Tracing the origin of fish immunoglobulins.

We have studied the origin of immunoglobulin genes in fish. There are two evolutionary lines of bony fish, Actinopterygii and Sarcopterygii. The former gave rise to most of the current fish and the latter to the animals that went to land. Non-teleost actinopterygians are significant evolutionary, sharing a common ancestor with sarcopterygians. There are three different immunoglob- ulin isotypes in ray-finned fish: IgM, IgD and IgT. We deduce that translocon formation in im- munoglobulins genes occurred already in non-teleost Actinopterygii. We establish a relationship between no teleosts and teleostean fish at the domain level of different immunoglobulins. We found two evolutionary lines of immunoglobulin. A line that starts from Immunoglobulin M and another from an ancestral Immunoglobulin W. The M line is stable, and the W line gives rise to the IgD of the fish. Immunoglobulin T emerges by recombination between both lines.

Immunoglobulins genes in Neoceratodus forsteri and Protopterus annectens explain the origin of the immunoglobulins of the animals that passed ashore.

Sarcopterygian fishes are a taxon of bony fishes. They include lungfish and coelacanths (six species of lungfish and two species of coelacanths). Evolutionary adaptations arose with these fish, such as the appearance of lungs and paired lobed fins that help them move over the bottom of the sea. In the Devonian period, they came ashore, and tetrapods (amphibians, reptiles, and mammals) arose from them. Within immunology, they can teach us about the emergence of immunoglobulins D, A/X, and Y already present in amphibians. We have studied the genes of the immunoglobulins in the fish Sarcopterygii Neoceratodus forsteri and Protopterus annectens. In the first fish, we find that several loci for the constant chains of immunoglobulins are distributed across 4 chromosomes. We have found four genes for IgM, a gene for IgW and a gene for IgN. In the second, we find one locus with genes for IgN and IgM and another with one gene for IgW. With these sequences, together with those obtained in other publications, we have been able to study the possible evolution and emergence of immunoglobulin classes. We conclude that there are two evolutionary lineages, one focused on IgM and very conservative, and the other focused on IgW, which allows high variability. In the case of the animals that went to land, their IgD is formed only by domains whose origin is in the W lineage. IgA/X and IgY are unique since they arose from the recombination between the two evolutionary lineagess (M and W). In both IgA/X and IgY, the CH1 and CH2 domains come from domains whose origin is the W lineage, while their CH3 and CH4 derive from the M lineage.

Gouania willdenowi is a teleost fish without immunoglobulin genes.

Immunoglobulin (Ig) genes encode antibodies in jawed vertebrates. They are essential elements of the adaptive immune response. Ig exists in soluble form or as part of the B cell membrane antigen receptor (BCR). Studies of Ig genes in fish genomes reveal the absence of Ig genes in Gouania willdenowi by deletion of the entire Ig locus from the canonical chromosomal region. The genes coding for integral BCR proteins, CD79a and CD79b, are also absent. Genes exist for T α/ß lymphocyte receptors but not for the T γ/δ receptors. The results of the genomic analysis are independently corroborated with RNA-Seq transcriptomes from other Gobiesocidae species. From the transcriptome studies, Ig is also absent from these other Gobiesocidae species, Acyrtus sp. and Tomicodon sp. Present evidence suggests that Ig is missing from all species of the Gobiesocidae family.

Insights into the evolution of IG genes in Amphibians and reptiles.

Immunoglobulins are essential proteins of the immune system to neutralize pathogens. Gene encoding B cell receptors and antibodies (Ig genes) first appeared with the emergence of early vertebrates having a jaw, and are now present in all extant jawed vertebrates, or Gnathostomata. The genes have undergone evolutionary changes. In particular, genomic structural changes corresponding to genes of the adaptive immune system were coincident or in parallel with the adaptation of vertebrates from the sea to land. In cartilaginous fish exist IgM, IgD/W, and IgNAR and in bony fish IgM, IgT, IgD. Amphibians and reptiles witnessed significant modifications both in the structure and orientation of IG genes. In particular, for these amphibians and Amniota that adapted to land, IgM and IgD genes were retained, but other isotypes arose, including genes for IgA(X)1, IgA(X)2, and IgY. Recent progress in high throughput genome sequencing is helping to uncover the IG gene structure of all jawed vertebrates. In this work, we review the work and present knowledge of immunoglobulin genes in genomes of amphibians and reptiles.

Immunoglobulin T genes in Actinopterygii.

In teleost fishes, there are three immunoglobulin isotypes named immunoglobulin M (IgM), D (IgD), and T (IgT). IgT was the last to be described in teleost fishes, and it is specific to them. From recent fish genomes, we identified and studied the immunoglobulin heavy chain genes in Actinopterygii. For this analysis, a custom bioinformatics and machine learning pipeline, we call CHfinder, was developed that identifies the exons coding for the CH domains of fish immunoglobulins. Some IgT in teleost and holostean fish found from this systematic study have not been previously described. Phylogenetic analysis of the deduced amino acid sequences of the IgT CH1 exons reveals they are similar to the CH1 of IgM. This analysis also shows that the other three domains (CH2, CH3, and CH4) were not the result of recent IgM duplication processes in Actinopterygii, demonstrating that it is an immunoglobulin of earlier origin. The bioinformatics program, CHfinder, is publicly available at https://github.com/compimmuno/CHfinder.

Snakes antibodies.

Immunoglobulins are basic molecules of the immune system of vertebrates. In previous studies we described the immunoglobulins found in two squamata reptiles, Anolis carolinensis and Eublepharis macularius. Snakes are squamata reptiles too but they have undergone an extreme evolutionary process. We therefore wanted to know how these changes affected their immunoglobulin coding genes. To perform this analysis we studied five snake transcriptomes and two genome draft sequences. Sequences coding for immunoglobulin M (IgM), immunoglobulin D (IgD) and two classes of immunoglobulin Y (IgY - named IgYa and IgYb-) were found in all of them. Moreover, the Thamnophis elegans transcriptome and Python molurus genome draft sequences showed a third class of IgY, the IgYc, whose constant region only presents three domains and lacks the CH2. All data suggest that the IgYb is the evolutionary origin of this IgYc. An exhaustive search of the light chains were carried out, being lambda the only light chain found in snakes. The results provide a clear picture of the immunoglobulins present in the suborder Serpentes.