ of the accessory genes,” Corander says, “so I was utterly astonished.”

This work provides the foundation for further research that will help predict which strains will spread most rapidly after a change to how we treat bacterial diseases.

“Without having access to high-definition genomes, we would never have seen this,” Corander says. “We wouldn’t even have known that so much variation exists in the genomes, let alone this important role of these rare accessory genes.”

Wellcome, the publisher of Mosaic, founded the Wellcome Sanger Institute in 1993 and has funded it ever since. The Sanger Institute celebrates its 25th anniversary in October 2018.

Nicholas Croucher holds a Sir Henry Dale Fellowship, which is funded by Wellcome and the Royal Society. Peter Campbell receives funding from Wellcome through a Senior Research Fellowship in Clinical Science.

This article was written by Gaia Vince and first appeared on Mosaic and is republished here under a Creative Commons licence.


Wheat’s genetic secrets could lead to better, more resilient crops

Wheat has a genome five times longer than yours — and now, it’s been fully sequenced.


Image credits Brad Higham / Flickr.

Staying true to their name, researchers at the International Wheat Genome Sequencing Consortium have published a paper containing the complete sequence of the wheat (genus Triticum) genome, a dataset that could help breed new crops.


Having access to the plant’s genome should help speed up the breeding of more resilient, disease-resistant, and higher-yield crops. Wheat is currently the most widely grown crop, providing more protein than meat in the human diet, and supplying roughly one-fifth of the total calories people consume. It’s also surprisingly complex from a genetic standpoint: its genome includes some 16 million base pairs, over five times larger than yours or mine.

Despite its genetic beefiness, wheat is quite vulnerable to floods, droughts, and several diseases (such as wheat rust) that can claim whole crops at a time. Luckily, now that we know the structure of its genome, we can modify it to add a whole lot of desirable characteristics — resilience to pests, higher yields, more nutritional value — into our crops.

Actually sequencing the genome, however, proved to be a significant challenge. Not only was it huge, it also included three sub-genomes — a large part of which included repetitive elements. This makes long stretches of the genome identical or very similar to each other, making it difficult to distinguish individual chains and re-constructing the overall genome.

The sequencing effort is detailed in two papers. The first, published by researchers from the. International Wheat Genome Sequencing Consortium, details the sequence of the plant’s 21 chromosomes. It also lists the location of 107,891 genes, more than 4 million molecular markers, as well as sequence elements between the genes that regulate their expression.

The second paper, led by a team at the John Innes Centre (JIC), aims to help breeders and researchers understand what trait each gene affects. This work is largely based on a technique known as ‘speed breeding’, previously developed at the JIC. Speed breeding involves the use of glasshouses to shorten the breedings cycles of plants. Combined with the wealth of genome information from the first paper, this helped the team significantly shorten the time required to test what each gene does.

“Genomic knowledge of other crops has driven progress in selecting and breeding important traits,” says Cristobal Uauy, Project Leader in crop genetics at the John Innes Centre says.

“Tackling the colossal wheat genome has been a Herculean challenge, but completing this work means we can identify genes controlling traits of interest more rapidly. This will facilitate and make more effective the breeding for traits like drought or disease resistance. Where previously we had a broad view and could spot areas of interest, we can now zoom into the detail on the map.”

Uauy cites past research estimating that the world will need 60% more wheat by 2050 to meet global demand. The research his team performed can be instrumental towards reaching that goal.

It’s not the first time researchers have fully decoded the genome of a cereal: just last year, an international research team published the full genome of barley.

The first paper, “Shifting the limits in wheat research and breeding using a fully annotated reference genome”, has been published in the journal Science.

The second paper “The transcriptional landscape of polyploid wheat” has been published in the journal Science.

mitosis artsy.

What Are Five Stages of Mitosis?

mitosis artsy.

“Mitosis or Fusion?” artwork.
Image credits Mike Lewinski / Flickr.

Our bodies are collections of cells, all bunched up and working together to help you successfully navigate adult life. Being the ideal heap of cells, however, involves some growing and quite a lot of maintenance. If it sounds like hard work, it’s because it probably is. Luckily for us, cells have a secret ace up their sleeves: they can simply copy-paste themselves to create new, identical members. This process — called mitosis or, more colloquially, cell division — is what allows organisms to grow, develop, and heal with virtually no conscious effort.

I’m a huge fan of not making any conscious effort — so let’s all appreciate all the work our cells aren’t putting us through while we take a look at mitosis.

Readers be warned: we will be using the animal cell as a template to discuss the processes involved. There will be some differences here and there between how these and other types of cells handle mitosis.

What is mitosis?

Mitosis is one of two types of cellular division — the other being meiosis. They’re largely identical, with the key difference being that mitosis results in two daughter cells, each with the same number and type of chromosomes as their parent, while meiosis results in cells that only have half of the parent’s chromosomes. Mitosis is how regular cells — the ones that make up your tissues, your pet’s tissues, or the yeast that fermented your beer — multiply. Meiosis is how our bodies produce sex cells, like sperm and eggs.

While it goes on without us actually doing anything (beyond staying fed and not-dead, obviously), there’s a lot of work involved in mitosis. We’ve classified the steps of this process in ‘phases’ that each cell must go through before it can divide. These are, in order:



This isn’t strictly speaking part of the meiosis process; rather, it’s more of a default-state for cells. They spend most of their lifespan in interphase, performing their usual functions and getting all stocked up on nutrients. As baby-cell-making time swings around, i.e. the later stages of interphase, cells start duplicating their internal structures — they create two copies of their DNA and of each organelle.

Interphase is generally broken down in two to three separate sub-phases:

  • Growth (G1) phase, during which the cell doubles-down on synthesizing virtually its full array of proteins, especially the structural proteins it will need to grow.
  • Synthesis (S) phase: this is when the cell’s chromosomes are duplicated.
  • [In some cases] Growth (G2) phase, which is very similar in form and function to the G1.



This is when the cell starts going into reproduction mode proper. One of the first things that happen during prophase is that the cell’s (now double-helping of) DNA condenses into pairs of chromosomes. Think of it like archiving a folder on your computer — all the information is still there, only much more compact and easier to share with your kids.

Another important event is the formation of the mitotic spindle. This starts with the cell’s centrioles — the organelles that secrete these microtubules, made from the protein that forms the spindle and cellular support skeleton — moving to the poles. From there, they release microtubules, gradually pushing them towards the middle, where they’ll eventually fuse. The mitotic spindle will elongate the cell during prophase, which will come in handy during division.

Finally, the cell’s nucleolus — the largest structure inside the nucleus, which assembles ribosomes — disappears, setting the stage for the nucleus to break down.



During a brief time window called prometaphase (the “before metaphase”), the membrane around the chromosomes breaks down. This will release the chromosomes inside the cell, and they will affix to the mitotic spindle on the equatorial plane.

The spindle is there to ensure that each daughter cell will receive a full copy of the original’s DNA. It does this by pulling the chromosome pairs onto its filaments, right across the equatorial plane — an imaginary line that falls roughly along the cell’s midline. This sorts the genetic data, so to speak, ensuring that each of the new cells-to-be will get one chromosome from each pair before the cell divides. Not all microtubules stick to a chromosome — those that do are known as kinetochore microtubules. The other microtubules will span the cell and grab on to microtubules coming from the other side, to stabilize the spindle.


The mitotic spindle in a human cell showing microtubules in green, chromosomes (DNA) in blue, and kinetochores in red.

During metaphase proper, all chromosomes are drawn into place on the spindle across the equatorial plane. By this time, each chromosome’s kinetochore — a complex protein structure associated with the chromosomes that, among other things, contains a molecular motor — should be attached to microtubules from opposite spindle poles.

Eukaryotic cells go through a lot of effort to ensure genetic integrity during mitosis — else they risk their health and that of the organism. Before proceeding to the next phase, the cell has to pass the ‘spindle checkpoint’: if all chromosome pairs are on the equatorial plane, and properly aligned (one half toward each end of the spindle), the cell gives the green light. If not, it pauses the mitosis process until everything is set.



During anaphase, the ‘glue’ holding each chromosome pair together breaks down and their members get pulled to the opposite sides of the cell — by this point, each half of the mother cell harbors a complete copy of its DNA, and the actual division can begin.

The chromosomes are pulled by kinetochore microtubules, which start to shorten towards the opposing centromeres. At the same time, the structural microtubules grow, pushing at each other, elongating the cell; imagine stretching a piece of chewing gum between your fingers — that’s roughly the shape cells take during this phase. All this activity is powered by motor proteins, such as the one in the chromosomes’ kinetochores that pull them along microtubules.



By this point, the cell is nearly done dividing, hurray!

Since cells are really a tidy lot, the new daughter cells start re-forming their internal structures even while they’re still connected along the membrane. The mitotic spindle is the first structure to be broken down, its building blocks recycled into the new cells’ support skeletons. Each set of chromosomes comes together, and the nuclei form, fully-equipped with their own membranes and nucleoli.

Finally, the chromosomes begin to unpack, reforming into long strands of DNA in the nucleus.



Sometimes considered as the later part of telophase, this stage sees the division of cytoplasm (the gooey stuff inside cells) between the two daughters. Cytokinesis can actually start as early as during anaphase (most notably for certain plant cells) but always ends shortly after telophase.

In animal cells, the process of cytokinesis constricts their membranes where they meet — like a piece of string tied around a balloon. That string is a band of actin filaments. The goal of this contraction is to progressively pull the membranes into an ‘8’ shape, after which the cells pop free of each other.

Plant cells, which tend to reinforce their membranes with compounds such as cellulose and hemicellulose, don’t employ the same mechanism. Instead, they form a structure called a cell plate down their middle, splitting the two daughter cells with a new wall.

And voilà! Two new cells, identical to their parent, are now ready to mingle and toil for the collective good.


Despite all the checks and balances biology set in place to make sure mitosis goes through smoothly, sometimes it doesn’t. For cells, any errors that take place during mitosis can have significant effects. For us, multicellular organisms that we are, not so much — but it can still affect us.

One of the most abhorred outcomes of bad mitosis is cancer(link). Faulty copies or improper distribution of chromosomes during mitosis can induce genetic errors, which can cause mutations in daughter cells. Some mutations are silent (they don’t have an impact on the sequence’s role) but those that alter amino acid synthesis (called missense mutations) often have an impact on the cell’s workings. Over time, enough such mutations can add up, disrupting the cell’s normal activity, leading to the formation of tumors. Cancer occurs when mutated tumor cells override their natural limits and checks on mitosis, starting to reproduce uncontrollably.

Another way mitosis can go awry are chromosome abnormalities(link). In short, sometimes the chromosome pairs fail to attach to the spindle, and a daughter cell will end up with an extra or a missing chromosome after division (a condition known as aneuploidy). This error can have far-reaching effects on the body. For context, Down’s syndrome is caused by the presence of an extra chromosome in every cell — it arises from aneuploid sperm or eggs, so it’s a meiotic, not a mitotic error. Still, it illustrates what a body-wide difference of a single chromosome can do. Meiotic chromosomal abnormalities generally only affect one or a small number of cells, based on random mutation.

Cell mutations can also lead to mosaicism(link). This describes a condition in which some cells in the body have a mutant version of a gene, while others carry the normal version. In somatic cells (your body’s cells, bar your eggs or sperm) these mutations generally don’t even produce a noticeable effect. But, if the mutant gene is widespread enough, and is missense, it can have a major impact. Two examples of conditions linked to mosaicism are hemophilia, a blood-clotting disorder, and Marfan syndrome, which produces unusually long limbs.

Researchers complete 30% of the synthetic yeast chromosome — synthetic life is just around the corner

An international research effort to construct the first fully synthetic yeast is well under way. The scientists have fully designed the fungus’ genome and have already built five of its final sixteen chromosomes — planning to have the rest completed by the end of the year.

Image credits Paul / Pixabay.

Yeast has to be humanity’s favorite fungus. Sure, other shrooms taste better in a saute or make for a much more entertaining way to spend some free time, but yeast has been by our side since times immemorial. Whenever we’ve needed something fermented, yeast had our back. Without it, there would be no alcohol, no bread, no fish sauce!

Since modern industries need to ferment more stuff much faster and into a more varied range of end products than ever before (think biofuels, insulin, antibiotics, THC), scientists have spent the last two decades sequencing yeast genome to produce different strains useful for all these products. That still leaves us limited by much of the yeast’s genome, however, which nature sadly didn’t design for industrial applications — but not for long.

Led by NYU Langone geneticist Jef Boeke, PhD, and a team of more than 200 authors, the Synthetic Yeast Project (Sc2.0) has designed a full genome for a functioning synthetic version of Baker’s yeast (S. cerevisiae). The latest issue of seven papers coming from the group shows that they’ve successfully constructed almost one third of this genome — 5 out of 16 chromosomes. They plan to have the rest ready by the end of the year. The new round of papers consists of an overview paper and five individual ones describing the first assembly of synthetic yeast chromosomes synII, synV, synVI, synX, and synXII. A seventh paper provides a first look at the 3D structures of synthetic chromosomes in the cell nucleus.

“This work sets the stage for completion of designer, synthetic genomes to address unmet needs in medicine and industry,” says Boeke, director of NYU Langone’s Institute for Systems Genetics.

“Beyond any one application, the papers confirm that newly created systems and software can answer basic questions about the nature of genetic machinery by reprogramming chromosomes in living cells.”

Learning the A’s and C’s

Apart from the immediate utility of having a tailorable yeast strain to apply in industry, Baker’s yeast was selected because of it’s relative simplicity and similarity to human cells. Sc2.0’s researchers are akin to a group of genetic programmers — they add or remove parts of DNA from chromosomes to dictate new function or prevent diseases or weakness to various factors. It makes sense to start with a simple ‘program’ until you learn the basics, which you can then apply to more complex systems.

Three years ago, Sc2.0 successfully assembled the first synthetic chromosome (chromosome 3 or synIII) out of 272,871 base pairs — the blocks which make up DNA. This process starts with the researchers screening libraries of yeast strains to find which genes are most likely to have useful features. Then, they planning thousands of permutations in the genome in a process somewhat similar to very rapid evolution. Some of these changes introduce the new genes to make the yeast exhibit desired features, others remove bits of DNA which were shown not to have a function in past trials.

Stained polytene chromosomes.
Image credits Doc. RNDr. Josef Reischig, CSc.

After the computer models are finished, the team starts assembling the edited DNA sequence bit by bit until they have the whole thing. The completed sequences are then introduced into yeast cells, which handle synthesizing and finish building the chromosomes — the latest round of papers describes a major innovation in this last step.

Until now, the researchers had to finish building once piece of a chromosome before work could begin on the latter, severely limiting their speed. These sequential requirements bottle-necked the process and increased cost, Boeke said. So the team made efforts to “parallelize” chromosome assembly, with different labs around the world synthesizing different bits in strains which were then mated. The resulting yeast strains would in some instances have even more than one fully synthetic chromosome. A paper led by Leslie Mitchell, PhD, a post-doctoral fellow from Boeke’s lab at NYU Langone, described the construction of a strain containing three synthetic chromosomes.

“Steps can be accomplished at the same time in many locales and then assembled at the end, like networking laptops to create a global super computer,” says Mitchell.

Another paper describes how a team at Tsinghua University used the same parallelized method to synthesize chromosome synXII, which formed a molecule with more than a million base pairs (one megabase) in length when fully assembled — the longest synthetic chromosome ever made by humans. It’s still only 1/3,000 the length of a human chromosome, but it’s closer than we’ve ever come before.

The researchers also found that they can edit some dramatic changes into the yeast genome without killing the cells. They survived even when the team moved whole sections of DNA from one chromosome to another, DNA swaps between yeast species, often with very little effects on the cells.

There’s a huge potential to synthetic yeast. Scientists could tailor their genome to produce anything we need from drugs, to food, new materials, almost anything — just from sugar and raw materials. It could fundamentally change how we think about a lot of industries, potentially churning the same products as factories and labs from a humble barrel.

But the work performed under the Sc2.0 project also revolutionizes how we know about genome building and synthetic life. Yeast is simple, but the end goal is to one day move on to tailor-made plants, maybe even to perfect the human genome. But we’re still a long way from that. Right now, the team will focus on getting their yeast’s final A’s, T’s, G’s, and C’s in place.


Dragon Lizard

Climate change is reversing the sex of bearded dragons, a first

Rising temperatures are fundamentally changing the way Australia’s bearded lizards get their gender. Basically, the lizard’s sex is not dependent on their genes as before, but on temperature. In time, the male chromosome could disappear, as more and more females are bred – the preferred sex. What this means is that if temperatures reach a critical level, then the lizards could become extinct due to lack of males. This has never happened before and it’s as scary, as it is interesting.


Humans, like other mammals and some insects, have their sex determined based on their chromosomes. If there are two of the same chromosomes (XX), then the individual is a female, while a different pair (XY) entails a male. This is called genetic sex determination (GSD). Reptiles work differently – their sex is determined by the temperature of the incubating eggs. This is  temperature sex determination (TSD).  For instance, when turtle eggs are cold males hatch, while females hatch at higher temperatures. In crocodiles, this pattern is reversed.

Bearded lizards use GSD. If there are two Z chromosomes, then the lizard is born a male, while ZW renders a female. But when Jennifer Marshall Graves raised the temperature of incubating lizard eggs a notch, the GSD was overridden  to TSD. Effectively, the sex of the lizards depended on temperature. When the eggs are incubated at 34 degrees Celsius, the body seems to ignore the usual genetic instructions, and even though a lizard has ZZ chromosomes, the egg will hatch as a female. Previously, everybody thought GSD and TSD are mutually exclusive. This was 2007.

Now, Clare Holleley from the University of Canberra along with colleagues captured 131 wild bearded dragons from eastern Australia and analyzed their genetic makeup. They found 11 ZZ females. These lizards are indistinguishable from ZY females: they can mate with males, can lay eggs and nurture the young. That sounds innocent enough – just a freak of nature. But in reality, it’s a lot more complicated. And dangerous.

Bearded babies. Image: Mrs King Bio

Bearded babies. Image: Mrs King Bio

Holleley also bred dragon lizards in a controlled lab setting. At 30 degrees Celsius, all the eggs hatched as males. At 36 Celsius, all were female. In between, there was a mix. What’s freaky is that  within just one single generation, the W chromosome had completely disappeared, and the dragons had switched completely to TSD.

“It is often thought that once a species veers down the path of chromosomal sex determination, there’s no going back,” explains Melissa Wilson-Sayres from Arizona State University.

“But this paper suggests that not only is it possible for a population jump out of the chromosomal sex determination rut, but that it actually occurs in the wild,” says Wilson-Sayres. “It’s  fantastic because it shows how much variation can exist right below our noses.”

“This makes me think of the statements I’ve seen about trans individuals not being “truly male” or “truly female”, because of their (presumed) set of sex chromosomes,” she adds. “This research tells us that even with chromosomal sex determination, exceptions occur all the time. In the bearded dragon, the exception may even be a benefit, as ZZ females lay more eggs that ZW females. This tells us that we’re thinking much too simply if we say with confidence that only XX is female and XY is male.”

The paper warns that if climate change intensives, sex reversal could increase among all dragon lizard populations, completely wiping out the W chromosome generation by generation. In the wild, of course, this reversal might be more gradual than in the lab. In time, males will become rarer until the species will become predominantly female. Extinction is just a step away. Then again, this is a reptile behaviour, and reptiles have survived through various temperature fluctuations. But then again, the rate of warming we’re experiencing today is quite steep. There might be no time to adapt. This raises questions about reptile sex determination adaptation at large.

New Imaging Technique Reveals the True Form of Chromosomes

The X-Shape in which we usually see chromosomes depicted in is only a snapshot of their real complexity – a new method for visualizing them showed.

chromosome structure

A joint project involving the Babraham Institute, the University of Cambridge and the Weizmann Institute has produced the most beautiful and accurate models of chromosomes available up to date.

“The image of a chromosome, an X-shaped blob of DNA, is familiar to many but this microscopic portrait of a chromosome actually shows a structure that occurs only transiently in cells — at a point when they are just about to divide.”, explains Dr Peter Fraser of the Babraham Institute.

The team has developed a new, complex method of visualizing their shape, which involves creating thousands of molecular measurements of chromosomes in single cells, using the latest DNA sequencing technology. Blending in these microscopic measurements and supercomputers, they created a three-dimensional portrait of chromosomes for the first time.

“These unique images not only show us the structure of the chromosome, but also the path of the DNA in it, allowing us to map specific genes and other important features. Using these 3D models, we have begun to unravel the basic principles of chromosome structure and its role in how our genome functions.”

This latest research puts DNA in a proper visual context in a cell, showing the beauty and complexity which go hand in hand in the mammalian genome; it also highlights the effectiveness in which it works, and ultimately, how it is responsible for health, aging and chromosomal aberrations.

“Until now, our understanding of chromosome structure has been limited to rather fuzzy pictures, alongside diagrams of the all too familiar X-shape seen before cell division. These truer pictures help us to understand more about what chromosomes look like in the majority of cells in our bodies. The intricate folds help to unravel how chromosomes interact and how genome functions are controlled.”

Down Syndrome’s extra chromosome shut down in lab cells

The insertion of one gene can shut down the extra chromosome which causes Down Syndrome, according to a study published today in Nature.

A dreadful disease

dsDown Syndrome (DS), also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It’s the most common chromosome abnormality in humans, and it is commonly associated with a delay in cognitive ability (usually mental retardation), physical growth, and a set of distinctive facial characteristics. Down syndrome is named after John Langdon Down, the British physician who described the syndrome in 1866.

It’s estimated that approximately 1 in every 700 hundred babies are born with DS. There is no cure, no real improvement treatment, and while this method doesn’t provide a cure, it is the stepping stone in developing a treatment.

“It’s a strategy that can be applied in multiple ways, and I think can be useful right now,” says Jeanne Lawrence, a cell biologist at the University of Massachusetts Medical School in Worcester, and the lead author of the study.

First steps

Lawrence and her team devised an approach to mimic the natural process that silences one of the 2 X chromosomes carried by all female mammals (men carry XY instead of XX). Both chromosomes contain a gene called XIST (the X-inactivation gene), which, if activated, produces an RNA molecule which surrounds the the chromosome entirely, sealing it away from other reactions. In female mammals, one copy of the XIST gene is activated — silencing the X chromosome on which it resides.

The team then spliced the XIST gene into one of the three copies of chromosome 21 in cells from people suffering from Down Syndrome. They also inserted a genetic switch that allowed them to turn on XIST by dosing the cells with an antibiotic (doxycycline).

“The idea of shutting off a whole chromosome is extremely interesting” in Down’s syndrome research, says stem-cell researcher Nissim Benvenisty of Hebrew University in Jerusalem. He anticipates future studies that split altered cells into two batches — one with the extra chromosome 21 turned on, and one with it off — to compare how they function and respond to treatments.

Even though the experiment was successful on lab cells, the method has its drawbacks – turning on XIST may not block all gene expression in the extra chromosome, and the results are hard to estimate if this would happen.

Still, this is a promising step towards developing innovative, efficient treatment for people suffering from Down Syndrome.

Scientific reference: doi:10.1038/nature.2013.13406


Genetics might predict how long you’ll live. Trauma might shorten life span

Researchers at Duke University studied the telomeres – the tip of chromosomes that protect them  – in a group of children and found that those who had experienced trauma had their telomeres shorter than those that hadn’t. These chromosome tips, which can be viewed akin to shoelace tips, have been linked by scientists with aging and have been the subject of research for many scientists studying longevity.

TelomeresDo you remember those stupid internet quizzes where you would input your date of birth and some random facts about you , and then a tombstone with your name and expected decease date popped out? We’ve all had our laughs with it, and even shrieked at the sight of some friends which took them too serious, but could science predict how long an individual is supposed to live? A lot of factors are at play, of course. An instance of myself that smokes and doesn’t exercise will most likely have a shorter life span than an instance that eats healthy, exercises and doesn’t come in contact with stress. But is there a sort of default life span hard coded in our very genes?

This hidden secret might lie in telomeres, located the ends of chromosomes which make up our genes. Scientists have found for a while that there’s a link between aging and telomeres, which become shorter and shorter with each cell division. Some people shorten their telemores more than others, but an undisputed fact is that these go only way with age – down.

Scientists at Duke University may have come across a new fact that’s startling and surprising at the same time, namely that trauma might accelerate telomere shortening. For their research, the scientists sampled genes from 5-year olds and then again when they turned ten. Some of this children, unfortunately, were subjected to physical abuse or bullying, or had witnessed adults engage in domestic violence.

“We found that children who experience multiple forms of violence had the fastest erosion of their telomeres, compared with children who experienced just one type of violence or did not experience violence at all,” says Idan Shalev, the study’s lead author.

Now, their study group might not be spread enough to deliberate a sound conclusion, but coupled with a separate study their findings don’t seem that far off.  A study was conducted at Brigham and Women’s Hospital in Boston looked at a huge sample of 5,243 nurses nationwide and found that those suffering from phobias had significantly shorter telomeres than those who didn’t.

“The telomeres are essential for protecting chromosome ends,” says Carol Greider, a molecular biologist at the Johns Hopkins University and a pioneer telomere researcher awarded a share of the 2009 Nobel Prize in Physiology or Medicine. “When the telomere gets to be very, very short, there are consequences,” she says, noting the increased risk of age-related ailments.

Scientists have yet to come up with a pertinent explanation of how positive or negative experiences might influence telomere length, nevertheless a beckoning question arises – does destiny shape us or do we shape destiny?


via Smithsonian


Men’s Y chromosome stands its ground – men aren’t going extinct!

Good news for men, and especially women: the Y chromosome, which holds the male sex determining genes in most mammals, including humans, is not going extinct, as some claim, as a new research found that the diminishing gene numbers have come to a halt and will remain this way.

Sex chromosomes come in pairs, such men have X-Y and women have X-X. Around 320 million years ago when the first Y male determining chromosome appeared, both the X and Y chromosomes had roughly the same number of genes, actually sharing 800 genes. In time, the Y chromosome has lost 1,393 of its 1,438 original genes over the course of its existence. With a rate of genetic loss of 4.6 genes per million years, the Y chromosome may potentially lose complete function within the next 10 million years, or so some scientists claim. Currently, the human Y carries a mere 19 of its ancestral genes shared with the X chromosome, out of a once 800 strong, bringing the total number of genes in the human Y to 27.

This would mean that in a few million years, the world would be dominated by women alone, leaving only artificial reproduction as an exclusive option – highly practical, not all that fun. Fear not, for Jennifer Hughes at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, along with colleagues, have found that the Y chromosome is here to stay.

The researchers sequenced the Y chromosome of the rhesus macaque, a very close relative of humans, from which it diverged paths some 25 million years ago. It was found that the monkey’s Y has 20 genes shared with its X, of which 19 are shared with the human Y. This suggests that the human Y chromosome has lost only one gene since humans and macaques last shared a common ancestor. The research, thus, provides direct evidence that the linear extrapolation model is flawed.

“We finally have empirical data that the Y chromosome has held steady over the last 25 million years,” says Hughes. “Most of the Y chromosome’s gene loss happened almost immediately after it stopped recombining with the X chromosome.” The 19 surviving genes probably have vital biological functions, she says, and so aren’t going anywhere anytime soon.

Here’s to men!

The research was published in the journal Nature. Image credit.