Trypanosomes Flashcards
Normally hap or diploid?
Diploid
How many haploid chromosomes do the tri trips have
Brucei- 11
Cruzi- 41
Major- 36
What is the closest free living relative of trips
Bodo saltans- has a larger genome
Describe Polycistronic transcription units
Genes are arranged in clusters on a single strand and lack individual promoters
How is mRNA produced in tryps
Trans splicing and polyadenylation of Polycistronic
Where does rna pol 2 start and finish in tryps
Start Strand switch regions between two divergent ptus
End ssr between convergent ptus
Similarities between trans and cis splicing
1) largely share the same mechanism- two consecutive catalytic trans esterification reactions
2) major components of the spliceosomes are conserved apart from poly a polymerase
Differences in trans and cis splicing
CIs takes out intron trans dissects pcu
Describe the general features of trypanosomes
5
1) unicellular parasites
2) both intra and extra cellular
3) complex life-cycles and multiple hosts
4) diverse disease syndromes and a global distribution
5) ancient and bio diverse
Describe Polycistronic transcription units
3
- conserved through chromosomal rearrangements
- ancestral feature before parasitism
- sub telomeres regions are species specific and so likely represent adaptions for parasitism
What is a ubiquitous feature of leishmania
Aneuploidy probably caused by chromosome replication errors
Describe genomic variation in leishmania
3
- in asexual lineage in rapid response to environmental changes
- such as drug resistance- amplification of chromosome 31
What do telomeres structures contain
Vsg and species specific genes
Describe comparative genomics
Purpose
Limitations
Revealed
Purpose- define what is unique to identify the genetic causes of species specific phenotypes
Limitations- scope- analyses content not function
-scale- small changes missed
Revealed wide spread conservation of genome content and structure through tryp genomes
Most species specific genes are cell surface glycoproteins that probably have an immune selection pressure
Describe amastin
3
Amastin is expressed by all trips although mainly in the intra cellular amastigote stage of leishmania.
Expressed on cell surface transmembrane glycoprotein
Since leishmania has parasitised vertebrates amastin has had a massive elaboration compared to its monoxenic cousins crithidia and leptomonas
What genome structure do tryps have?
Polycistronic transcription units are highly conserved
How are trypanosome and leishmania different and similar
Similar in content and organisation
Differ in features of the host-parasite interface e.g. Amastin
These compounds are the most dynamic parts of the genome
When does most regulation occur in trips %
Transcriptomic-2-35%
Proteomic 40-50%
What could comparative analysis show in terms of developmental variation in trips? + e.g.
- metabolic differences, species specific surface genes
- t. Vivax doesn’t enter midgut of the fly, they don’t express pyruvate metabolism in vertebrate stage
What has genome sequencing allowed
Determine the genetic causes of drug resistance and therefore the mechanism
Describe the sequence of reverse vaccinology
Parasite genome Screen for likely antigens Express recombinant protein Demonstrate immunogenicity to serum Demonstrate protective effect in vivo Clinical trials
What do antigens need to be to work?
5
Surface expressed Infective/visible stage Antibody epitope a Structural consistency Non-host
Describe VSG diagnosis
Variant antigen profiling of T. congolense, VAP exploits sub divisions within the tryp repertoire to provide a metric of genomic variation between individuals