6 ms·

How Many Genes Do Cells Need? Maybe Almost All of Them

35 points by digital55 9y ago

dddddaviddddd 9y ago
In bacteria at least it's well-established that natural selection favours a smaller genome -- hence why antibiotic resistance will be dropped if the selective pressure is removed.
- danieltillett 9y ago
  Unfortunately, it is not dropped completely, just reduced in the bacterial population. It would seem a simple idea to just rotate antibiotics (use for a few years then put on the shelf for a few years), but once a bacterial pathogen acquires resistance it never really loses it and once you start using the the antibiotic again the resistance roars back very quickly.
mxwsn 9y ago
This line of thinking really highlights how building models that predict phenotype from genotype assuming linear and independent genetic contributions, though useful for predicting something like height [0] [1], is not going to generalize sufficiently to solve the lofty goal of personalized precision medicine even with an explosion in data. Biologically, we know tons and tons about the interconnected biochemical pathways that cause a lot of activity in the cell. It's impressive that statistical modeling approaches that ignore this knowledge earned by thousands of humanyears worth of work can work so well in some domains, but I'm wary of the possibility of academic communities isolating themselves from empiricism and continuing to make mathematically-convenient assumptions, which in the long-run helps no one but themselves. [0] https://news.ycombinator.com/item?id=16392877 https://news.ycombinator.com/item?id=16392877 [1] https://www.biorxiv.org/content/early/2017/09/19/190124 https://www.biorxiv.org/content/early/2017/09/19/190124
- carbocation 9y ago
  I don't think this is ignored by the scientific community at all. For example, Eric Lander's group has a pretty nice treatment of why additive models can't explain heritability [1]. And this is coming from the same Eric Lander who has done some of the key work in complex disease / additive genetic modeling. Imagine you're in a world where you are handed down some knowledge there are Newtonian models, and more advanced models that use relativity, but you don't know what the constants are yet. We're still looking for the Newtonian constants. We know there is much more out there once we understand the basics. But the basics are still worth understanding. 1 = http://www.pnas.org/content/109/4/1193 http://www.pnas.org/content/109/4/1193
derefr 9y ago
Hypothesis: it’s not so much the content of the genes that’s brittle, as that there are very few proteins as “smart” in how they walk the genome as CRISPR is (and even it’s no Einstein.) There are likely cellular genetic repair mechanisms—especially in “small” genebases that don’t use fancy tricks like methylation/acetylation—which “hardcode” assumptions about gene number, gene size, positions of important proteins, etc. Just because DNA itself is a robust data-structure (with features like start-stop tags, commented sections, etc.) doesn’t mean that all the algorithms (proteins) that have evolved to utilize that data-structure query or mutate it in equally-robust ways. Imagine a codebase started off by a brilliant and strict engineer... and then followed on by a million forks-of-forks-of-forks, all done by average Joes just “scratching their own itch.” That’s the type of software encoded in 99% of the DNA on Earth. The codebases where “every line counts” and has been carefully selected for are far fewer—mitochondria, certainly, but i hesitate to name any other clear candidate.
- ynonym00s 9y ago
  Would you mind explaining what you mean by 'commented sections' in DNA? I have a very basic understanding of DNA.
  - atrexler 9y ago
    The proteins that organize DNA, called histones, can be chemically modified in a variety of ways. The modifications have the effect of turning on/off stretches of the DNA simply by modifying its physical structure (the way the dna is arranged and packed around the histones). There are tons more mods that can happen which have a variety of effects (for example, tune the amount that a gene is expressed). This is called epigenetics if you want to google more. If you've heard of those studies where if your grandparents experienced a famine it makes some difference in your genetics, one hypothesis is that its caused by this.
    - nonbel 9y ago
      This doesn't sound "commented" at all. It sounds like you are talking about conditional statements/loops.
callesgg 9y ago
What definition of gene are they using is this article?
- IAmEveryone 9y ago
  The same as everyone, I. e. a protein-coding segment of DNA?
  - callesgg 9y ago
    No that is not true, there are genes that does not contain protin coding segments. There is no clear definition where a gene starts and ends. Some define it as a segment that codes for a specific feature but that is a recursive definition. Here is an article about what I mean: https://www.gmwatch.org/en/news/archive/2000/8975-genetic-determinism-is-dead-theres-no-such-thing-as-a-gene-27122000 https://www.gmwatch.org/en/news/archive/2000/8975-genetic-de...

35 points by digital55 9y ago

In bacteria at least it's well-established that natural selection favours a smaller genome -- hence why antibiotic resistance will be dropped if the selective pressure is removed.

danieltillett 9y ago
Unfortunately, it is not dropped completely, just reduced in the bacterial population. It would seem a simple idea to just rotate antibiotics (use for a few years then put on the shelf for a few years), but once a bacterial pathogen acquires resistance it never really loses it and once you start using the the antibiotic again the resistance roars back very quickly.

mxwsn 9y ago

This line of thinking really highlights how building models that predict phenotype from genotype assuming linear and independent genetic contributions, though useful for predicting something like height [0] [1], is not going to generalize sufficiently to solve the lofty goal of personalized precision medicine even with an explosion in data. Biologically, we know tons and tons about the interconnected biochemical pathways that cause a lot of activity in the cell. It's impressive that statistical modeling approaches that ignore this knowledge earned by thousands of humanyears worth of work can work so well in some domains, but I'm wary of the possibility of academic communities isolating themselves from empiricism and continuing to make mathematically-convenient assumptions, which in the long-run helps no one but themselves. [0] https://news.ycombinator.com/item?id=16392877 https://news.ycombinator.com/item?id=16392877 [1] https://www.biorxiv.org/content/early/2017/09/19/190124 https://www.biorxiv.org/content/early/2017/09/19/190124

carbocation 9y ago
I don't think this is ignored by the scientific community at all. For example, Eric Lander's group has a pretty nice treatment of why additive models can't explain heritability [1]. And this is coming from the same Eric Lander who has done some of the key work in complex disease / additive genetic modeling. Imagine you're in a world where you are handed down some knowledge there are Newtonian models, and more advanced models that use relativity, but you don't know what the constants are yet. We're still looking for the Newtonian constants. We know there is much more out there once we understand the basics. But the basics are still worth understanding. 1 = http://www.pnas.org/content/109/4/1193 http://www.pnas.org/content/109/4/1193

derefr 9y ago

Hypothesis: it’s not so much the content of the genes that’s brittle, as that there are very few proteins as “smart” in how they walk the genome as CRISPR is (and even it’s no Einstein.) There are likely cellular genetic repair mechanisms—especially in “small” genebases that don’t use fancy tricks like methylation/acetylation—which “hardcode” assumptions about gene number, gene size, positions of important proteins, etc. Just because DNA itself is a robust data-structure (with features like start-stop tags, commented sections, etc.) doesn’t mean that all the algorithms (proteins) that have evolved to utilize that data-structure query or mutate it in equally-robust ways. Imagine a codebase started off by a brilliant and strict engineer... and then followed on by a million forks-of-forks-of-forks, all done by average Joes just “scratching their own itch.” That’s the type of software encoded in 99% of the DNA on Earth. The codebases where “every line counts” and has been carefully selected for are far fewer—mitochondria, certainly, but i hesitate to name any other clear candidate.

ynonym00s 9y ago
Would you mind explaining what you mean by 'commented sections' in DNA? I have a very basic understanding of DNA.
- atrexler 9y ago
  The proteins that organize DNA, called histones, can be chemically modified in a variety of ways. The modifications have the effect of turning on/off stretches of the DNA simply by modifying its physical structure (the way the dna is arranged and packed around the histones). There are tons more mods that can happen which have a variety of effects (for example, tune the amount that a gene is expressed). This is called epigenetics if you want to google more. If you've heard of those studies where if your grandparents experienced a famine it makes some difference in your genetics, one hypothesis is that its caused by this.
  - nonbel 9y ago
    This doesn't sound "commented" at all. It sounds like you are talking about conditional statements/loops.

callesgg 9y ago

What definition of gene are they using is this article?

IAmEveryone 9y ago
The same as everyone, I. e. a protein-coding segment of DNA?
- callesgg 9y ago
  No that is not true, there are genes that does not contain protin coding segments. There is no clear definition where a gene starts and ends. Some define it as a segment that codes for a specific feature but that is a recursive definition. Here is an article about what I mean: https://www.gmwatch.org/en/news/archive/2000/8975-genetic-determinism-is-dead-theres-no-such-thing-as-a-gene-27122000 https://www.gmwatch.org/en/news/archive/2000/8975-genetic-de...