3 ms·

Question from the peanut gallery: if you were to flip a single bit in this junk DNA, are the outcomes only slightly different or could they be wildly variable d

Question from the peanut gallery: if you were to flip a single bit in this junk DNA, are the outcomes only slightly different or could they be wildly variable depending on which bit was flipped?

axg11 5y ago
Wildly variable. That’s true for all DNA including protein coding DNA. It’s much more likely that changing a base in a protein coding region will result in an effect, but still nowhere near guaranteed. Statistically, the average human has ~1 base variant (SNP) in a protein coding region somewhere in their genome. In almost all people the effect of that SNP is no more apparent than the effect of SNPs in “junk DNA”.
- robwwilliams 5y ago
  Not true at all. So much charming and well intentioned misinformation on this thread; as much as if I were to weigh in on the pros and cons of MariaBD versus PostgreSL. Coding sequence is under significantly higher levels of active “purifying” selection than regulatory DNA, and much higher than de novo mutations in repetitive mobile elements that only rare perturb phenotypes.
  - axg11 5y ago
    Single point mutations in regulatory elements such as enhancers have been shown to change the expression levels of multiple genes. These elements are under just as much selective pressure as any coding region.
    - asdff 5y ago
      not all noncoding dna is going to be a regulatory element.
- sterlind 5y ago
  what do you mean by "~1 SNP?" one de novo amino acid substitution? or inherited? we have millions of variants. the redundancy of codons - several codons code for most amino acids, and one-base-pair changes are often synonymous or will code for similarly-charged residues - provides some protection. on the other hand, if you have a mutation in, say, a non-coding intronic splice site, that can really fuck a protein up. I got unlucky there.
haihaibye 5y ago
You can't change 1 bit, each base contains 2 bits of information. We can compare each base vs ancestor bases, eg primates and other vertebrates - called conservation scores. Some areas are highly conserved, so changing those will probably have worse outcomes than less conserved regions.

Question from the peanut gallery: if you were to flip a single bit in this junk DNA, are the outcomes only slightly different or could they be wildly variable depending on which bit was flipped?

axg11 5y ago

Wildly variable. That’s true for all DNA including protein coding DNA. It’s much more likely that changing a base in a protein coding region will result in an effect, but still nowhere near guaranteed. Statistically, the average human has ~1 base variant (SNP) in a protein coding region somewhere in their genome. In almost all people the effect of that SNP is no more apparent than the effect of SNPs in “junk DNA”.

robwwilliams 5y ago
Not true at all. So much charming and well intentioned misinformation on this thread; as much as if I were to weigh in on the pros and cons of MariaBD versus PostgreSL. Coding sequence is under significantly higher levels of active “purifying” selection than regulatory DNA, and much higher than de novo mutations in repetitive mobile elements that only rare perturb phenotypes.
- axg11 5y ago
  Single point mutations in regulatory elements such as enhancers have been shown to change the expression levels of multiple genes. These elements are under just as much selective pressure as any coding region.
  - asdff 5y ago
    not all noncoding dna is going to be a regulatory element.
sterlind 5y ago
what do you mean by "~1 SNP?" one de novo amino acid substitution? or inherited? we have millions of variants. the redundancy of codons - several codons code for most amino acids, and one-base-pair changes are often synonymous or will code for similarly-charged residues - provides some protection. on the other hand, if you have a mutation in, say, a non-coding intronic splice site, that can really fuck a protein up. I got unlucky there.

haihaibye 5y ago

You can't change 1 bit, each base contains 2 bits of information. We can compare each base vs ancestor bases, eg primates and other vertebrates - called conservation scores. Some areas are highly conserved, so changing those will probably have worse outcomes than less conserved regions.