Kevinmcgee Week 11

trypanosomatid Ecotins chymotrypsin amastins Sphingolipids PG-galactosyltransferases pseudogenes ribonuclease glycoinositol-phospholipids prenylation

Leishmania Background

1. Leishmania Major is a tropical parasite
2. Sepctrum of disease, “Leishmaniases”
   • broad term describing a flesh eating virus specific to Leishmania
   • 2 million infections in 88 countries annually
3. Have adapted to avoid host destruction
   • curing is very hard and doesn’t always work

Genome Structure and Content

1. 32,816,678 base pairs obtained
2. 36 chromosomes
   • single continuous sequence generated for each chromosome
3. 911 RNA genes
   • Organized differently in Tritryp genomes from L. Major
4. 8272 protein coding genes
5. 663 related families
   • Smaller gene families arose from gene duplication
   • Larger families have single genes at multiple locations on the gene

Genome Comparison

1. Leishmania is compared with other organisms
   • Trypanosoma Brucei
   • Trypanosoma Cruzi
   • Leishmania has many orthologs under in these genomes
2. 910 genes not orthologs
   • “Leishmania Restricted genes”
     • responsible for key metabolic differences
3. LmjF33.1740 and LmjF33.1750
   • Macrophage migration inhibition factor
     • Similar to that in humans that deals with immunity from macrophage

Significant Genetic Findings

1. Transcription
   • L. major genome is organized into 133 clusters of tens to hundreds of protein-coding genes on same DNA strand
   • Pollycistronic transcription initiates in both directions:
     • In divergent strand-switch regions
     • terminates within the convergent strand-switch regions
   • RNAP I, II and III were found in Trytrip
     • Very different from other eukaryotes
   • Not many other homologs of RNAP were found
   • These findings, along with the polycistronic gene organization, are consistent with posttranscriptional control mechanisms being the primary determinants of Tritryp gene expression
2. RNA Processing
   • Polyadenylation is determined by trans-splicing of downstream mRNA