A Quarter of Cow DNA Came from Reptiles(theatlantic.com)
theatlantic.com
A Quarter of Cow DNA Came from Reptiles
https://www.theatlantic.com/science/archive/2017/10/how-a-quarter-of-the-cow-genome-came-from-reptiles/542868/?single_page=true
43 comments
> I think some people may have the idea that we can observe whole genomes easily
I think a lot of people do. Certainly I did, before I spent a year working in a genomics institute and had the opportunity for close observation of the massive uncertainty produced by short reads, and the concomitant complexity of the methods required to develop useful information from them.
At that time, long reads were just beginning to look reasonably attainable with new approached from Pacific Biosciences and other challengers to Illumina's market share; I'd be curious to know whether there's been any major movement in the half decade or so since I returned to industry.
I think a lot of people do. Certainly I did, before I spent a year working in a genomics institute and had the opportunity for close observation of the massive uncertainty produced by short reads, and the concomitant complexity of the methods required to develop useful information from them.
At that time, long reads were just beginning to look reasonably attainable with new approached from Pacific Biosciences and other challengers to Illumina's market share; I'd be curious to know whether there's been any major movement in the half decade or so since I returned to industry.
The biggest development in single-molecule sequencing (aside from the steady improvement in PacBio's methods) is the arrival of the Oxford Nanopore devices on the market. These are also pretty rough around the edges, but they suggest a future in which labs have direct access to long-read, low-cost sequencing. Also, techniques like that from 10X genomics allow large-scale haplotype resolution, which is another missing component of a true "whole genome" sequence (humans and many other creatures have more than one different genome copy).
Its been a few years since I was in genetics, what device currently gives the longest single reads? If I remember right we were getting the best from the Roche 454 and the Illumina HiSeq, but the iontorrent was better at other things.
Probably the nanopore readers, but sometimes the reads get up to 30% wrong, which means you need to get multiple reads anyways to get consensus.
Iontorrent has very short reads (250bp) but I think they have 1kb working at least in the lab.
Iontorrent has very short reads (250bp) but I think they have 1kb working at least in the lab.
Are there any (perhaps prohibitively expensive) techniques that give high fidelity for transposons? This seems like a problem well suited to machine learning, given a dataset of paired high quality and low quality sequence data.
Transposon display
https://www.ncbi.nlm.nih.gov/pubmed/23918433
>I think some people may have the idea that we can observe whole genomes easily
By and large, we can. Yes there are minute aspects which lack perfect resolution, but we are well into the sub-1000 dollar whole-genome age.
Particularly in humans, can get a highly accurate reading of your variation across your entire genome, including insertions and deletions which are even easier to spot.
Of course there is cryptic variation, but it is only in really obscure genetic diseases and complex phenotypes that we start to run into trouble. Both of which can be addressed by simply sequencing a deeper population of individuals.
By and large, we can. Yes there are minute aspects which lack perfect resolution, but we are well into the sub-1000 dollar whole-genome age.
Particularly in humans, can get a highly accurate reading of your variation across your entire genome, including insertions and deletions which are even easier to spot.
Of course there is cryptic variation, but it is only in really obscure genetic diseases and complex phenotypes that we start to run into trouble. Both of which can be addressed by simply sequencing a deeper population of individuals.
> Particularly in humans, can get a highly accurate reading of your variation across your entire genome, including insertions and deletions which are even easier to spot.
Insertions and deletions are usually harder to spot with the short reads that make up the data that you'll get back from your typical "sub-1000 dollar whole genome". The reason is simple. There are vastly more possible insertions and deletions that SNPs, and these all must be considered by algorithms in order to detect them. Worse, as the length of the insertion or deletion increases to a reasonable fraction of the length of your reads, it becomes impossible to hope to resolve the event without considering an untenable space of possible indels and opening yourself to spurious matching.
Those cheap genomes have a serious blind spot--- they don't easily yield information about the large scale variation in structure (indels, copy number, inversions, translocations) that are apparently very important to evolution. I believe the field has blinded itself to the importance of large variation simply because it is hard to observe. Recent papers based on long read data have started to respond to this assumption in a serious way (https://www.biorxiv.org/content/early/2016/09/24/076562).
> Yes there are minute aspects which lack perfect resolution
In the context of humans there is ample evidence that the things we are missing with short reads are not minute, but are rather an enormous elephant in the room, see https://biosci-batzerlab.biology.lsu.edu/Publications/Sudman... and http://science.sciencemag.org/content/349/6253/aab3761. They report that some genomic regions are expanding by up to 50-fold between individuals. Some whole human populations feature quarter-megabase duplications not present in other groups. The scope of the studies are actually very narrow, with hundreds of individuals being considered. I would be surprised if this is anything less than the tip of the iceberg, and incredibly surprised if this turns out to be a minute detail.
Insertions and deletions are usually harder to spot with the short reads that make up the data that you'll get back from your typical "sub-1000 dollar whole genome". The reason is simple. There are vastly more possible insertions and deletions that SNPs, and these all must be considered by algorithms in order to detect them. Worse, as the length of the insertion or deletion increases to a reasonable fraction of the length of your reads, it becomes impossible to hope to resolve the event without considering an untenable space of possible indels and opening yourself to spurious matching.
Those cheap genomes have a serious blind spot--- they don't easily yield information about the large scale variation in structure (indels, copy number, inversions, translocations) that are apparently very important to evolution. I believe the field has blinded itself to the importance of large variation simply because it is hard to observe. Recent papers based on long read data have started to respond to this assumption in a serious way (https://www.biorxiv.org/content/early/2016/09/24/076562).
> Yes there are minute aspects which lack perfect resolution
In the context of humans there is ample evidence that the things we are missing with short reads are not minute, but are rather an enormous elephant in the room, see https://biosci-batzerlab.biology.lsu.edu/Publications/Sudman... and http://science.sciencemag.org/content/349/6253/aab3761. They report that some genomic regions are expanding by up to 50-fold between individuals. Some whole human populations feature quarter-megabase duplications not present in other groups. The scope of the studies are actually very narrow, with hundreds of individuals being considered. I would be surprised if this is anything less than the tip of the iceberg, and incredibly surprised if this turns out to be a minute detail.
Given this shows how easily DNA is acquired from an external source; how do we know certain sequences come from common ancestry rather than by other means?
We've known about horizontal gene transfer for a long time. We do seem to be learning that it's more common than we thought, making species boundaries much more fuzzy and fluid than previously believed.
Common ancestry is probably best understood in aggregate. When we look at genetics in aggregate we see a lot of common sequences that are highly conserved across all of nature.
Edit: also shows why most anti-GMO hysteria is nonsense. Everything is "transgenic." Species are fuzzy.
Common ancestry is probably best understood in aggregate. When we look at genetics in aggregate we see a lot of common sequences that are highly conserved across all of nature.
Edit: also shows why most anti-GMO hysteria is nonsense. Everything is "transgenic." Species are fuzzy.
Monsanto's practices with GMO are problematic, and need to be denounced and made illegal (terminator genes, glyphosate resistant crops, etc...).
GMO per se are IMO a net good, we're increasing biodiversity.
Also, they are crucial in medicine. Insulin and other peptide-derived treatments are synthesized by GMO bacteria and yeasts (see "recombinant DNA").
GMO per se are IMO a net good, we're increasing biodiversity.
Also, they are crucial in medicine. Insulin and other peptide-derived treatments are synthesized by GMO bacteria and yeasts (see "recombinant DNA").
>we're increasing biodiversity
Are you sure? Farmers used to have their own subtly different strains of crops at the individual, village, town, and country levels in a kind of expanding concentric ring pattern. Now, at least for cash crops, it's just a few varieties all "manufactured" by one central power.
Are you sure? Farmers used to have their own subtly different strains of crops at the individual, village, town, and country levels in a kind of expanding concentric ring pattern. Now, at least for cash crops, it's just a few varieties all "manufactured" by one central power.
It is artificial biodiversity. Without the current legal framework (where seeds/genes can be patented), farmers could hybridize GMO with their own crops to add interesting traits to their own strains.
The current uniformity predates GMOs, it stems from F1 hybrids that are effectively clones, and the legislation that makes it practically illegal to sell or plant non-patented seeds.
The current uniformity predates GMOs, it stems from F1 hybrids that are effectively clones, and the legislation that makes it practically illegal to sell or plant non-patented seeds.
>The current uniformity predates GMOs, it stems from F1 hybrids that are effectively clones, and the legislation that makes it practically illegal to sell or plant non-patented seeds.
Granted.
But in the grand scheme of things, this is as equally an astonishingly new situation as is mechanized agriculture. A hundred years ago, most people lived and worked on farms; now it's like 1% or something like that.
I know that Monsanto's shareholders need to make rivers of dosh, boatloads of cash, money hand over fist, but I don't understand how in practice they've managed to get a vice-grip on everybody's family jewels.
Granted.
But in the grand scheme of things, this is as equally an astonishingly new situation as is mechanized agriculture. A hundred years ago, most people lived and worked on farms; now it's like 1% or something like that.
I know that Monsanto's shareholders need to make rivers of dosh, boatloads of cash, money hand over fist, but I don't understand how in practice they've managed to get a vice-grip on everybody's family jewels.
Terminator genes are already not used by Monsanto. https://monsanto.com/company/media/statements/terminator-see...
As for glyphosate resistant crops, beyond the currently insufficient science (lots of invalid studies!), I can't see any reason to denounce it or make it illegal).
As for glyphosate resistant crops, beyond the currently insufficient science (lots of invalid studies!), I can't see any reason to denounce it or make it illegal).
Why should Monsanto's work be illegal? What would be the result of change vs. no change in legality?
So how do we know if a particular sequence is from aggregate effects, sounds like "we don't" [in a rigorous scientific manner] from your answer?
As a layman, the story I've seen up to now is roughly "these sequences are the same, therefore there is a common ancestry"; but this information shows that argument doesn't work on a wide scale across species in this simplistic form -- so either the basis of common ancestry being inferred from similar DNA is not scientific (or is falsified) or we have results that show whence the particular sequences came from (ie there's a more nuanced result)?
In short that answer is unsatisfyingly vague.
As a layman, the story I've seen up to now is roughly "these sequences are the same, therefore there is a common ancestry"; but this information shows that argument doesn't work on a wide scale across species in this simplistic form -- so either the basis of common ancestry being inferred from similar DNA is not scientific (or is falsified) or we have results that show whence the particular sequences came from (ie there's a more nuanced result)?
In short that answer is unsatisfyingly vague.
[deleted]
The problem with GMO foods is not that they have been manually manipulated by man, but that they have been manually manipulated by men with interests not necessarily congruent with the persons eating them: namely, the emphasis of crop yield, appearance, and appealing ("cheap") taste over soil quality, sustainability, nutrition, and general "goodness" — in short, the pursuit of short-term private profit over long-term social good, at the expense of commons which before modern technology were simply practically inviolable.
That's kind of why I said "hysteria." I was thinking of the blanket suspicion of any and all GMO products because they are GMO, not more nuanced thoughts such as yours.
Technologies are just tools. It's all in how they are used.
Technologies are just tools. It's all in how they are used.
Well, all GMO products are subject to the same pressures of divergent interests. If you eat things, and if some GMO products you might eat are bad, and if the only genetic-modification-related insight you have into what you eat is "is-GMO" or "not-GMO", then the (entirely rational and reasonable) heuristic to adopt is an "hysterical" avoidance of GMO products.
Also, the reason why a person does or does not do such a thing is rather of less importance than what that thing is that he does or does not do. For example, if pigs carry disease, and your religion proscribes you from eating pigs because "God says so", your life is preserved whether or not you or anyone else have any conception of germ theory whatever.
Also, the reason why a person does or does not do such a thing is rather of less importance than what that thing is that he does or does not do. For example, if pigs carry disease, and your religion proscribes you from eating pigs because "God says so", your life is preserved whether or not you or anyone else have any conception of germ theory whatever.
Can someone explain a bit more about "horizontal transfer"?
It would seem that a gene is simply a symbol in relation to the DNA it is a part of, and so there is no reason to believe that a particular gene would mean the same thing in two different species DNA.
The context for the meaning of the gene would seemingly be completely accidental. But then if a horizontal transfer resulted (by chance) in something with selection value, it would be likely to remain in the population.
Do horizontally transferred genes typically do something novel? Or do they interact with other (distantly, vertically shared) genes in their resulting expressions?
Is my description of a gene in the context of DNA being a "symbol" accurate? Or is there a more accurate programming metaphor. I would hesitate to liken it to a subroutine, but I am curious if it might be more analogous to a type class or something like that.
It would seem that a gene is simply a symbol in relation to the DNA it is a part of, and so there is no reason to believe that a particular gene would mean the same thing in two different species DNA.
The context for the meaning of the gene would seemingly be completely accidental. But then if a horizontal transfer resulted (by chance) in something with selection value, it would be likely to remain in the population.
Do horizontally transferred genes typically do something novel? Or do they interact with other (distantly, vertically shared) genes in their resulting expressions?
Is my description of a gene in the context of DNA being a "symbol" accurate? Or is there a more accurate programming metaphor. I would hesitate to liken it to a subroutine, but I am curious if it might be more analogous to a type class or something like that.
"Gene" is often used as a technical term to refer to a stretch of DNA that produces a protein. If it's being used that way here (no opinion), then in a pretty raw sense it would mean exactly the same thing in two different species. Specifically, it would mean that both species produced e.g. lactase.
The overwhelming majority of DNA is not "genes" in this sense, which confuses a ton of people.
The overwhelming majority of DNA is not "genes" in this sense, which confuses a ton of people.
> Gene" is often used as a technical term to refer to a stretch of DNA that produces a protein.
How does something like pleiotropy happen if a gene simply codes for a protein? Is the thing that is pleiotropic actually the protein?
How does something like pleiotropy happen if a gene simply codes for a protein? Is the thing that is pleiotropic actually the protein?
Well, in the first place, I think my original comment was pretty clear that the word "gene" is used in multiple senses. For example, the words immediately following your quote are "if it's being used that way here...".
In the much less important second place, it shouldn't be hard to imagine that two different phenotypical processes might both be cued by the presence of the same chemical.
In the much less important second place, it shouldn't be hard to imagine that two different phenotypical processes might both be cued by the presence of the same chemical.
The ontology of genetics is not isomorphc with the actual physical methods by which phenotypes are expressed. Think of genetics (and the content that a gene codes for proteins) as a first order approximation to the actual underlying mechanics, or as the primary component in a multidimensional, nonlinear, feedback driven system.
Not a biologist.
Most genes code for proteins, so in a programming sense, the genome would be a directory and the genes files. Obviously, the raw order and position of files on disk doesn't matter if you just want to run them.
But it seems that there is also information in the genome which is position dependent, which is more of what you alluded, that moving stuff around would break things.
Most genes code for proteins, so in a programming sense, the genome would be a directory and the genes files. Obviously, the raw order and position of files on disk doesn't matter if you just want to run them.
But it seems that there is also information in the genome which is position dependent, which is more of what you alluded, that moving stuff around would break things.
Or, like any good programmer, when God was coding animal DNA:
#include <BovB.h>
#include <BovB.h>
God would not use an imperative language.
p.s.
Look, imperative is most of what I've done and ~understand. I am not making it out to be inferior, rather questioning fitness for the job. Time and Place peekaboo thinking just seems pedastrian for a transcendent entity devising a world. (That's even an inside joke in Genesis with God looking for Adam.) Short scripting of little bits, sure, but blueprints and stuff, no way.
But, yes, this is just an opinion.
p.s.
Look, imperative is most of what I've done and ~understand. I am not making it out to be inferior, rather questioning fitness for the job. Time and Place peekaboo thinking just seems pedastrian for a transcendent entity devising a world. (That's even an inside joke in Genesis with God looking for Adam.) Short scripting of little bits, sure, but blueprints and stuff, no way.
But, yes, this is just an opinion.
Yeah, but apparently he forgot to guard his header with:
#ifndef __BOV_B_H__
#define __BOV_B_H__
#endif
#ifndef __BOV_B_H__
#define __BOV_B_H__
#endif
He certainly didn't forget it. He is a good programmer after all.
The entire problem is that he left an extra underline at the end of the #define, and 3 underlines look exactly like 2.
The entire problem is that he left an extra underline at the end of the #define, and 3 underlines look exactly like 2.
The bovine DNA has around 22,000 genes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200/
The claim that 5,500 of those are in common with reptiles is unsubstantiated. The claim that they came directly from reptiles and not from a common ancestor is absurd.
The claim that 5,500 of those are in common with reptiles is unsubstantiated. The claim that they came directly from reptiles and not from a common ancestor is absurd.
I think some people may have the idea that we can observe whole genomes easily, but consider the case of repeats like transposons. Half of the human genome is made up of these, but we still have trouble seeing when and where they are active. A new insertion of a big piece of DNA can be much more phenotypically effective than a little SNP, and yet our observational methods make the latter much easier to see than the first. It seems that structural variation in genomes is a likely place to find at least a partial solution to the missing heritability problem posed by the GWAS community.
https://en.wikipedia.org/wiki/Missing_heritability_problem