海角大神

Humans, we know, have 23 pairs of chromosomes in each cell, including one pair of sex chromosomes: females have two X chromosomes, and males have an X and a Y chromosome.

What is less well known is that the X chromosome does not look like an 鈥淴.鈥�

Despite its moniker, the X chromosome鈥檚 shape has been a missing puzzle piece in genomics 鈥� as has, in fact, the shape of all chromosomes, the spools of protein that contain our DNA. Though scientists have had a general sense of the X chromosome鈥檚 structure (at least, scientists have long known that it wasn鈥檛 X-shaped), the exact placement of its flips and folds, its coils and curlicues, had remained unknown.

But a 聽describing the first 3D-model of the X chromosome changes that. The model is an enthralling portrait of just 鈥� smaller than a red blood cell but larger than a E. coli bacterium 鈥� that could help scientists鈥� effort to plot which genomic regions are involved in aging and disease, and how so.

That the X chromosome is not shaped like an 鈥淴鈥� upends popular renderings of the chromosome, but it is not a revelation to scientists. The tale of how the X chromosome came to be pictured as an 鈥淴鈥� is a long one, unfolding around 1890 when scientists were first piecing through the foreign language of our bodies and . It was called 鈥淴,鈥� a placeholder for 鈥渦nknown.鈥� Later, its brother chromosome was called 鈥淵,鈥� after the next letter in the alphabet.

Then, it turned out that chromosomes 鈥� all of them 鈥� are shaped like an 鈥淴,鈥� but for just a moment. This X-shaped structure is a pit stop right before an organism鈥檚 cells divide, in what is known as mitosis. The X-shape is also not one chromosome: it鈥檚 two. One of the two angled columns that make that 鈥淴鈥� is a new, identical copy of the other, made so that when the cell splits, one chromosome goes to one cell, and the other goes to the other cell.

All of a cell鈥檚 46 chromosomes must manufacture copies when a cell splits, which means that there are 92 chromosomes in the cell during mitosis, all nipped and tucked into X-shaped pairs.

The mitosis shape has been the preferred means of representing chromosomes, since this is the point at which each chromosome (or, really, pair of chromosomes) is distinguishable from another pair, and, no less, has been neatly packaged into a familiar shape.

鈥淲hat you normally see are these X-shaped X chromosomes, like blobby cylinders joined at the middle,鈥� says Peter Fraser, a researcher at the Babraham Institute, in the UK, and an author on the paper. 鈥淚t鈥檚 an easy way to show people what an X chromosome looks like.鈥�

But, once the cells have split, things get more complicated. Now, the chromosomes are unwound and un-cinched from their convenient bundles, glopping together so that it鈥檚 difficult to tell one chromosome from another. That has presented a problem not just for science textbooks, but also for scientists, who, while knowing that chromosomes look in general like pooled spaghetti, have not had an exact map for the twists and turns of an individual chromosome.

That's a problem since this complicated post-split state is the normal state of a cell, while the neat, mitosis state is just a brief one: at any given time, about 99.9 percent of the cells in a human are not dividing, says Dr. Fraser.

鈥淲e had no understanding of the chromosomes in a cell in its natural state,鈥� he said.

In the researcher, Fraser and colleagues at the Brabraham Institute, as well as at the University of Cambridge and the Weizmann Institute, used measurements of multiple X chromosomes from mice鈥檚 cells. The resulting model looks like a heap of threaded-up vermicelli. If there鈥檚 an X shape to be found, its buried in the lump.

The researchers also found that the X chromosomes in different cells varied from each other in shape and structure.

To explain what it means to have a chromosomal map, Fraser puts it like this: Let鈥檚 imagine a chromosome as the some 250,000 miles of road in the United Kingdom with each region in the chromosome being a house along these roads. So far, geneticists had been able to assign a number to each home, plotting them in order over 250,000 miles along what looks like just one long road.

But what if that road isn't straight at all, but coiled like a roller coaster squeezed in Godzilla鈥檚 grip? That would mean that house number one might neighbor house number 1,000, but be miles and miles from house number 10. If we want to know which houses abut each other, we'll need to have not just the house numbers, but also a map of the road's furls.

Now, let鈥檚 put this back in genomic terms. The X chromosome spans more than 153 million base pairs in the human genome, out of about 3.2 billion base pairs (in mice, the X chromosome鈥檚 length is about 168 million base pairs). Cramped up, chromosomal regions that would be right next to each other if the chromosome were pulled straight might actually be found tens of thousands of bases聽apart.

鈥淭his is a map of how the chromosome folds, which parts touch and where, and who is next to who,鈥� says Fraser.

Understanding what is connected to what in a chromosome, and where and how it is connected, is critical to understanding how the genome is regulated, which, in turn, is critical to understanding disease and aging, he said.

The X chromosome is a big chromosome 鈥� for comparison, the Y chromosome is about 50 million base pairs long 鈥� making it a prime candidate for an initial chromosomal model, says Fraser. The other chromosomes, which will be mapped, as well, are expected to also look like blobs of pasta, but to also be as individual, of course, as are different pasta blobs.