PMC:5118421 / 28839-30447 JSONTXT

{"project":"TEST0","denotations":[{"id":"27920779-179-184-3100255","span":{"begin":179,"end":180},"obj":"[\"20805563\"]"},{"id":"27920779-182-187-3100256","span":{"begin":182,"end":183},"obj":"[\"8011289\"]"},{"id":"27920779-193-199-3100257","span":{"begin":529,"end":531},"obj":"[\"7651532\"]"},{"id":"27920779-229-235-3100258","span":{"begin":1526,"end":1528},"obj":"[\"11859119\"]"}],"text":"AGY Ser codons are potentially dangerous because they easily mutate to generate Arg codons with an associated potential to impart antinuclear activity to the respective antibody (1, 3). This raises a paradox because TCN Ser codons do not have this propensity and yet are far less abundant in Ab V region genes and specifically in CDRs. Wagner and colleagues originally hypothesized that this bias toward AGY Ser codons in CDRs was due to a selection pressure to constrain AID motifs to Ag-binding regions of the B cell receptor (17). While this is plausible, our data reveal that this explanation alone cannot account for CDR AGY codon abundance because CDR AGY triplets occur predominantly in the Ser reading frame, even though AID is blind to the translational reading frame. Because TCA and TCG can mutate to stop codons by single-base changes, it is plausible that high CDR AGY/TCN ratios are due in part to selection against these codons. This may hold for TCG which had a low observed/expected ratio, but apparently not for TCA, which had an observed/expected ratio of greater than one, even though it can mutate to a stop codon by two different single-base changes. Overall the observed/expected ratios for TCN codons were greater than one in CDRs. Finally, if there was selection pressure against TCN due to the stop codon potential, we would expect that TCN would be underrepresented in CDRs relative to FRs because there is a bias for increased mutation in CDRs that cannot be explained solely by triplet sequences (13). However no such bias was seen for the Vκ genes of either species (Figure 1A)."}

{"project":"2_test","denotations":[{"id":"27920779-20805563-34707978","span":{"begin":179,"end":180},"obj":"20805563"},{"id":"27920779-8011289-34707979","span":{"begin":182,"end":183},"obj":"8011289"},{"id":"27920779-7651532-34707980","span":{"begin":529,"end":531},"obj":"7651532"},{"id":"27920779-11859119-34707981","span":{"begin":1526,"end":1528},"obj":"11859119"}],"text":"AGY Ser codons are potentially dangerous because they easily mutate to generate Arg codons with an associated potential to impart antinuclear activity to the respective antibody (1, 3). This raises a paradox because TCN Ser codons do not have this propensity and yet are far less abundant in Ab V region genes and specifically in CDRs. Wagner and colleagues originally hypothesized that this bias toward AGY Ser codons in CDRs was due to a selection pressure to constrain AID motifs to Ag-binding regions of the B cell receptor (17). While this is plausible, our data reveal that this explanation alone cannot account for CDR AGY codon abundance because CDR AGY triplets occur predominantly in the Ser reading frame, even though AID is blind to the translational reading frame. Because TCA and TCG can mutate to stop codons by single-base changes, it is plausible that high CDR AGY/TCN ratios are due in part to selection against these codons. This may hold for TCG which had a low observed/expected ratio, but apparently not for TCA, which had an observed/expected ratio of greater than one, even though it can mutate to a stop codon by two different single-base changes. Overall the observed/expected ratios for TCN codons were greater than one in CDRs. Finally, if there was selection pressure against TCN due to the stop codon potential, we would expect that TCN would be underrepresented in CDRs relative to FRs because there is a bias for increased mutation in CDRs that cannot be explained solely by triplet sequences (13). However no such bias was seen for the Vκ genes of either species (Figure 1A)."}

{"project":"MyTest","denotations":[{"id":"27920779-20805563-34707978","span":{"begin":179,"end":180},"obj":"20805563"},{"id":"27920779-8011289-34707979","span":{"begin":182,"end":183},"obj":"8011289"},{"id":"27920779-7651532-34707980","span":{"begin":529,"end":531},"obj":"7651532"},{"id":"27920779-11859119-34707981","span":{"begin":1526,"end":1528},"obj":"11859119"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"AGY Ser codons are potentially dangerous because they easily mutate to generate Arg codons with an associated potential to impart antinuclear activity to the respective antibody (1, 3). This raises a paradox because TCN Ser codons do not have this propensity and yet are far less abundant in Ab V region genes and specifically in CDRs. Wagner and colleagues originally hypothesized that this bias toward AGY Ser codons in CDRs was due to a selection pressure to constrain AID motifs to Ag-binding regions of the B cell receptor (17). While this is plausible, our data reveal that this explanation alone cannot account for CDR AGY codon abundance because CDR AGY triplets occur predominantly in the Ser reading frame, even though AID is blind to the translational reading frame. Because TCA and TCG can mutate to stop codons by single-base changes, it is plausible that high CDR AGY/TCN ratios are due in part to selection against these codons. This may hold for TCG which had a low observed/expected ratio, but apparently not for TCA, which had an observed/expected ratio of greater than one, even though it can mutate to a stop codon by two different single-base changes. Overall the observed/expected ratios for TCN codons were greater than one in CDRs. Finally, if there was selection pressure against TCN due to the stop codon potential, we would expect that TCN would be underrepresented in CDRs relative to FRs because there is a bias for increased mutation in CDRs that cannot be explained solely by triplet sequences (13). However no such bias was seen for the Vκ genes of either species (Figure 1A)."}