Biology subjects

Battistuzzi, F. U.

Publications and source records attributed to Battistuzzi, F. U..

5 recordsLinked to original sources

bioRxiv2021

PACAS: pairwise comparisons of aligned subsequences

Evaluation of conservation levels of alignments is a pivotal step for evolutionary analyses. Commonly used software to analyze alignments produce either site-by-site or overall measures of conservation without the ability of performing comparative analyses among sub-regions of the alignment. We have developed a stand-alone alignment analyzer (Pairwise Comparisons of Aligned Subsequences) that uses user-defined sub-regions to report various measures of conservation among pairs of sequences and between the sub-regions and the rest of the alignment. We then used this method to analyze the repetitive regions (low complexity regions; LCRs) of two genes in Plasmodium: AMA1 and CSP. We found that LCRs are not always associated with high entropy (low conservation) suggesting that some LCRs may be less likely to mutate than others. Availability and ImplementationPACAS is publicly available at https://github.com/BlabOaklandU/PACAS ContactFabia U. Battistuzzi battistu@oakland.edu Supplementary informationn/a

bioinformatics↗

bioRxiv2021

Genomic evolution of epitopes and low complexity regions in Plasmodium

Despite decades-long efforts to eradicate malaria, pathogens genomic complexity and variability continue to pose major challenges for the vaccine and drug development. Here we examined the evolutionary history of epitopes and epitope-like regions to determine whether they share underlying evolutionary mechanisms and potential functions that are relevant to pathogens interactions with the host immune response. Our comparative sequence analyses contrasted patterns of sequence conservation, amino acid composition, and protein structure of epitopes and low complexity regions (LCRs) in 21 Plasmodium species. Our results revealed many similarities in amino acid composition and preferred secondary structures between epitopes and LCRs; however, we also identified differences in evolutionary trends where LCRs exhibit overall lower sequence conservation and higher disorder. We also found that both epitopes and LCRs have a wide array of configurations, with various levels of sequence conservation and structural order. We propose that such combination of different levels of conservation and structural order between epitopes and LCRs in the same gene play a role in maintaining the functional integrity required by the pathogen along with the variability necessary to evade the host immune response, with LCRs playing a role in the evasion particularly in the vicinity of conserved epitopes. Overall, our results suggest that there are at least two categories of LCRs, where some LCRs play a potential protective role for conserved (ordered) epitopes because of their variable (or disordered) sequence, while others are less disordered and are as conserved as epitopes. The former ones may be an evolutionary necessity for Plasmodium to maintain the diversity of epitopes, while the latter category may serve currently unknown function(s) and deserve to be examined in greater detail. Our findings show that there may be many more candidate targets for future anti-malarial treatments than initially thought and that some of these targets may work across strains and species.

evolutionary biology↗

bioRxiv2020

Genome Diversity in Ukraine

The main goal of this collaborative effort is to provide genome wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for the public data release. DNBSEQ-G50 sequences, and genotypes by an Illumina GWAS chip were cross-validated on multiple samples, and additionally referenced to one sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. The genome data has been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, CNVs, SNPs and microsatellites. This study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for historic and medical research in a large understudied population. While most of the common variation is shared with other European populations, this survey of population variation contributes a number of novel SNPs and structural variants that have not been reported in the gnomAD/1KG databases representing global distribution of genomic variation. These endemic variants will become a valuable resource for designing future population and clinical studies, help address questions about ancestry and admixture, and will fill a missing place in the puzzle characterizing human population diversity in Eastern Europe. Our results indicate that genetic diversity of the Ukrainian population is uniquely shaped by the evolutionary and demographic forces, and cannot be ignored in the future genetic and biomedical studies. This data will contribute a wealth of new information bringing forth different risk and/or protective alleles. The newly discovered low frequency and local variants can be added to the current genotyping arrays for genome wide association studies, clinical trials, and in genome assessment of proliferating cancer cells.

genomics↗

bioRxiv2018

Using taxon resampling to identify species with contrasting phylogenetic signals: an empirical example in Terrabacteria

MotivationThe promise of higher phylogenetic stability through increasing dataset size within Tree of Life (TOL) reconstructions has not been fulfilled, especially for deep nodes. Among the many causes proposed are changes in species composition (taxon sampling) that could influence phylogenetic accuracy of the methods by altering the relative weight of the evolutionary histories of each individual species. This effect would be stronger in clades that are represented by few lineages, which is common in many Prokaryote phyla. Indeed, phyla with fewer taxa showed the most discordance among recent TOL studies. Thus, we implemented an approach to systematically test how the number of taxa and the identity of those taxa among a larger dataset affected the accuracy of phylogenetic reconstruction.\n\nResultsWe utilized an empirical dataset of 766 fully-sequenced proteomes for phyla within Terrabacteria as a reference for subsampled datasets that differed in both number of species and composition of species. After evaluating the backbone of trees produced as well as the internal nodes, we found that trees with fewer species were more dissimilar to the tree produced from the full dataset. Further, we found that even within scenarios consisting of the same number of taxa, the species used strongly affected phylogenetic stability. These results hold even when the tree is composed by many phyla and only one of them is being altered. Thus, the effect of taxon sampling in one group does not seem to be buffered by the presence of many other clades, making this issue relevant even to very large datasets. Our results suggest that a systematic evaluation of phylogenetic stability through taxon resampling is advisable even for very large datasets.\n\nContactbattistu@oakland.edu\n\nSupplementary informationSupplementary text and figures are available on the journals website.

bioinformatics↗

bioRxiv2017

RelTime relaxes the strict molecular clock throughout the phylogeny

The RelTime method estimates divergence times when evolutionary rates vary among lineages. Theoretical analyses show that RelTime relaxes the strict molecular clock throughout a molecular phylogeny, and it performs well in the analysis of empirical and computer simulated datasets in which evolutionary rates are variable. Lozano-Fernandez et al. (2017) found that the application of RelTime to one metazoan dataset (Erwin et al. 2011) produced equal rates for several ancient lineages, which led them to speculate that RelTime imposes a strict molecular clock for deep animal divergences. RelTime does not impose a strict molecular clock. The pattern observed by Lozano-Fernandez et al. (2017) was a result of the use of an option to assign the same rate to lineages in RelTime when the rates are not statistically significantly different. The median rate difference was 5% for many deep metazoan lineages for Erwin et al. (2011) dataset, so the rate equality was not rejected. In fact, RelTime analysis with and without the option to test rate differences produced very similar time estimates. We found that the Bayesian time estimates vary widely depending on the root priors assigned, and that the use of less restrictive priors produce Bayesian divergence times that are concordant with those from RelTime for Erwin et al. (2011) dataset. Therefore, it is prudent to discuss Bayesian estimates obtained under a range of priors in any discourse about molecular dating, including method comparisons.

evolutionary biology↗