Huene, Aidan Lorraine
(2022)
Molecular basis of allorecognition in the colonial cnidarian Hydractinia symbiolongicarpus.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Allorecognition is the ability to distinguish between self tissues and those of conspecifics. Among cnidarians, the molecular basis of allorecognition is best understood in the colonial hydroid, Hydractinia. Previous work has established that allorecognition is controlled by at least two linked genes, Alr1 and Alr2, which are located in a genomic region called the Allorecognition Complex (ARC). Both genes encode transmembrane proteins that have two or three extracellular domains. Both Alr1 and Alr2 are highly polymorphic and homophilically bind in trans in an isoform-specific manner. This had led to the hypothesis that trans interactions between matching Alr1 and Alr2 isoforms are involved in determining recognition specificity in Hydractinia. The evolutionary history of Alr1 and Alr2 is unclear and no homologs have been identified to date. In addition, how new alleles evolve which bear unique binding specificities is unclear due to a lack of closely related isoforms to test. Recently, advancements in sequencing have made it feasible to sequence the Hydractinia genome. I assembled and annotated three ARC haplotypes that were generated from genomic sequence obtained from a homozygous inbred Hydractinia (ARC-F) and a heterozygous wildtype Hydractinia (ARC-wt). Here, I report the identification of 41 Alr¬-like loci in ARC-F and 56 Alr¬-like loci in ARC-wt which all share a similar domain architecture. I show that Alr sequences encode domains that are novel members of the Immunoglobulin Superfamily predicted to have V-set, I-set, or Fibronectin III-like topologies. The Alr loci encode significantly different sequences and in most cases do not align. Comparing multiple alleles of the same Alr revealed that most Alr alleles appear to be very similar, though not identical. In addition to Alr1 and Alr2, a third highly polymorphic gene, Alr6, was identified. I also report my work showing that the homophilic binding specificity in Alr2 can evolve rapidly. I showcase this through allelic isoforms with six single amino acid changes that have three distinct binding specificities. These results show that allorecognition in Hydractinia is a highly specific, complex mechanism and remains one of the best described recognition systems observed in invertebrates.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
9 January 2022 |
| Date Type: |
Publication |
| Defense Date: |
3 December 2021 |
| Approval Date: |
9 January 2022 |
| Submission Date: |
9 December 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
276 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Integrative Systems Biology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
immune, immunology, recognition, structure, genome, variation, evolution, cell adhesion |
| Date Deposited: |
09 Jan 2022 22:42 |
| Last Modified: |
19 May 2023 13:57 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/42133 |
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