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. 2021 Oct 27;15(10):e0009838.
doi: 10.1371/journal.pntd.0009838. eCollection 2021 Oct.

X-treme loss of sequence diversity linked to neo-X chromosomes in filarial nematodes

Affiliations

X-treme loss of sequence diversity linked to neo-X chromosomes in filarial nematodes

John Mattick et al. PLoS Negl Trop Dis. .

Abstract

The sequence diversity of natural and laboratory populations of Brugia pahangi and Brugia malayi was assessed with Illumina resequencing followed by mapping in order to identify single nucleotide variants and insertions/deletions. In natural and laboratory Brugia populations, there is a lack of sequence diversity on chromosome X relative to the autosomes (πX/πA = 0.2), which is lower than the expected (πX/πA = 0.75). A reduction in diversity is also observed in other filarial nematodes with neo-X chromosome fusions in the genera Onchocerca and Wuchereria, but not those without neo-X chromosome fusions in the genera Loa and Dirofilaria. In the species with neo-X chromosome fusions, chromosome X is abnormally large, containing a third of the genetic material such that a sizable portion of the genome is lacking sequence diversity. Such profound differences in genetic diversity can be consequential, having been associated with drug resistance and adaptability, with the potential to affect filarial eradication.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Pi across B. malayi and B. pahangi samples from multiple laboratory backgrounds.
Pi was calculated across each of the B. malayi and B. pahangi contigs/scaffolds using VCFTools on a combined VCF file containing all samples. The results are organized by chromosome and Nigon elements. Chromosome X shows a distinct lack of nucleotide diversity relative to the autosomes. The lack of diversity on chromosome X appears to be present in nematodes from all laboratory centers for B. malayi and in both endemic and laboratory populations for B. pahangi. The plots for chromosome X are larger reflecting the increased size of chromosome X which is approximately twice the size of the autosomes. Chromosome Y is not resolved in either organism, and as such Pi could not be calculated.
Fig 2
Fig 2. Pi across filarial nematode species and model organisms.
Pi was calculated across B. malayi, B. pahangi, W. bancrofti, O. volvulus, L. loa, D. immitis, D. melanogaster and C. elegans using VCFTools on a combined VCF file containing all samples for each of those species. For all nematode species, contigs were assigned to a Nigon element based on their homology to B. malayi, O. volvulus and C. elegans. Values of Pi were log10-transformed to more readily visualize the distributions. Filarial nematodes with neo-X chromosomes (Nigon-D/Nigon-X in Brugia spp. and W. bancrofti and NigonD/Nigon-E in O. volvulus) have a significantly depressed Pi compared to autosomal Nigon elements or X chromosomes in other species (Nigon-D in L. loa and D. immitis, Nigon-X in C. elegans, and chromosome X in D. melanogaster). This suggests that the loss of diversity observed in B. malayi and B. pahangi are not limited to those species and related to the formation of the neo-X chromosome. Chromosome 4 in D. melanogaster also has a decrease in Pi; it is a small chromosome sometimes referred to as the dot chromosome that is largely heterochromatic and may formerly have been a sex chromosome [74].
Fig 3
Fig 3. Principal component analysis of B. malayi and B. pahangi samples.
Principal component analyses of the B. malayi (A) and B. pahangi (B) samples were conducted using PLINK with default parameters on each individual sample for each population, and the resulting outputs were imported into R and plotted using geom_point from ggplots. All of the FR3-derived B. malayi samples cluster very tightly together, except for those derived from the Lucknow strain, which are separated by principal component 2. Principal component 1 primarily divides the 4 samples from Thailand, which not only are distinct from FR3-derived worms, but are much more distinct from each other than FR3-derived worms are from each other. The FR3 single adult male B. pahangi all cluster together, while samples from wild infected cats from Malaysia appear to dominate the variation along both principal components.
Fig 4
Fig 4. Phylogenetic trees of conserved nematode BUSCO genes and mitochondria between filarial species.
Conserved genes predicted by BUSCO in B. malayi, B. pahangi, W. bancrofti, B. timori and O. volvulus were separated out by their location and divided based on their presence on chromosome X of B. malayi and B. pahangi (A) or the autosomes of those species (B). These gene sets were used to construct phylogenetic trees using IQ-TREE (bootstrap = 1000) that were midpoint rooted in IQ-TREE (https://itol.embl.de/). (C) Mitochondrial genome sequences of these organisms were aligned via MAFFT, and trees were generated via IQ-TREE. The relationships between filarial species consistently show B. malayi and B. timori as more closely related to each other than to B. pahangi such that any loss of chromosome X diversity likely predates the divergence of the three organisms.
Fig 5
Fig 5. Phylogenetic relationships related to sex chromosome Nigon content.
The phylogenetic relationship of filarial nematodes is shown as adapted from Lefoulon et al. [75]. Nigon element assignments for the sex chromosomes are shown when known or inferred previously [12]. The loss of diversity on the sex chromosome co-occurs with the instances of chromosomal fusions between Nigon-IV and Nigon-X in ONC5 and between Nigon-IV and Nigon-V in ONC3, but does not appear to be present in species that do not contain the chromosomal fusion in either the ONC3 or ONC5 clades.

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