4 ms·

The weird thing is that some of these lncRNA don’t seem to be under super strong selection pressure, at least at the level of individual nucleotides. Their prom

The weird thing is that some of these lncRNA don’t seem to be under super strong selection pressure, at least at the level of individual nucleotides. Their promoter regions are conserved, which indicates that the cell really does need to produce them, but it doesn’t seem to care much the actual sequence. Very strange. Anyways there definitely are non-coding regions that just don’t do much and evolve neutrally. I’m hesitant to call them junk but only because that designation has burned biologists so many times.

_qua 2y ago
I think we’re basically on the same page. As you note, a conserved promoter without strong sequence conservation elsewhere suggests functions that might be more structural or regulatory. Still, it’s also true that some (actually many) non-coding regions show no evidence of selection and appear to evolve neutrally. To borrow an example: an onion likely doesn’t need 5x more DNA than a human, and a lungfish probably doesn’t need 30 times more than we do (and 350x more than a pufferfish). And yet, these enormous genomes exist. It’s very likely that portions of these sequences are what we’d call “junk,” i.e., DNA that doesn’t confer a meaningful functional advantage and can accumulate due to the relatively low cost of carrying it along. If we want to avoid the term “junk,” we could say something like “areas of the genome for which we assign a very low prior probability of functional importance.” But “junk” is a concise shorthand to acknowledge that, while some non-coding sequences matter, there are also huge swaths of DNA in many eukaryotes that show no signs of being anything other than evolutionary baggage.
- robwwilliams 2y ago
  Great overview. Worth adding some population genetics: Multicellular organisms typically have small effective population sizes and reproduce slowly in comparison to bacteria. Selection has a hard time “getting a grip” on variants with very weak effects on fitness. Drift becomes much more important. Bacteria have high population sizes. Selection can be quick and brutal. Low levels of “code of unknown function” in bacteria is perhaps related to replicative efficiency. Fast DNA replication is highly advantageous in nutrient-rich environments. No space (or time) for junk DNA.
kjkjadksj 2y ago
Sometimes with lncrnas the structure is what is more important than sequence. You can have two lncrna with different sequence but the same kmer structure. This makes logical sense as while proteins often bind to specific sequence the reasons for that are merely structural. In protein you can also have conservative missense mutations that are tolerated as binding affinities may not have changed swapping out an amino acid residue for another with the same charge or polar properties. https://pmc.ncbi.nlm.nih.gov/articles/PMC6262761/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6262761/

_qua 2y ago

I think we’re basically on the same page. As you note, a conserved promoter without strong sequence conservation elsewhere suggests functions that might be more structural or regulatory. Still, it’s also true that some (actually many) non-coding regions show no evidence of selection and appear to evolve neutrally. To borrow an example: an onion likely doesn’t need 5x more DNA than a human, and a lungfish probably doesn’t need 30 times more than we do (and 350x more than a pufferfish). And yet, these enormous genomes exist. It’s very likely that portions of these sequences are what we’d call “junk,” i.e., DNA that doesn’t confer a meaningful functional advantage and can accumulate due to the relatively low cost of carrying it along. If we want to avoid the term “junk,” we could say something like “areas of the genome for which we assign a very low prior probability of functional importance.” But “junk” is a concise shorthand to acknowledge that, while some non-coding sequences matter, there are also huge swaths of DNA in many eukaryotes that show no signs of being anything other than evolutionary baggage.

robwwilliams 2y ago
Great overview. Worth adding some population genetics: Multicellular organisms typically have small effective population sizes and reproduce slowly in comparison to bacteria. Selection has a hard time “getting a grip” on variants with very weak effects on fitness. Drift becomes much more important. Bacteria have high population sizes. Selection can be quick and brutal. Low levels of “code of unknown function” in bacteria is perhaps related to replicative efficiency. Fast DNA replication is highly advantageous in nutrient-rich environments. No space (or time) for junk DNA.

kjkjadksj 2y ago

Sometimes with lncrnas the structure is what is more important than sequence. You can have two lncrna with different sequence but the same kmer structure. This makes logical sense as while proteins often bind to specific sequence the reasons for that are merely structural. In protein you can also have conservative missense mutations that are tolerated as binding affinities may not have changed swapping out an amino acid residue for another with the same charge or polar properties. https://pmc.ncbi.nlm.nih.gov/articles/PMC6262761/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6262761/