ena-STUDY-KAROLINSKA INSITUTET-08-06-2021-12:06:58:472-751
Genomic evidence of parasexual reproduction in parasite Leishmania tropica
Single-celled kinetoplastid Leishmania tropica infects humans causing a wide range of cutaneous and often life-threatening disease pathologies. Its digenic life cycle includes meiosis in the vector sandfly and mitotic cell division in the mammalian host. The predominance of mitotic over meiotic cycles coupled with low coinfection rates of genetically distinct parasites in the sandfly can result in patchy recombination patterns. Moreover, chromosome instability during cell divisions yields aneuploidy with some chromosome copy numbers of 3 or more. Direct evidence of classical haploid meiotic gametes have not been observed in L. tropica, resulting in questions about potential parasexual mechanisms. During parasexual mating, the fusion of diploid cells creates a tetraploid intermediate that undergoes chromosomal recombination and gradual chromosomal loss. Here, genome-wide SNP diversity from 22 L. tropica isolates showed extensive aneuploidy and chromosome-specific runs of homozygosity and heterozygosity. All isolates originated in the Middle East, including one patient possessing two genetically distinct leishmaniasis infections three years apart. We found ancestries similar to the reference genome with virtually no derived alleles, then clusters of heterozygous SNPs, and then homozygous SNPs for the derived alleles on the same chromosome (36) with specific recombination breakpoints at the inferred origin of replication. Other chromosomes had similar changes at strand-switch regions separating polycistronic transcriptional units and marked changes in heterozygosity. One isolate had evidence of a chromosome 10 with a monosomic 5' end and tetrasomic 3' end with a breakpoint at a strand-switch region. This illustrates the need for genomic surveillance of tropical parasites to detect emerging hybrids that could spread more widely.
Single-celled kinetoplastid Leishmania tropica infects humans causing a wide range of cutaneous and often life-threatening disease pathologies. Its digenic life cycle includes meiosis in the vector sandfly and mitotic cell division in the mammalian host. The predominance of mitotic over meiotic cycles coupled with low coinfection rates of genetically distinct parasites in the sandfly can result in patchy recombination patterns. Moreover, chromosome instability during cell divisions yields aneuploidy with some chromosome copy numbers of 3 or more. Direct evidence of classical haploid meiotic gametes have not been observed in L. tropica, resulting in questions about potential parasexual mechanisms. During parasexual mating, the fusion of diploid cells creates a tetraploid intermediate that undergoes chromosomal recombination and gradual chromosomal loss. Here, genome-wide SNP diversity from 22 L. tropica isolates showed extensive aneuploidy and chromosome-specific runs of homozygosity and heterozygosity. All isolates originated in the Middle East, including one patient possessing two genetically distinct leishmaniasis infections three years apart. We found ancestries similar to the reference genome with virtually no derived alleles, then clusters of heterozygous SNPs, and then homozygous SNPs for the derived alleles on the same chromosome (36) with specific recombination breakpoints at the inferred origin of replication. Other chromosomes had similar changes at strand-switch regions separating polycistronic transcriptional units and marked changes in heterozygosity. One isolate had evidence of a chromosome 10 with a monosomic 5' end and tetrasomic 3' end with a breakpoint at a strand-switch region. This illustrates the need for genomic surveillance of tropical parasites to detect emerging hybrids that could spread more widely.