6 research outputs found
Hidden breakpoints in genome alignments
During the course of evolution, an organism's genome can undergo changes that
affect the large-scale structure of the genome. These changes include gene
gain, loss, duplication, chromosome fusion, fission, and rearrangement. When
gene gain and loss occurs in addition to other types of rearrangement,
breakpoints of rearrangement can exist that are only detectable by comparison
of three or more genomes. An arbitrarily large number of these "hidden"
breakpoints can exist among genomes that exhibit no rearrangements in pairwise
comparisons.
We present an extension of the multichromosomal breakpoint median problem to
genomes that have undergone gene gain and loss. We then demonstrate that the
median distance among three genomes can be used to calculate a lower bound on
the number of hidden breakpoints present. We provide an implementation of this
calculation including the median distance, along with some practical
improvements on the time complexity of the underlying algorithm.
We apply our approach to measure the abundance of hidden breakpoints in
simulated data sets under a wide range of evolutionary scenarios. We
demonstrate that in simulations the hidden breakpoint counts depend strongly on
relative rates of inversion and gene gain/loss. Finally we apply current
multiple genome aligners to the simulated genomes, and show that all aligners
introduce a high degree of error in hidden breakpoint counts, and that this
error grows with evolutionary distance in the simulation. Our results suggest
that hidden breakpoint error may be pervasive in genome alignments.Comment: 13 pages, 4 figure
Genome sequence of Theileria parva, a bovine pathogen that transforms lymphocytes
We report the genome sequence of Theileria parva, an apicomplexan pathogen causing economic losses to smallholder farmers in Africa. The parasite chromosomes exhibit limited conservation of gene synteny with Plasmodium falciparum, and its plastid-like genome represents the first example where all apicoplast genes are encoded on one DNA strand. We tentatively identify proteins that facilitate parasite segregation during host cell cytokinesis and contribute to persistent infection of transformed host cells. Several biosynthetic pathways are incomplete or absent, suggesting substantial metabolic dependence on the host cell. One protein family that may generate parasite antigenic diversity is not telomere-associated
Draft Genome of the Filarial Nematode Parasite Brugia malayi
Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design
Large-scale multiple sequence alignment and phylogeny estimation
With the advent of next generation sequencing technologies, alignment and phylogeny estimation of datasets with thousands of sequences is being attempted. To address these challenges, new algorithmic approaches have been developed that have been able to provide substantial improvements over standard methods. This paper focuses on new approaches for ultra-large tree estimation, including methods for co-estimation of alignments and trees, estimating trees without needing a full sequence alignment, and phylogenetic placement. While the main focus is on methods with empirical performance advantages, we also discuss the theoretical guarantees of methods under Markov models of evolution. Finally, we include a discussion of the future of large-scale phylogenetic analysis