Heavy Chain V Region Diversity in the Duck-Billed Platypus (<i>Ornithorhynchus anatinus</i>): Long and Highly Variable Complementarity-Determining Region 3 Compensates for Limited Germline Diversity

Johansson, Jeannette; Aveskogh, Maria; Munday, B. L.; Hellman, Lars

doi:10.4049/jimmunol.168.10.5155

Cited by 47 publications

(30 citation statements)

References 49 publications

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“…Our analyses would suggest that this D-D junction formation, along with high C content and the intrinsic flexibility of sequences biased toward G and S, can create long CDR3s that can contain intra or even inter-CDR disulfide bridges. These covalent bonds between CDRs are analogous to those observed at high frequency in the Igs of other animals such as camels (48), shark IgNARs (49,62), cows (63)(64)(65), pigs (66), and even the duckbilled platypus (67).…”

Section: Discussionsupporting

confidence: 53%

Fundamental Characteristics of the Immunoglobulin VH Repertoire of Chickens in Comparison with Those of Humans, Mice, and Camelids

Oficjalska

Lambert

et al. 2012

The Journal of Immunology

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Examination of 1269 unique naive chicken VH sequences showed that the majority of positions in the framework (FW) regions were maintained as germline, with high mutation rates observed in the CDRs. Many FW mutations could be clearly related to the modulation of CDR structure or the VH–VL interface. CDRs 1 and 2 of the VH exhibited frequent mutation in solvent-exposed positions, but conservation of common structural residues also found in human CDRs at the same positions. In comparison with humans and mice, the chicken CDR3 repertoire was skewed toward longer sequences, was dominated by small amino acids (G/S/A/C/T), and had higher cysteine (chicken, 9.4%; human, 1.6%; and mouse, 0.25%) but lower tyrosine content (chicken, 9.2%; human, 16.8%; and mouse 26.4%). A strong correlation (R2 = 0.97) was observed between increasing CDR3 length and higher cysteine content. This suggests that noncanonical disulfides are strongly favored in chickens, potentially increasing CDR stability and complexity in the topology of the combining site. The probable formation of disulfide bonds between CDR3 and CDR1, FW2, or CDR2 was also observed, as described in camelids. All features of the naive repertoire were fully replicated in the target-selected, phage-displayed repertoire. The isolation of a chicken Fab with four noncanonical cysteines in the VH that exhibits 64 nM (KD) binding affinity for its target proved these constituents to be part of the humoral response, not artifacts. This study supports the hypothesis that disulfide bond-constrained CDR3s are a structural diversification strategy in the restricted germline v-gene repertoire of chickens.

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Section: Discussionsupporting

confidence: 53%

Fundamental Characteristics of the Immunoglobulin VH Repertoire of Chickens in Comparison with Those of Humans, Mice, and Camelids

Oficjalska

Lambert

et al. 2012

The Journal of Immunology

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“…A similar pattern in V region evolution was recently observed for the heavy chain in the platypus, where all V genes were found to form a separate branch on a distance tree. However, due to large variations in both length and sequence of the CDR3 region, the heavy chain was found to be highly variable in the antigenbinding region of the antibody [25]. The results from experiments on the Vk repertoire in the platypus now adds additional support to the notion that deletions of entire V region clans or families, followed by successive rounds of gene duplications, "a birth and death process", may be a relatively common phenomenon during vertebrate evolution [26].…”

Section: Discussionmentioning

confidence: 77%

“…Information from the genomic PCR analysis confirmed this conclusion, and showed that the C regions are organized in tandem where each C region is preceded by one or possibly a few J segments. Based on the Southern blot analysis, the sequences of the different cDNA and the genomic PCR, the tentative organization is therefore as follows, (V) [15][16][17][18][19][20][21][22][23][24][25] -(J-J-J-CkI)-(JCkII)-(J-CkIII)-(J-CkIV?). This organization shows clear similarities with the organization of the k locus in several placental mammals.…”

Section: Discussionmentioning

confidence: 99%

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High variability in complementarity‐determining regions compensates for a low number of V gene families in the λ light chain locus of the platypus

Johansson¹,

Salazar²,

Aveskogh³

et al. 2005

Eur J Immunol

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Based on the analysis of a panel of variable (V) region sequences from the Australian duck-billed platypus and the Australian short beaked echidna, the monotremes were found to express a highly diversified Vk repertoire. High variability was observed both in sequence and in length of all three CDR regions. However, all monotreme sequences were found to form a separate branch on a distance tree, and the monotremes appear to express only two Vk gene families. The appearance of all Vk gene segments in one branch on the distance tree gives further support for the notion that deletions of entire V region clans or families, followed by successive rounds of gene duplications may be a relatively common phenomenon during vertebrate evolution. Four different constant region sequences were also identified and a preferential use of certain J segments to each constant region was observed. A more detailed picture of the locus was obtained by analysis of genomic DNA by Southern blot and PCR. The organization of the lambda locus involves multiple V and several constant region genes with one or several joining segments positioned upstream of each constant region, similar to the organization in mouse and man. An mRNA frequency analysis shows that the k light chain accounts for more than 90% of the light chain transcripts in the spleen. The abundance and the high variability indicate that light chain diversity at the k locus contributes significantly to the antigen-binding repertoire in monotremes. A high k to j light chain ratio also indicates that variability in the CDR regions is more important for the repertoire size than the total number of V gene families.

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“…In contrast, other species (e.g., rabbits, cattle, platypus, and chickens) have limited germline V H diversity. In these cases, the germline V H within a species typically share Ͼ80% nucleotide identity, and may be only a single V H family or a set of recently derived V H families (7,8).…”

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confidence: 99%

Unusually Similar Patterns of Antibody V Segment Diversity in Distantly Related Marsupials

Baker

Belov

Miller

2005

The Journal of Immunology

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A pattern of coevolution between the V gene segments of Ig H and L chains has been noted previously by several investigators. Species with restricted germline VH diversity tend to have limited germline VL diversity, whereas species with high levels of germline VH diversity have more diverse VL gene segments. Evidence for a limited pool of VH but diverse VL gene segments in a South American opossum, Monodelphis domestica, is consistent with this marsupial being an exception to the pattern. To determine whether M. domestica is unique or the norm for marsupials, the VH and VL of an Australian possum, Trichosurus vulpecula, were characterized. The Ig repertoire in T. vulpecula is also derived from a restricted VH pool but a diverse VL pool. The VL gene segments of T. vulpecula are highly complex and contain lineages that predate the separation of marsupials and placental mammals. Thus, neither marsupial follows a pattern of coevolution of VH and VL gene segments observed in other mammals. Rather, marsupial VH and VL complexity appears to be evolving divergently, retaining diversity in VL perhaps to compensate for limited VH diversity. There is a high degree of similarity between the VH and VL in M. domestica and T. vulpecula, with the majority of VL families being shared between both species. All marsupial VH sequences isolated so far form a common clade of closely related sequences, and in contrast to the VL genes, the VH likely underwent a major loss of diversity early in marsupial evolution.

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Heavy Chain V Region Diversity in the Duck-Billed Platypus (Ornithorhynchus anatinus): Long and Highly Variable Complementarity-Determining Region 3 Compensates for Limited Germline Diversity

Cited by 47 publications

References 49 publications

Fundamental Characteristics of the Immunoglobulin VH Repertoire of Chickens in Comparison with Those of Humans, Mice, and Camelids

Fundamental Characteristics of the Immunoglobulin VH Repertoire of Chickens in Comparison with Those of Humans, Mice, and Camelids

High variability in complementarity‐determining regions compensates for a low number of V gene families in the λ light chain locus of the platypus

Unusually Similar Patterns of Antibody V Segment Diversity in Distantly Related Marsupials

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