I've been seeing "Genome of X has been fully sequenced" articles over the course of some years. Can someone who understands it explain to a layman like myself how exactly this benefits us?
I think the best big picture explanation of why this is important is this: our ability to feed and care for humanity is dependent on biology. Genomes are the source code for biology. Reading the source code is the first step to understanding the source code. Understanding the source code will allow us to build better expressions of biology (those being both ourselves and the animals and plants we depend on).
I hope you won't take it personally because you're far from the only one to say it (and I would have refrained from posting if I hadn't seen people taking this further in this thread), but I really wish people stopped using the "DNA is the source code of your body" analogy. It is used way more than what's it's actually worth, even though I can see how that analogy can be seductive. The structure of a program's source code is nothing like the way DNA encodes and propagates information. Even if you add a bunch of adjectives such as 'self-modifying', 'full of GOTOs', 'nondeterministic', 'live monkeypatched', and thus twist the picture many people have of the way source code translates into execution, it would still be misleading. We are a product of both our genome and environment, at the same time, all the time. Not one then the other. Or, if you will, the source code is its own executable. It doesn't make sense because the analogy doesn't either.
And that's not even taking into account non-DNA things that encode and propagate information, such as microbiota or anything linked to epigenetics.
It’s actually a great analogy. Analogies aren’t supposed to be exact representations; they are supposed to allow you to quickly communicate a decent approximation of what something is by relying on preexisting understanding of how another thing works. The source code analogy does that well.
And, by the way, running programs are also the result of their source code and the environment in which they execute. It’s just that the environments which computer programs run in are very homogenous and predictable. But flip some bits in memory or have a user thrash the UI and you’ll see that a running program interacts with its environment in much the same way as a biological organism.
I never said it was a bad analogy, I even used a rather positive word ('seductive'). It is overrated, though, and it does stop making sense sooner than many people think. What I'm really saying is that relying on this analogy to understand how DNA works in relation to organism development, function, etc. won't get you past a very cursory understanding of it. It may be enough for many people but:
-I like to think that HN is filled with people who take interest in many things, especially science-related subjects, and would hope that many of them on this site would like to know more than an analogy-based understanding of genomics
-For better or for worse, the recent bloom and advances in genetics and biology in general have taken over the modern world and been hailed (probably with reason) by all kinds of circles, from the media to governments or the tech world, as a promising new era that's going to revolutionize our understanding of life, disease, what it means to be human, cognition, what have you. It does feel pretty cool as an insider to know that you're working in the 'hot new thing' but a side effect of that is, I have seen people develop a pretty bizarre fascination with DNA, whether it be their own or other people's. And it's not something that can be pinpointed to entirely rational reasons. I don't want to go off tangents any further, but let's say it can't hurt to occasionnally remind people what DNA is and what it isn't, what it's like and what it's definitely not like. I dislike pedants as much as the next person but seeing so many (presumably very educated) people take that analogy in the same thread made me think that the reminder wasn't that out of place.
I disagree, DNA is pretty much the source code. any differential DNA expression are due to histone modification, proteins, or RNA (and rarely CpG DNA modification in humans) so DNA in the purest form is indeed the source code.
Source code for what, though? How about pre-natal influences in the womb, does this mean the womb is a sort of compiler? What about the structure of DNA itself, known to influence gene expression levels? What about the microbiota, which is arguably more 'you' than your own body in terms of raw cell count? What about the phages found in the microbiota (the phageome)? Why are they not part of the so-called source code?
Source code/machine code, I am just interchanging but in this analogy they are equivalent. Pre-natal influences change the epigenetics, i.e. "on" the genome. The structure of DNA is almost completely determined by histones, which are proteins that DNA wrap around, so once again, not the DNA. Microbiota affect the environment of the cells, meaning it is an input to the cell, not the source code. Any phages affecting the microbiota will affect the input to the cell. These factors aren't considered source code simply because it only affects the execution of the cell's source code.
And even more so, a product of our cells and RNA soup and so on. There's a truly huge operating system that DNA operates in. I think of DNA, when I think of it as all in a coding way, as a top-level script on top of enormous machinery. Like a switch on a giant factory, that says 'man' when you flip it one way and 'mouse' when flipped the other. Does the switch encode what it means to be a man? a mouse? No.
Yeah, but the question is: having the source code in the form of a bunch of files (each containing some routines) OR having it in the form of a bag of routines, is that a significant difference?
(To see the analogy, substitute file = chromosome, and routine = gene)
Try to see the anti-gene-modification initiatives as a security by obscurity approach.
Seeing the horrors of info-security (drm, attacks, cheap-hacks) today unfolding, and imagining a nature, where wild gene drives are on the loose, this approach seems misguided but at its core valid.
The one time loss of half the biosphere that will occur with the source code being readable is greater then any gain.
A great book to get more into the dangers of genetic editing and proprietary genes:
It is the very first step to all kinds of genetic analyses, especially for anything comparative. Usually with most species, we only have access to 'bits' of the genome rather than the whole chromosomes - a shortcoming of current short-read sequencing technologies. This means it's hard to get a broad picture of things like large-scale sequence rearrangements within the genome. There's a whole range of emerging technologies trying to alleviate that though, but aggregating them all together is a mind-numbing hassle.
The end result, though, is that now that we have access to a high quality picture of what sequences belong to what chromosomes, we can compare other varieties to that reference, see what structural differences (that really means 'sequences moving around') occurred over the course of evolution, when they occurred, why (in evolution terms) they may have occurred, and so on. Understanding that is key to do all kinds of cool experiments (or from an industrial perspective, optimizations) that weren't accessible to us previously, and the stakes are very high when dealing with such a staple crop that feeds billions of people.
Also, many varieties of wheat are hexaploid - their chromosomes come by six, instead of two for us humans. This isn't that exceptional for plants, but it means sorting out the chromosomes with the right alleles when almost each sequence is more or less replicated six times is, as the article title says, a nightmare of complexity. So even if you skip what others and I have said before, it is a technical prowess and it sets a very hopeful precedent for future projects involving other species of similar complexity, and many crops and plants happen to belong to that category.
Genomes are used as a reference point for all sorts of genetic analysis. It's comparable to having the source code to a binary. Plant breeding in particular benefits from having better analytical tools on hand, since it's such a critical field with such a gargantuan and diverse pool of organisms to study.
In that analogy, perhaps it's more like having successfully read out every byte of a binary that was encoded onto a medium that is extremely to read off of.
Having the source code... I'm not sure what that would be analogous to, but it would probably quite a long way off.
The genome is akin to the software of an organism. It's not exactly obfuscated, so we can actually learn a lot just by reading it. The next big benefits are all about relating the genome of one organism to others.
A single "reference" genome can serve as a high quality basis for interpreting new genomes. This is called resequencing. Small pieces of the new genomes are sequenced with very cheap techniques and mapped into the most-similar bits of the big genome, in effect allowing for a kind of guided reconstruction of the new genome. The short read lengths make it difficult to reconstruct a new genome de novo, but that's OK because if we have a reference we've already paid that price once for a related individual.
This process has bias but it's also expedient, say when you have thousands or millions of genomes in a study (as happens in agriculture).
One big problem in the field now is this obsession with reference genomes and resequencing against them. Researchers forget how much the reference genome can bias their resolution of a new genome. This has resulted in a lot of fussing and fixation on high-entropy regions of genomes and small variations (point mutations, or SNPs) within them. There is a growing body of evidence that suggests that large changes are probably more important for adaptation, but they remain somewhat underappreciated because of this short read resequencing modality.
I recently started working in a related field (RNA sequencing) and none of the other responses have really captured "what" it is that's going on here - and that's kinda necessary for the "why". When we say that the human genome project sequenced the human genome and completed in 2001/2002, what they mean is that there are databases with 23 sequences of A,C,T,G's for each of the 23 chromosomes plus another for the mitrochondrial DNA. This is "half" the DNA for a single person - or more accurately it was a composite of various parts of a couple people, in the case of the human genome project. It's only half because it's just one of the two sets of chromosomes that we get from our parents. It's not the genetic code of every person out there, just of one "reference" one. Variation within a species is quite low, so this is still extremely useful: chances are my genome looks a lot like the reference genome so if you want to talk about my genome, you can talk about it in terms of the reference genome. We can say that I have a SNP (single nucleotide polymorphism) where my DNA differs from yours in a single nucleotide (like switching an A for a C). It gives us a framework for talking about the genetic code of individuals of the species - we can say that the protein that does X is encoded in the gene at position Y on chromosome 12.
You can view the human genome at UCSC genome browser [1] and zoom in to the "base" level to see the actual sequence. It has lots of "annotations" where projects have marked where genes are (most of the genetic code does not encode proteins, genes are the parts that do, the rest is less well understood). You can see data there that shows you which parts of the genome vary from one species to another (generally mammals will be very similar to us in genes and less so between genes where the DNA is "less important" and so changes there don't result in death, so looking at where things are "conserved" by evolution tells you where the most fragile and important parts of the genome are, to a first guess).
What "they don't tell you" is that it's still not really complete. For example, there are bits of genetic sequence that we know go somewhere in the genome, but we don't know where. The way we sequence DNA, you only get to read little pieces at once and then have to string them together to reconstruct the whole thing. But one problem is repeats: sometimes the genome just goes "ATATATATATATATAT...." and if there are more there than the length of each piece you can read, it becomes impossible to know how many there are in total. Ambiguities like this exist because our DNA isn't just random strings of data, it has lots of structure that repeats from one place to another. So it can be impossible to tell where exactly a piece of DNA belongs, given the limited information we have. Also the annotations of where genes are is very much not finalized.
There are other problems with the sequences. For example, they'll include "N" to mean "some base, we don't know which" - there are millions of N's at the start of the chromosomes I've looked at. In reality, we all have some actual code there, but it's never been sequenced for anyone. Other structures confuse us: there is DNA encoding for ribosomal RNA which is used in ribosomes which are used to go from genetic code to actual proteins. So your body needs lots of ribosomes to keep everything being made so it needs lots of copies of the ribosomal DNA to produce enough ribosomal RNA - like 500 copies in a row. And it has those not just in one chromosome but in multiple. But the human genome project doesn't show it like that as it really should be: it has about half of one copy in the right spot. And then the rest of it is just spread in short bits throughout the rest of the places the code occurs. This causes problems if you are doing research and don't know what it is you're looking at, since it looks out of place. It's a complete mess. But despite that, it's good enough to do so much with.
Here's one use for a fully sequenced genome: RNA sequencing (which, I'll reiterate, I just started working on this a month ago so I've probably said at least one false thing already). RNA is made from DNA and proteins are made from RNA. So if you want to know what proteins are in a cell - and they're the things that actually do the work - then you can look at what RNA is present. This is easier these days than checking the proteins themselves. But RNA on its own doesn't tell you a lot, so you "align" the RNA to a reference genome: given a little piece of RNA (like 100 nucleotide bases long), where does it fit in the genome? It often has a unique spot it could have come from, so now you know what DNA was turned into what RNA. If there's a gene there, then you know what gene is being "expressed," meaning turned into protein via RNA. Genes don't do much if they're not expressed, so this is very useful to know to understand what is happening in a cell. Looking at RNA sequencing versus DNA sequencing is like looking at what software is running on your computer versus looking at what code is stored on the hard disk. Both tell you a lot and understanding what code is on the hard disk will help you understand what you're looking at when you're looking at what code is running, like "Oh, these operations belongs to the bash executable - so bash must be running".
[1] https://genome.ucsc.edu/cgi-bin/hgGateway (hit GO if you just want a piece of human DNA, hit "base" button in zoom in if you want to see actual sequences but that's too close to see much of the structure that the annotations provide)
The current treatment is strict dietary exclusion of all protein from wheat, barley, rye and other related grains. It’s conceivable that wheat could be modified to produce proteins that are not immunogenic to celiac sufferers.
The challenge would be making sure that only that modified wheat was harvested. I'm sure it could be done, but a needle in a haystack seems much easier to find than a conventional wheat in a celiac friendly wheat stack.
I'm not sure genetic mapping is really the core of the issue anyway. What we need is the equivalent of a reverse vaccination, since celiac is essentially an immunity to wheat. Such a concept might do for chronic disease what vaccination did for acute.
Sure, that would be difficult. Keeping wheat out of even dissimilar grains is currently a challenge for food producers and processors. The test would be the same, though, as testing any other grain for contamination, which is routine - test for gluten.
“Future potential treatments for patients with RCD include the development of genetically detoxified grains, oral and intranasal 'coeliac vaccines' to induce tolerance, inhibitors of TTG, and detoxification of immunogenic gliadin peptides via oral peptidase supplement therapy.”
Nope. Phylogenetic families are based on the degree of shared ancestry, not the presence or absence of any given trait.
I mean, don't get me wrong, you CAN develop phylogenetic trees based on traits. That's how Linnaeus and all subsequent taxonomists did it before they could just look directly at DNA. But it takes a lot of traits, and has been preempted by DNA based methods anyway.
> Phylogenetic families are based on the degree of shared ancestry, not the presence or absence of any given trait.
What about the rhyme “Sedges have edges, rushes are round, and grasses are hollow right down to the ground?” You’re telling me scientists are now saying that DNA testing is more accurate than just using the rhyme?
It is not about DNA vs phenotypes. The issue is that biologists are more interested in building an universal classification, a single tree of life for all species, than they are in building single-phenotype-based classifications that dont nest particularly well.
For example, if you looked at just the ability to fly, you would group birds and bats on a same group. But that would be wrong because bats are clearly more closely related to flightless mammals than they are to birds. This becomes obvious if you account for more characteristics of the animal (presence of fur, bone shape, pregnancy, etc) or if you examine the DNA.
Yes, NRGene is an Israeli company, so that would make sense.
NRGene has a proprietary algorithm that uses a large amount of Illumina sequences to build a pretty good genome assembly. This technology has been used in a few organisms with large genomes, as it has been used in v1.0 of this assembly.
However there have been previous, less high quality wheat genome assemblies based on Bacterial Artificial Chromosomes (BACs), and that information has made its way into this assembly too, along with long-distance information from HiC and genetic maps and Bionano technology.
As a longtime celiac sufferer, it would be in my best interest and that of my descendants for all of those varieties to be eradicated, like smallpox. There’s nothing especially beneficial about wheat as a food, and it has drawbacks, such as how it is the only food I can think of with its own autoimmune disease.
I can't say I support your desire to eradicate wheat. I love bread, and without bread probably half the human population would starve. Most of the rest would likely die in the resulting upheaval.
There was a scifi story about such a scenario, I think it was entitled "No Blade of Grass" by John Christopher.
No, wheat is not crucial in a way that people would starve if it were not available. There are dozens of other foods that could be grown which would provide equivalent nutritional benefit. It is not a unique or particularly advantageous source of any nutrition. It does not have any unique advantageous growing properties.
Additionally, while many people are not familiar with cereal grains other than the close wheat family, there is really nothing that different about their flavor or how they taste in cooking. The only useful, unique thing about wheat is that the protein provides a texture in baked goods and sauces that people find pleasant. When forced to explore alternative grains for a couple of years, and having eaten my mothers alternative grain cooking before that, I learned that the gluten-free foods often actually taste better. Wheat is necessary and flavorful like Windows is user friendly and required for your computer to function.
If you put my comment in context, I am not intending to advocate any sort of eradication program for wheat. I’m responding with mild hyperbole to the notion that it is particularly critical to preserve wheat. The main idea that I am promoting here is that there’s nothing special about wheat, other than that it is particularly harmful to some people.
As a child I was allergic to all dairy products with serious eczema from head to toe, even a drop of dairy would initiate it, entire body covered in scabs, arms in wet bandage inner-wrapping, dry outer bangage should I get exposed to even a little milk product. Yet I do not want all dairy products to be banned, they bring valuable nutrition to diverse groups of people, I was just unlucky, but very lucky to be born in a country with a health service that cares.
Wheat is a wonderful food, extremely nutritious, that has been the cornerstone of the development of multiple civilisations.
Wheat is not wonderfully nutritious. It provides nothing special and is even somewhat problematic.
If the global food industry was capable of keeping wheat out of their food, that would be fantastic. Unlike dairy, almost all dry foods are contaminated with gluten unless you go to lengths to obtain food that is not.
You're speaking from the perspective of someone who always has enough to eat, so you have the privilege of optimizing for nutrient ratios. Billions of other people aren't so lucky, and they just need more calories period. Wheat is great that, along with rice, soybeans, and other staple crops that are better in the growing/volume sense than in the nutritional sense. Not all of humanity can afford boutique heirloom artisanal hand-grown crops that are $10 per pound.
If we're going to optimize for anything, it's for feeding as many people as possible -- there are far fewer celiac sufferers than there are people who go without enough food. Optimizing the food chain to protect you would result in many more people dying from starvation, because you'd be eliminating an efficient, widely grown crop that feeds many. Wheat is the second most important crop in the world, behind only rice.
Actually, I’m speaking from the perspective of someone who is dying from starvation despite being surrounded by available food.
There is nothing special about wheat. All of the resources spent on growing wheat could be expended on many other crops which would provide equal or greater nutritional benefit. The reason wheat is a globally important crop is simply because people have made it that way for arbitrary reasons, like raising European cattle in North America.
The problems I am referring to are celiac and non-celiac gluten sensitivity. There are at least a dozen other grains that provide the benefits of wheat without those disadvantages, and that is to what I am referring. Rice, corn, sorghum, buckwheat, millet, teff, quinoa, lentils, and and so on.
So the "even somewhat problematic" part of wheat is problematic to only 1% of the entire population and that's an argument to kill off all wheat, yeah, no, try again.
The article says wheat has 5x the human genome. I assume that means it’s very high in protein. Isn’t that what most of the world needs, as opposed to mostly carbohydrates?
High in protein compared to what? Is wheat better than millet, sorghum, quinoa, teff, oats, corn, and rice, or is it just a European tradition to base cuisine on wheat?
I’m not an agricultural or genetic expert and I have no idea what relation genome complexity has to proteins or how that makes it useful to humans. Overall wheat is not very high in protein... it’s a crop grown for carbohydrates. If you were trying to fulfill your daily protein needs from wheat, you’d fall quite short. I suppose it complements more adequate sources. The protein it does have - gluten - isn’t especially digestible compared to alternatives like corn or rice, though it does have a texture that people find pleasant or useful in baking. Crops like lentils and soy are what you grow if you want to grow protein.
Wheat has a decent protein-to-carbohydrate ratio and you can make seitan from it, which is a great alternative to tofu / tempeh and other legume-based protein sources.
Sure, seitan (aka wheat gluten) is a protein source.
How many other grains have a decent protein to carbohydrate ratio though, and are more easily digestible, and don’t cause crippling autoimmune disease or digestive dysfunction in 1-5% of people? You can get concentrated protein from any grain with similar nutritional benefits.
Personally, my sensitivity to gluten has just about ruined my life - right now, my life is on hold and I am staying in a hotel in Rochester while obtaining treatment from the Mayo Clinic’s celiac specialists. Not sure that anyone can say that about quinoa or millet.
no, it means nothing of that sort, it just means the DNA is five times longer, not that there are five time as many genes encoding five times as many proteins. It is more like there is more DNA padding around the genes as a protection from virus which tend to jump limited distances along a genome.
sorry for leading with a negative, I know it can come across more strongly than I intend.
Assuming you're referring to the Svalbard Global Seed Vault, the Wikipedia page answers your question:
> In October 2016, the seed vault experienced an unusually large degree of water intrusion due to higher than average temperatures and heavy rainfall .... The vault was designed for water intrusion and as such the seeds were not at risk.
If things go far enough downhill that the Svalbard vault is lost and its contents just allowed to rot, I’d be surprised if we retained the technological capacity to do things like synthesizing a complex genome from data. (I’m not sure we could do that with present technology either, for that matter.)
Libraries and museums burn down all the time, or get destroyed in wars. Consider the recent fire at the Hewlett-Packard museum, where all the paper history was lost. Nobody made a backup, even though paper lasts longer term than data on a hard drive.
Frankly, I think storing data as ASCII in pits on a substrate is a great long term solution, as it can be read with a simple optical microscope, and ASCII is forever.
One of the cool things about digital data is it can be copied forward limitlessly. Make the seed genomes public domain and put them on a server - people will make copies, like they make copies of wikipedia to store in their prepper bunkers.
Even with the digital copy of the genome, you have to synthesize the entire genome, the cell it belongs in, and the rest of the seed to get a plant. That seems... possible, but hard enough that it doesn't make sense to call the sequenced genome a "backup".
No. You need a wheat cell as well. Then you might be in business.
And, no, it is not possible (today) to rebuild a multi gigabase hexaploid genome. The best that's been done so far is mycoplasma (500kb genome, which is many orders of magnitude smaller).
Also, the "genome sequence" presented here is not really complete. Thus far only the simplest organisms have had their genomes synthesized from a digital template and resulted in a viable cell. We rarely can produce a "complete" genome for anything other than bacteria and viruses. And for those, the diversity in the population makes the idea of establishing a single genome sequence somewhat limiting.
Today? No. Likely the so-called "junk DNA" was skipped over and we are still learning what the impact of environment and hormones is on gene expression.
What we can do today is to manipulate DNA and re-inject into an egg. Although not nothing, this is not "just its genome."
Sure it's possible. (I've recreated programs from source despite lacking the compiler, etc., originally used on it. The trick is to adapt something else to the task.) The source contains instructions on how it works, and those instructions can be used elsewhere.
I've been seeing "Genome of X has been fully sequenced" articles over the course of some years. Can someone who understands it explain to a layman like myself how exactly this benefits us?
I think the best big picture explanation of why this is important is this: our ability to feed and care for humanity is dependent on biology. Genomes are the source code for biology. Reading the source code is the first step to understanding the source code. Understanding the source code will allow us to build better expressions of biology (those being both ourselves and the animals and plants we depend on).
I hope you won't take it personally because you're far from the only one to say it (and I would have refrained from posting if I hadn't seen people taking this further in this thread), but I really wish people stopped using the "DNA is the source code of your body" analogy. It is used way more than what's it's actually worth, even though I can see how that analogy can be seductive. The structure of a program's source code is nothing like the way DNA encodes and propagates information. Even if you add a bunch of adjectives such as 'self-modifying', 'full of GOTOs', 'nondeterministic', 'live monkeypatched', and thus twist the picture many people have of the way source code translates into execution, it would still be misleading. We are a product of both our genome and environment, at the same time, all the time. Not one then the other. Or, if you will, the source code is its own executable. It doesn't make sense because the analogy doesn't either.
And that's not even taking into account non-DNA things that encode and propagate information, such as microbiota or anything linked to epigenetics.
It’s actually a great analogy. Analogies aren’t supposed to be exact representations; they are supposed to allow you to quickly communicate a decent approximation of what something is by relying on preexisting understanding of how another thing works. The source code analogy does that well.
And, by the way, running programs are also the result of their source code and the environment in which they execute. It’s just that the environments which computer programs run in are very homogenous and predictable. But flip some bits in memory or have a user thrash the UI and you’ll see that a running program interacts with its environment in much the same way as a biological organism.
I never said it was a bad analogy, I even used a rather positive word ('seductive'). It is overrated, though, and it does stop making sense sooner than many people think. What I'm really saying is that relying on this analogy to understand how DNA works in relation to organism development, function, etc. won't get you past a very cursory understanding of it. It may be enough for many people but:
-I like to think that HN is filled with people who take interest in many things, especially science-related subjects, and would hope that many of them on this site would like to know more than an analogy-based understanding of genomics
-For better or for worse, the recent bloom and advances in genetics and biology in general have taken over the modern world and been hailed (probably with reason) by all kinds of circles, from the media to governments or the tech world, as a promising new era that's going to revolutionize our understanding of life, disease, what it means to be human, cognition, what have you. It does feel pretty cool as an insider to know that you're working in the 'hot new thing' but a side effect of that is, I have seen people develop a pretty bizarre fascination with DNA, whether it be their own or other people's. And it's not something that can be pinpointed to entirely rational reasons. I don't want to go off tangents any further, but let's say it can't hurt to occasionnally remind people what DNA is and what it isn't, what it's like and what it's definitely not like. I dislike pedants as much as the next person but seeing so many (presumably very educated) people take that analogy in the same thread made me think that the reminder wasn't that out of place.
I disagree, DNA is pretty much the source code. any differential DNA expression are due to histone modification, proteins, or RNA (and rarely CpG DNA modification in humans) so DNA in the purest form is indeed the source code.
Source code for what, though? How about pre-natal influences in the womb, does this mean the womb is a sort of compiler? What about the structure of DNA itself, known to influence gene expression levels? What about the microbiota, which is arguably more 'you' than your own body in terms of raw cell count? What about the phages found in the microbiota (the phageome)? Why are they not part of the so-called source code?
Source code/machine code, I am just interchanging but in this analogy they are equivalent. Pre-natal influences change the epigenetics, i.e. "on" the genome. The structure of DNA is almost completely determined by histones, which are proteins that DNA wrap around, so once again, not the DNA. Microbiota affect the environment of the cells, meaning it is an input to the cell, not the source code. Any phages affecting the microbiota will affect the input to the cell. These factors aren't considered source code simply because it only affects the execution of the cell's source code.
The source code for the organism.
And even more so, a product of our cells and RNA soup and so on. There's a truly huge operating system that DNA operates in. I think of DNA, when I think of it as all in a coding way, as a top-level script on top of enormous machinery. Like a switch on a giant factory, that says 'man' when you flip it one way and 'mouse' when flipped the other. Does the switch encode what it means to be a man? a mouse? No.
Is it better to say DNA is input data and epigenetics is the actual application?
Or is it opposite?
DNA is not input data, it is simply the source code. Epigenetics is the state/memory. The environment is the input data.
Yeah, but the question is: having the source code in the form of a bunch of files (each containing some routines) OR having it in the form of a bag of routines, is that a significant difference?
(To see the analogy, substitute file = chromosome, and routine = gene)
Great explanation, thanks.
Try to see the anti-gene-modification initiatives as a security by obscurity approach.
Seeing the horrors of info-security (drm, attacks, cheap-hacks) today unfolding, and imagining a nature, where wild gene drives are on the loose, this approach seems misguided but at its core valid.
The one time loss of half the biosphere that will occur with the source code being readable is greater then any gain.
A great book to get more into the dangers of genetic editing and proprietary genes:
https://en.wikipedia.org/wiki/The_Windup_Girl
It is the very first step to all kinds of genetic analyses, especially for anything comparative. Usually with most species, we only have access to 'bits' of the genome rather than the whole chromosomes - a shortcoming of current short-read sequencing technologies. This means it's hard to get a broad picture of things like large-scale sequence rearrangements within the genome. There's a whole range of emerging technologies trying to alleviate that though, but aggregating them all together is a mind-numbing hassle.
The end result, though, is that now that we have access to a high quality picture of what sequences belong to what chromosomes, we can compare other varieties to that reference, see what structural differences (that really means 'sequences moving around') occurred over the course of evolution, when they occurred, why (in evolution terms) they may have occurred, and so on. Understanding that is key to do all kinds of cool experiments (or from an industrial perspective, optimizations) that weren't accessible to us previously, and the stakes are very high when dealing with such a staple crop that feeds billions of people.
Also, many varieties of wheat are hexaploid - their chromosomes come by six, instead of two for us humans. This isn't that exceptional for plants, but it means sorting out the chromosomes with the right alleles when almost each sequence is more or less replicated six times is, as the article title says, a nightmare of complexity. So even if you skip what others and I have said before, it is a technical prowess and it sets a very hopeful precedent for future projects involving other species of similar complexity, and many crops and plants happen to belong to that category.
Genomes are used as a reference point for all sorts of genetic analysis. It's comparable to having the source code to a binary. Plant breeding in particular benefits from having better analytical tools on hand, since it's such a critical field with such a gargantuan and diverse pool of organisms to study.
In that analogy, perhaps it's more like having successfully read out every byte of a binary that was encoded onto a medium that is extremely to read off of.
Having the source code... I'm not sure what that would be analogous to, but it would probably quite a long way off.
The genome is akin to the software of an organism. It's not exactly obfuscated, so we can actually learn a lot just by reading it. The next big benefits are all about relating the genome of one organism to others.
A single "reference" genome can serve as a high quality basis for interpreting new genomes. This is called resequencing. Small pieces of the new genomes are sequenced with very cheap techniques and mapped into the most-similar bits of the big genome, in effect allowing for a kind of guided reconstruction of the new genome. The short read lengths make it difficult to reconstruct a new genome de novo, but that's OK because if we have a reference we've already paid that price once for a related individual.
This process has bias but it's also expedient, say when you have thousands or millions of genomes in a study (as happens in agriculture).
One big problem in the field now is this obsession with reference genomes and resequencing against them. Researchers forget how much the reference genome can bias their resolution of a new genome. This has resulted in a lot of fussing and fixation on high-entropy regions of genomes and small variations (point mutations, or SNPs) within them. There is a growing body of evidence that suggests that large changes are probably more important for adaptation, but they remain somewhat underappreciated because of this short read resequencing modality.
I recently started working in a related field (RNA sequencing) and none of the other responses have really captured "what" it is that's going on here - and that's kinda necessary for the "why". When we say that the human genome project sequenced the human genome and completed in 2001/2002, what they mean is that there are databases with 23 sequences of A,C,T,G's for each of the 23 chromosomes plus another for the mitrochondrial DNA. This is "half" the DNA for a single person - or more accurately it was a composite of various parts of a couple people, in the case of the human genome project. It's only half because it's just one of the two sets of chromosomes that we get from our parents. It's not the genetic code of every person out there, just of one "reference" one. Variation within a species is quite low, so this is still extremely useful: chances are my genome looks a lot like the reference genome so if you want to talk about my genome, you can talk about it in terms of the reference genome. We can say that I have a SNP (single nucleotide polymorphism) where my DNA differs from yours in a single nucleotide (like switching an A for a C). It gives us a framework for talking about the genetic code of individuals of the species - we can say that the protein that does X is encoded in the gene at position Y on chromosome 12.
You can view the human genome at UCSC genome browser [1] and zoom in to the "base" level to see the actual sequence. It has lots of "annotations" where projects have marked where genes are (most of the genetic code does not encode proteins, genes are the parts that do, the rest is less well understood). You can see data there that shows you which parts of the genome vary from one species to another (generally mammals will be very similar to us in genes and less so between genes where the DNA is "less important" and so changes there don't result in death, so looking at where things are "conserved" by evolution tells you where the most fragile and important parts of the genome are, to a first guess).
What "they don't tell you" is that it's still not really complete. For example, there are bits of genetic sequence that we know go somewhere in the genome, but we don't know where. The way we sequence DNA, you only get to read little pieces at once and then have to string them together to reconstruct the whole thing. But one problem is repeats: sometimes the genome just goes "ATATATATATATATAT...." and if there are more there than the length of each piece you can read, it becomes impossible to know how many there are in total. Ambiguities like this exist because our DNA isn't just random strings of data, it has lots of structure that repeats from one place to another. So it can be impossible to tell where exactly a piece of DNA belongs, given the limited information we have. Also the annotations of where genes are is very much not finalized.
There are other problems with the sequences. For example, they'll include "N" to mean "some base, we don't know which" - there are millions of N's at the start of the chromosomes I've looked at. In reality, we all have some actual code there, but it's never been sequenced for anyone. Other structures confuse us: there is DNA encoding for ribosomal RNA which is used in ribosomes which are used to go from genetic code to actual proteins. So your body needs lots of ribosomes to keep everything being made so it needs lots of copies of the ribosomal DNA to produce enough ribosomal RNA - like 500 copies in a row. And it has those not just in one chromosome but in multiple. But the human genome project doesn't show it like that as it really should be: it has about half of one copy in the right spot. And then the rest of it is just spread in short bits throughout the rest of the places the code occurs. This causes problems if you are doing research and don't know what it is you're looking at, since it looks out of place. It's a complete mess. But despite that, it's good enough to do so much with.
Here's one use for a fully sequenced genome: RNA sequencing (which, I'll reiterate, I just started working on this a month ago so I've probably said at least one false thing already). RNA is made from DNA and proteins are made from RNA. So if you want to know what proteins are in a cell - and they're the things that actually do the work - then you can look at what RNA is present. This is easier these days than checking the proteins themselves. But RNA on its own doesn't tell you a lot, so you "align" the RNA to a reference genome: given a little piece of RNA (like 100 nucleotide bases long), where does it fit in the genome? It often has a unique spot it could have come from, so now you know what DNA was turned into what RNA. If there's a gene there, then you know what gene is being "expressed," meaning turned into protein via RNA. Genes don't do much if they're not expressed, so this is very useful to know to understand what is happening in a cell. Looking at RNA sequencing versus DNA sequencing is like looking at what software is running on your computer versus looking at what code is stored on the hard disk. Both tell you a lot and understanding what code is on the hard disk will help you understand what you're looking at when you're looking at what code is running, like "Oh, these operations belongs to the bash executable - so bash must be running".
[1] https://genome.ucsc.edu/cgi-bin/hgGateway (hit GO if you just want a piece of human DNA, hit "base" button in zoom in if you want to see actual sequences but that's too close to see much of the structure that the annotations provide)
Perhaps the mapping will yield new treatments for celiac disease?
Perhaps the mapping will yield improvements against blight and pests, improving crop yields and reducing human hunger?
The current treatment is strict dietary exclusion of all protein from wheat, barley, rye and other related grains. It’s conceivable that wheat could be modified to produce proteins that are not immunogenic to celiac sufferers.
The challenge would be making sure that only that modified wheat was harvested. I'm sure it could be done, but a needle in a haystack seems much easier to find than a conventional wheat in a celiac friendly wheat stack.
I'm not sure genetic mapping is really the core of the issue anyway. What we need is the equivalent of a reverse vaccination, since celiac is essentially an immunity to wheat. Such a concept might do for chronic disease what vaccination did for acute.
Sure, that would be difficult. Keeping wheat out of even dissimilar grains is currently a challenge for food producers and processors. The test would be the same, though, as testing any other grain for contamination, which is routine - test for gluten.
As far as future treatments, this clinical review https://www.gponline.com/coeliac-disease-clinical-review/gi-... concludes that
“Future potential treatments for patients with RCD include the development of genetically detoxified grains, oral and intranasal 'coeliac vaccines' to induce tolerance, inhibitors of TTG, and detoxification of immunogenic gliadin peptides via oral peptidase supplement therapy.”
> For example, about 26 genes are differentially active in wheat varieties with solid stems and those with hollow stems
If it has a solid stem, wouldn’t it no longer be in the grass family by definition?
Nope. Phylogenetic families are based on the degree of shared ancestry, not the presence or absence of any given trait.
I mean, don't get me wrong, you CAN develop phylogenetic trees based on traits. That's how Linnaeus and all subsequent taxonomists did it before they could just look directly at DNA. But it takes a lot of traits, and has been preempted by DNA based methods anyway.
> Phylogenetic families are based on the degree of shared ancestry, not the presence or absence of any given trait.
What about the rhyme “Sedges have edges, rushes are round, and grasses are hollow right down to the ground?” You’re telling me scientists are now saying that DNA testing is more accurate than just using the rhyme?
It is not about DNA vs phenotypes. The issue is that biologists are more interested in building an universal classification, a single tree of life for all species, than they are in building single-phenotype-based classifications that dont nest particularly well.
For example, if you looked at just the ability to fly, you would group birds and bats on a same group. But that would be wrong because bats are clearly more closely related to flightless mammals than they are to birds. This becomes obvious if you account for more characteristics of the animal (presence of fur, bone shape, pregnancy, etc) or if you examine the DNA.
Seems like they're just bending the facts to conform to their observations.
Israeli press gives lots of credit to Bioinformatics company NRGene.
Yes, NRGene is an Israeli company, so that would make sense.
NRGene has a proprietary algorithm that uses a large amount of Illumina sequences to build a pretty good genome assembly. This technology has been used in a few organisms with large genomes, as it has been used in v1.0 of this assembly.
However there have been previous, less high quality wheat genome assemblies based on Bacterial Artificial Chromosomes (BACs), and that information has made its way into this assembly too, along with long-distance information from HiC and genetic maps and Bionano technology.
Yep I’m not qualified to tell facts from PR on this one (which is why I made that comment)
It's necessary to sequence all these so presumably they can be recreated if/when they go extinct.
Seems like many other dire circumstances would have to befall the earth before any of the global top 3 crops become extinct.
There are many, many varieties of wheat. They all need to preserved, because they have many different strengths/weaknesses.
Having a monoculture of crops is a terrible vulnerability. Look at what is happening with our current monoculture of bananas.
As a longtime celiac sufferer, it would be in my best interest and that of my descendants for all of those varieties to be eradicated, like smallpox. There’s nothing especially beneficial about wheat as a food, and it has drawbacks, such as how it is the only food I can think of with its own autoimmune disease.
I can't say I support your desire to eradicate wheat. I love bread, and without bread probably half the human population would starve. Most of the rest would likely die in the resulting upheaval.
There was a scifi story about such a scenario, I think it was entitled "No Blade of Grass" by John Christopher.
No, wheat is not crucial in a way that people would starve if it were not available. There are dozens of other foods that could be grown which would provide equivalent nutritional benefit. It is not a unique or particularly advantageous source of any nutrition. It does not have any unique advantageous growing properties.
Additionally, while many people are not familiar with cereal grains other than the close wheat family, there is really nothing that different about their flavor or how they taste in cooking. The only useful, unique thing about wheat is that the protein provides a texture in baked goods and sauces that people find pleasant. When forced to explore alternative grains for a couple of years, and having eaten my mothers alternative grain cooking before that, I learned that the gluten-free foods often actually taste better. Wheat is necessary and flavorful like Windows is user friendly and required for your computer to function.
If you put my comment in context, I am not intending to advocate any sort of eradication program for wheat. I’m responding with mild hyperbole to the notion that it is particularly critical to preserve wheat. The main idea that I am promoting here is that there’s nothing special about wheat, other than that it is particularly harmful to some people.
I like bread. I like wheat noodles.
As a child I was allergic to all dairy products with serious eczema from head to toe, even a drop of dairy would initiate it, entire body covered in scabs, arms in wet bandage inner-wrapping, dry outer bangage should I get exposed to even a little milk product. Yet I do not want all dairy products to be banned, they bring valuable nutrition to diverse groups of people, I was just unlucky, but very lucky to be born in a country with a health service that cares.
Wheat is a wonderful food, extremely nutritious, that has been the cornerstone of the development of multiple civilisations.
Why eradicate it? Just avoid it.
Wheat is not wonderfully nutritious. It provides nothing special and is even somewhat problematic.
If the global food industry was capable of keeping wheat out of their food, that would be fantastic. Unlike dairy, almost all dry foods are contaminated with gluten unless you go to lengths to obtain food that is not.
You're speaking from the perspective of someone who always has enough to eat, so you have the privilege of optimizing for nutrient ratios. Billions of other people aren't so lucky, and they just need more calories period. Wheat is great that, along with rice, soybeans, and other staple crops that are better in the growing/volume sense than in the nutritional sense. Not all of humanity can afford boutique heirloom artisanal hand-grown crops that are $10 per pound.
If we're going to optimize for anything, it's for feeding as many people as possible -- there are far fewer celiac sufferers than there are people who go without enough food. Optimizing the food chain to protect you would result in many more people dying from starvation, because you'd be eliminating an efficient, widely grown crop that feeds many. Wheat is the second most important crop in the world, behind only rice.
Actually, I’m speaking from the perspective of someone who is dying from starvation despite being surrounded by available food.
There is nothing special about wheat. All of the resources spent on growing wheat could be expended on many other crops which would provide equal or greater nutritional benefit. The reason wheat is a globally important crop is simply because people have made it that way for arbitrary reasons, like raising European cattle in North America.
I'd like to hear about a food that isn't in some way problematic, can you list any?
The problems I am referring to are celiac and non-celiac gluten sensitivity. There are at least a dozen other grains that provide the benefits of wheat without those disadvantages, and that is to what I am referring. Rice, corn, sorghum, buckwheat, millet, teff, quinoa, lentils, and and so on.
So the "even somewhat problematic" part of wheat is problematic to only 1% of the entire population and that's an argument to kill off all wheat, yeah, no, try again.
The article says wheat has 5x the human genome. I assume that means it’s very high in protein. Isn’t that what most of the world needs, as opposed to mostly carbohydrates?
High in protein compared to what? Is wheat better than millet, sorghum, quinoa, teff, oats, corn, and rice, or is it just a European tradition to base cuisine on wheat? I’m not an agricultural or genetic expert and I have no idea what relation genome complexity has to proteins or how that makes it useful to humans. Overall wheat is not very high in protein... it’s a crop grown for carbohydrates. If you were trying to fulfill your daily protein needs from wheat, you’d fall quite short. I suppose it complements more adequate sources. The protein it does have - gluten - isn’t especially digestible compared to alternatives like corn or rice, though it does have a texture that people find pleasant or useful in baking. Crops like lentils and soy are what you grow if you want to grow protein.
Wheat has a decent protein-to-carbohydrate ratio and you can make seitan from it, which is a great alternative to tofu / tempeh and other legume-based protein sources.
Sure, seitan (aka wheat gluten) is a protein source. How many other grains have a decent protein to carbohydrate ratio though, and are more easily digestible, and don’t cause crippling autoimmune disease or digestive dysfunction in 1-5% of people? You can get concentrated protein from any grain with similar nutritional benefits.
Personally, my sensitivity to gluten has just about ruined my life - right now, my life is on hold and I am staying in a hotel in Rochester while obtaining treatment from the Mayo Clinic’s celiac specialists. Not sure that anyone can say that about quinoa or millet.
no, it means nothing of that sort, it just means the DNA is five times longer, not that there are five time as many genes encoding five times as many proteins. It is more like there is more DNA padding around the genes as a protection from virus which tend to jump limited distances along a genome.
sorry for leading with a negative, I know it can come across more strongly than I intend.
There's a drastically cheaper option for that:
https://en.wikipedia.org/wiki/Gene_bank
e.g.
https://en.wikipedia.org/wiki/Seed_bank
But less reliable. Wasn't one of the seed banks in the arctic destroyed by flooding recently?
Digital versions can be replicated and distributed at 0 cost.
Assuming you're referring to the Svalbard Global Seed Vault, the Wikipedia page answers your question:
> In October 2016, the seed vault experienced an unusually large degree of water intrusion due to higher than average temperatures and heavy rainfall .... The vault was designed for water intrusion and as such the seeds were not at risk.
The article's source: https://www.popsci.com/seed-vault-flooding
Thanks for the reference.
We should indeed continue with seed vaults. But I'd feel better with a backup for that in the form of digital data.
If things go far enough downhill that the Svalbard vault is lost and its contents just allowed to rot, I’d be surprised if we retained the technological capacity to do things like synthesizing a complex genome from data. (I’m not sure we could do that with present technology either, for that matter.)
Libraries and museums burn down all the time, or get destroyed in wars. Consider the recent fire at the Hewlett-Packard museum, where all the paper history was lost. Nobody made a backup, even though paper lasts longer term than data on a hard drive.
Frankly, I think storing data as ASCII in pits on a substrate is a great long term solution, as it can be read with a simple optical microscope, and ASCII is forever.
One of the cool things about digital data is it can be copied forward limitlessly. Make the seed genomes public domain and put them on a server - people will make copies, like they make copies of wikipedia to store in their prepper bunkers.
I think UTF-8 is fine in this case since it's ASCII until it's not so you can write the UTF-8 spec out first.
Human knowledge is more then English alphabet characters and not all concepts translate properly.
Even with the digital copy of the genome, you have to synthesize the entire genome, the cell it belongs in, and the rest of the seed to get a plant. That seems... possible, but hard enough that it doesn't make sense to call the sequenced genome a "backup".
It's infinitely better than having a photo of a wheat stalk.
Is it possible to recreate a wheat plant from just its genome?
No. You need a wheat cell as well. Then you might be in business.
And, no, it is not possible (today) to rebuild a multi gigabase hexaploid genome. The best that's been done so far is mycoplasma (500kb genome, which is many orders of magnitude smaller).
Also, the "genome sequence" presented here is not really complete. Thus far only the simplest organisms have had their genomes synthesized from a digital template and resulted in a viable cell. We rarely can produce a "complete" genome for anything other than bacteria and viruses. And for those, the diversity in the population makes the idea of establishing a single genome sequence somewhat limiting.
Today? No. Likely the so-called "junk DNA" was skipped over and we are still learning what the impact of environment and hormones is on gene expression.
What we can do today is to manipulate DNA and re-inject into an egg. Although not nothing, this is not "just its genome."
In 100 years? Probably.
A decent analogy might be:
is it possible to recreate a running program from just it's source?
(lacking a compiler, development and production environments, and perhaps user inputs)
so my feeling is, not really, to an approximation
Sure it's possible. (I've recreated programs from source despite lacking the compiler, etc., originally used on it. The trick is to adapt something else to the task.) The source contains instructions on how it works, and those instructions can be used elsewhere.