PMC:5118421 / 26584-28193 JSONTXT

{"project":"TEST0","denotations":[{"id":"27920779-62-68-3100250","span":{"begin":656,"end":658},"obj":"[\"11859119\"]"},{"id":"27920779-66-72-3100251","span":{"begin":660,"end":662},"obj":"[\"12943801\"]"},{"id":"27920779-70-76-3100252","span":{"begin":664,"end":666},"obj":"[\"8786330\"]"},{"id":"27920779-237-243-3100253","span":{"begin":1198,"end":1200},"obj":"[\"7916950\"]"}],"text":"For somatically generated contact residues, mutations at AGY Ser codons were the most abundant by far, and occurred ~2–3 times more often than mutations at AAY Asn codons (Figure 4B), the second most consistently mutated codon group. Most importantly, AGY Ser codons mutated to contact residues more often than any other codon group (Figure 4B), and a large proportion of these (~70%) were those defined as key Ag-contact residues. AGY mutations to codons for Arg, Asn, and Thr were the most consistent, and this was true for both contact and non-contact residues (Table 3 and data not shown). AAY triplets are also intrinsically preferred targets of SHM (13, 15, 16). However, when considering the potential to mutate to 1 of the 6 non-synonymous key contact residues (Arg, Asn, Asp, Gly, Ser, Thr, and Tyr), AGY Ser codons are able to do so via 12 out of 18 possible single-base changes. For AAY (Asn), this occurs with 8 out of 18 base changes, and for TCN, it occurs with only 6 out of 36 base substitutions (Figure 5), a result that is in agreement with the observation by Chang and Casali that CDR, but not FR sequences, are prone to acquire replacement mutations upon random point mutation (41). Collectively, the results of these analyses indicate that AGY codons contribute to Ab affinity both directly, by encoding a Ser residue, and indirectly due to the ease with which they mutate to encode other residues beneficial to the process of Ab affinity maturation. We believe this is the most straightforward explanation for the conservation of AGY codon abundance in CDRs of germline IgV-region genes."}

{"project":"2_test","denotations":[{"id":"27920779-11859119-34707973","span":{"begin":656,"end":658},"obj":"11859119"},{"id":"27920779-12943801-34707974","span":{"begin":660,"end":662},"obj":"12943801"},{"id":"27920779-8786330-34707975","span":{"begin":664,"end":666},"obj":"8786330"},{"id":"27920779-7916950-34707976","span":{"begin":1198,"end":1200},"obj":"7916950"}],"text":"For somatically generated contact residues, mutations at AGY Ser codons were the most abundant by far, and occurred ~2–3 times more often than mutations at AAY Asn codons (Figure 4B), the second most consistently mutated codon group. Most importantly, AGY Ser codons mutated to contact residues more often than any other codon group (Figure 4B), and a large proportion of these (~70%) were those defined as key Ag-contact residues. AGY mutations to codons for Arg, Asn, and Thr were the most consistent, and this was true for both contact and non-contact residues (Table 3 and data not shown). AAY triplets are also intrinsically preferred targets of SHM (13, 15, 16). However, when considering the potential to mutate to 1 of the 6 non-synonymous key contact residues (Arg, Asn, Asp, Gly, Ser, Thr, and Tyr), AGY Ser codons are able to do so via 12 out of 18 possible single-base changes. For AAY (Asn), this occurs with 8 out of 18 base changes, and for TCN, it occurs with only 6 out of 36 base substitutions (Figure 5), a result that is in agreement with the observation by Chang and Casali that CDR, but not FR sequences, are prone to acquire replacement mutations upon random point mutation (41). Collectively, the results of these analyses indicate that AGY codons contribute to Ab affinity both directly, by encoding a Ser residue, and indirectly due to the ease with which they mutate to encode other residues beneficial to the process of Ab affinity maturation. We believe this is the most straightforward explanation for the conservation of AGY codon abundance in CDRs of germline IgV-region genes."}

{"project":"MyTest","denotations":[{"id":"27920779-11859119-34707973","span":{"begin":656,"end":658},"obj":"11859119"},{"id":"27920779-12943801-34707974","span":{"begin":660,"end":662},"obj":"12943801"},{"id":"27920779-8786330-34707975","span":{"begin":664,"end":666},"obj":"8786330"},{"id":"27920779-7916950-34707976","span":{"begin":1198,"end":1200},"obj":"7916950"}],"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":"For somatically generated contact residues, mutations at AGY Ser codons were the most abundant by far, and occurred ~2–3 times more often than mutations at AAY Asn codons (Figure 4B), the second most consistently mutated codon group. Most importantly, AGY Ser codons mutated to contact residues more often than any other codon group (Figure 4B), and a large proportion of these (~70%) were those defined as key Ag-contact residues. AGY mutations to codons for Arg, Asn, and Thr were the most consistent, and this was true for both contact and non-contact residues (Table 3 and data not shown). AAY triplets are also intrinsically preferred targets of SHM (13, 15, 16). However, when considering the potential to mutate to 1 of the 6 non-synonymous key contact residues (Arg, Asn, Asp, Gly, Ser, Thr, and Tyr), AGY Ser codons are able to do so via 12 out of 18 possible single-base changes. For AAY (Asn), this occurs with 8 out of 18 base changes, and for TCN, it occurs with only 6 out of 36 base substitutions (Figure 5), a result that is in agreement with the observation by Chang and Casali that CDR, but not FR sequences, are prone to acquire replacement mutations upon random point mutation (41). Collectively, the results of these analyses indicate that AGY codons contribute to Ab affinity both directly, by encoding a Ser residue, and indirectly due to the ease with which they mutate to encode other residues beneficial to the process of Ab affinity maturation. We believe this is the most straightforward explanation for the conservation of AGY codon abundance in CDRs of germline IgV-region genes."}