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Gene location is extremely consequential, especially in Eukaryotes (everything that's not bacteria or bugs living near hydrothemal vents). A couple of things th

Gene location is extremely consequential, especially in Eukaryotes (everything that's not bacteria or bugs living near hydrothemal vents). A couple of things that are influenced by position: * First, and most immediate, are promoter/suppressor sequences. These are the bits of non-coding DNA that regulate when a gene is turned on or off. If you move a gene away from its promoter, it will not turn on and off at the right times. These sequences are so closely tied to the proper functioning of a "gene" (typically a term that refers to the introns and exons of a coding sequence), that the operating definition of "gene" should probably be expanded to include them. * Copy number. Chromosomes take a long time to copy, and if you had to copy the whole length of a chromosome from one end to the other you'd never get a chance to divide. So chromosomes contain multiple ORIs (origin of replication). Even so, it takes long enough to copy DNA that genes located near an ORI will have an effective gene dose higher than those located further away (i.e. it will be almost as if you have two copies of the genes close to an ORI and only one copy for those further away). Granted this effect is more pronounced in bacteria with circular chromosomes and a single ORI, where gene dose can differ by a factor of 4 (or even 8) depending on location, but the effect is still there. * Sub-nuclear localization. This is an area that is still under active study (last I cared to look...which is a number of years ago now), but there does seem to be some order to the location of chromosomes within the nucleus during interphase (i.e. when the cell is not compacting chromosomes and lining them up to split the cell). It's likely that this localization is related to the distribution of various signaling pathways so that, if a gene is expecting to be "turned on" by a specific pathway, but it happens to become dislocated in the nucleus from where the elements of that pathway are doing the work of activating genes, then it may not respond the same way to extrinsic signaling. * Finally, and most importantly: heterochromatin/epigenetics. In addition to regulation that occurs on a gene-by-gene basis, eukaryotes are also capable of large-scale regional regulation of their chromosomes. Essentially, a signal causes modification of the histones associated with a region of DNA and the entire region becomes "condensed" into heterochromatin. A gene in a heterochromatin region will not become activated even if all of the signals that would normally kick it into gear are going full blast. In other words, if you accidentally move a gene that should be active into a region of heterochromatin, you may as well have removed it from the cell entirely!

dnautics 7y ago
I'm going to go against this and say no. We swap gene locations, all the time wholesale in mice, and usually the effect is limited. That doesn't get you a paper, so of course you publish when something... more interesting crops up. It's just that there are many well-studied systems where where there are profound and severe effects that are singly extremely consequential, where you go "huh, wouldn't have guessed that" and the cause turns out to be really subtle. If we're going with eukarya writ large, it's even less. Basically entire programs of plant husbandry is the industrial process of performing chromosomal translocation and overloading, and picking the one out a thousand? ten thousand? that reveals a commercially useful variant. And yeast, well we've sliced and diced those chromosomes like no one's business (but it turns out they are particularly robust). I would go so far to say as "the general rule is that chromosomal location doesn't matter in yeast, with a handful of exceptions". Conversely, there is one gene whose chromosomal location is basically invariant in prokarya, that's dnaA, which pretty much "has to be close to the ori".
- jballanc 7y ago
  So, two quick points in response: 1. Yeah, I probably overstated the case. It's not as if it's impossible to move a gene somewhere else on a chromosome and have it function completely normally. As you point out, we do this all the time. That said... 2. Genetics is hard, and I'm of the school of thought that one reason it is so hard is because systems are more fragile in meaningful ways than we assume. That is to say, if you attempt a gene translocation 100 times and get 3 successes, most geneticists would be happy with that result and not question the 97 failures. And, indeed, it is entirely possible that the quality of the reagents, the stringency of the protocols, or any of an infinite number of other variables that have little or nothing to do with genetics could be the cause of those 97 failures...or, it could be that 97 times the translocation worked but the product wasn't viable. I know from experience that it is very hard to distinguish between these possibilities, and furthermore that in the publish-or-perish world of academia today there's not any motivation for navel gazing into the reason most genetic protocols are not more efficient. That said, I've seen hints in my past work that make me think location, gene dose, DNA secondary and tertiary structure, etc. are more consequential than the common wisdom would have you believe. (Oh, and for anyone still reading, I'll share the brain teaser that was my light-bulb moment for the extent of gene dose effect in prokarya: it takes 40 min to replicate the E. coli genome, but during exponential growth E. coli can double in number every 20 min. How?)

dnautics 7y ago

I'm going to go against this and say no. We swap gene locations, all the time wholesale in mice, and usually the effect is limited. That doesn't get you a paper, so of course you publish when something... more interesting crops up. It's just that there are many well-studied systems where where there are profound and severe effects that are singly extremely consequential, where you go "huh, wouldn't have guessed that" and the cause turns out to be really subtle. If we're going with eukarya writ large, it's even less. Basically entire programs of plant husbandry is the industrial process of performing chromosomal translocation and overloading, and picking the one out a thousand? ten thousand? that reveals a commercially useful variant. And yeast, well we've sliced and diced those chromosomes like no one's business (but it turns out they are particularly robust). I would go so far to say as "the general rule is that chromosomal location doesn't matter in yeast, with a handful of exceptions". Conversely, there is one gene whose chromosomal location is basically invariant in prokarya, that's dnaA, which pretty much "has to be close to the ori".

jballanc 7y ago
So, two quick points in response: 1. Yeah, I probably overstated the case. It's not as if it's impossible to move a gene somewhere else on a chromosome and have it function completely normally. As you point out, we do this all the time. That said... 2. Genetics is hard, and I'm of the school of thought that one reason it is so hard is because systems are more fragile in meaningful ways than we assume. That is to say, if you attempt a gene translocation 100 times and get 3 successes, most geneticists would be happy with that result and not question the 97 failures. And, indeed, it is entirely possible that the quality of the reagents, the stringency of the protocols, or any of an infinite number of other variables that have little or nothing to do with genetics could be the cause of those 97 failures...or, it could be that 97 times the translocation worked but the product wasn't viable. I know from experience that it is very hard to distinguish between these possibilities, and furthermore that in the publish-or-perish world of academia today there's not any motivation for navel gazing into the reason most genetic protocols are not more efficient. That said, I've seen hints in my past work that make me think location, gene dose, DNA secondary and tertiary structure, etc. are more consequential than the common wisdom would have you believe. (Oh, and for anyone still reading, I'll share the brain teaser that was my light-bulb moment for the extent of gene dose effect in prokarya: it takes 40 min to replicate the E. coli genome, but during exponential growth E. coli can double in number every 20 min. How?)