Pavel Dobrynin

Genome-wide Evidence Reveals that African and Eurasian Golden Jackals Are Distinct Species

The golden jackal of Africa (Canis aureus) has long been considered a conspecific of jackals distributed throughout Eurasia, with the nearest source populations in the Middle East. However, two recent reports found that mitochondrial haplotypes of some African golden jackals aligned more closely to gray wolves (Canis lupus), which is surprising given the absence of gray wolves in Africa and the phenotypic divergence between the two species. Moreover, these results imply the existence of a previously unrecognized phylogenetically distinct species despite a long history of taxonomic work on African canids. To test the distinct-species hypothesis and understand the evolutionary history that would account for this puzzling result, we analyzed extensive genomic data including mitochondrial genome sequences, sequences from 20 autosomal loci (17 introns and 3 exon segments), microsatellite loci, X- and Y-linked zinc-finger protein gene (ZFX and ZFY) sequences, and whole-genome nuclear sequences in African and Eurasian golden jackals and gray wolves. Our results provide consistent and robust evidence that populations of golden jackals from Africa and Eurasia represent distinct monophyletic lineages separated for more than one million years, sufficient to merit formal recognition as different species: C. anthus (African golden wolf) and C. aureus (Eurasian golden jackal). Using morphologic data, we demonstrate a striking morphologic similarity between East African and Eurasian golden jackals, suggesting parallelism, which may have misled taxonomists and likely reflects uniquely intense interspecific competition in the East African carnivore guild. Our study shows how ecology can confound taxonomy if interspecific competition constrains size diversification.

Genomic Legacy of the African Cheetah, Acinonyx jubatus

BackgroundPatterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations.ResultsHere the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084–12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p<0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah’s extremely high (>80 %) pleiomorphic sperm.ConclusionsThe study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species’ natural history, physiological adaptations and unique reproductive disposition.

Genome-Wide Mycobacterium tuberculosis Variation (GMTV) Database: A New Tool for Integrating Sequence Variations and Epidemiology

BackgroundTuberculosis (TB) poses a worldwide threat due to advancing multidrug-resistant strains and deadly co-infections with Human immunodeficiency virus. Today large amounts of Mycobacterium tuberculosis whole genome sequencing data are being assessed broadly and yet there exists no comprehensive online resource that connects M. tuberculosis genome variants with geographic origin, with drug resistance or with clinical outcome.DescriptionHere we describe a broadly inclusive unifying Genome-wide Mycobacterium tuberculosis Variation (GMTV) database, (http://mtb.dobzhanskycenter.org) that catalogues genome variations of M. tuberculosis strains collected across Russia. GMTV contains a broad spectrum of data derived from different sources and related to M. tuberculosis molecular biology, epidemiology, TB clinical outcome, year and place of isolation, drug resistance profiles and displays the variants across the genome using a dedicated genome browser. GMTV database, which includes 1084 genomes and over 69,000 SNP or Indel variants, can be queried about M. tuberculosis genome variation and putative associations with drug resistance, geographical origin, and clinical stages and outcomes.ConclusionsImplementation of GMTV tracks the pattern of changes of M. tuberculosis strains in different geographical areas, facilitates disease gene discoveries associated with drug resistance or different clinical sequelae, and automates comparative genomic analyses among M. tuberculosis strains.

Annotated features of domestic cat – Felis catus genome

BackgroundDomestic cats enjoy an extensive veterinary medical surveillance which has described nearly 250 genetic diseases analogous to human disorders. Feline infectious agents offer powerful natural models of deadly human diseases, which include feline immunodeficiency virus, feline sarcoma virus and feline leukemia virus. A rich veterinary literature of feline disease pathogenesis and the demonstration of a highly conserved ancestral mammal genome organization make the cat genome annotation a highly informative resource that facilitates multifaceted research endeavors.FindingsHere we report a preliminary annotation of the whole genome sequence of Cinnamon, a domestic cat living in Columbia (MO, USA), bisulfite sequencing of Boris, a male cat from St. Petersburg (Russia), and light 30× sequencing of Sylvester, a European wildcat progenitor of cat domestication. The annotation includes 21,865 protein-coding genes identified by a comparative approach, 217 loci of endogenous retrovirus-like elements, repetitive elements which comprise about 55.7% of the whole genome, 99,494 new SNVs, 8,355 new indels, 743,326 evolutionary constrained elements, and 3,182 microRNA homologues. The methylation sites study shows that 10.5% of cat genome cytosines are methylated. An assisted assembly of a European wildcat, Felis silvestris silvestris, was performed; variants between F. silvestris and F. catus genomes were derived and compared to F. catus.ConclusionsThe presented genome annotation extends beyond earlier ones by closing gaps of sequence that were unavoidable with previous low-coverage shotgun genome sequencing. The assembly and its annotation offer an important resource for connecting the rich veterinary and natural history of cats to genome discovery.

Epigenetic Patterns Modulate the Connection Between Developmental Dynamics of Parenting and Offspring Psychosocial Adjustment

This study attempted to establish and quantify the connections between parenting, offspring psychosocial adjustment, and the epigenome. The participants, 35 African American young adults (19 females and 16 males; age = 17-29.5 years), represented a subsample of a 3-wave longitudinal 15-year study on the developmental trajectories of low-income urban mother-offspring dyads. Mothers were assessed on their perceptions of maternal stress at each wave. Offspring were assessed on their perceptions of maternal parenting at each wave and on their adaptive and maladaptive behavior at the last wave. Genome-wide DNA methylation in peripheral T lymphocytes at the third wave was assayed using Methyl Binding Domain(MBD) sequencing. Statistically significant associations were identified between the change in offsprings perception of parenting from middle childhood to adulthood and the DNA methylation in offsprings adult genomes. Specifically, the slope of perceived parental rejection across the 3 time points was related to an increase in methylation, or a potential downregulation, of 565 genes thought to be involved in the control of a broad spectrum of biological functions generally related to cellular signaling. A subset of these epigenetic marks, clustered in 23 genes, some of which participate in the development and functioning of the CNS, were in turn associated with psychosocial adjustment as captured by interpersonal relationships and emotional self-evaluation. This appears to be one of the first investigations of the modulating role of the methylome in associations between developmental dynamics of parenting throughout the formative years of child and adolescent development and psychosocial adjustment in adulthood.

Cookiecutter: a tool for kmer-based read filtering and extraction

Motivation Kmer-based analysis is a powerful method used in read error correction and implemented in various genome assembly tools. A number of read processing routines include extracting or removing sequence reads from the results of high-throughput sequencing experiments prior to further analysis. Here we present a new approach to sorting or filtering of raw reads based on a provided list of kmers. Results We developed Cookiecutter — a computational tool for rapid read extraction or removing according to a provided list of k-mers generated from a FASTA file. Cookiecutter is based on the implementation of the Aho-Corasik algorithm and is useful in routine processing of high-throughput sequencing datasets. Cookiecutter can be used for both removing undesirable reads and read extraction from a user-defined region of interest. Availability The open-source implementation with user instructions can be obtained from GitHub: https://github.com/ad3002/Cookiecutter.

Molecular genetic analysis of Mycobacterium tuberculosis strains spread in different patient groups in St. Petersburg, Russia.

Molecular epidemiological features of Mycobacterium tuberculosis strains among different patient groups in Russia have not been studied well. The aim of our study was to compare the genotypes of M. tuberculosis strains circulating among tuberculosis (TB) patients from different groups: homeless, human immunodeficiency virus (HIV)-infected, prisoners, and the general population of St. Petersburg citizens. One hundred and forty-two M. tuberculosis complex isolates from different TB patient groups were studied using the spacer oligonucleotide typing (spoligotyping) method. The majority of the studied M. tuberculosis isolates in all groups belonged to the Beijing family (55% among homeless; 77% among HIV-infected; 60% among the general population; 81% among prisoners). There were no significant differences in the Beijing family prevalence among homeless patients, HIV/TB co-infected patients, and the general population of TB patients. The lowest genetic diversity of the pathogen was detected among imprisoned patients. The results of our study demonstrate that M. tuberculosis strains circulating among patients from high-risk groups are also spread among the general population of St. Petersburg citizens.

Mitogenomic sequences support a north–south subspecies subdivision within Solenodon paradoxus

Abstract Solenodons are insectivores found only in Hispaniola and Cuba, with a Mesozoic divergence date versus extant mainland mammals. Solenodons are the oldest lineage of living eutherian mammal for which a mitogenome sequence has not been reported. We determined complete mitogenome sequences for six Hispaniolan solenodons (Solenodon paradoxus) using next-generation sequencing. The solenodon mitogenomes were 16,454–16,457 bp long and carried the expected repertoire of genes. A mitogenomic phylogeny confirmed the basal position of solenodons relative to shrews and moles, with solenodon mitogenomes estimated to have diverged from those of other mammals ca. 78 Mya. Control region sequences of solenodons from the northern (n = 3) and southern (n = 5) Dominican Republic grouped separately in a network, with FST = 0.72 (p = 0.036) between north and south. This regional genetic divergence supports previous morphological and genetic reports recognizing northern (S. p. paradoxus) and southern (S. p. woodi) subspecies in need of separate conservation plans.

Genome Sequencing and Comparative Analysis of Saccharomyces cerevisiae Strains of the Peterhof Genetic Collection

The Peterhof genetic collection of Saccharomyces cerevisiae strains (PGC) is a large laboratory stock that has accumulated several thousands of strains for over than half a century. It originated independently of other common laboratory stocks from a distillery lineage (race XII). Several PGC strains have been extensively used in certain fields of yeast research but their genomes have not been thoroughly explored yet. Here we employed whole genome sequencing to characterize five selected PGC strains including one of the closest to the progenitor, 15V-P4, and several strains that have been used to study translation termination and prions in yeast (25-25-2V-P3982, 1B-D1606, 74-D694, and 6P-33G-D373). The genetic distance between the PGC progenitor and S288C is comparable to that between two geographically isolated populations. The PGC seems to be closer to two bakery strains than to S288C-related laboratory stocks or European wine strains. In genomes of the PGC strains, we found several loci which are absent from the S288C genome; 15V-P4 harbors a rare combination of the gene cluster characteristic for wine strains and the RTM1 cluster. We closely examined known and previously uncharacterized gene variants of particular strains and were able to establish the molecular basis for known phenotypes including phenylalanine auxotrophy, clumping behavior and galactose utilization. Finally, we made sequencing data and results of the analysis available for the yeast community. Our data widen the knowledge about genetic variation between Saccharomyces cerevisiae strains and can form the basis for planning future work in PGC-related strains and with PGC-derived alleles.

Chromosomer: a reference-based genome arrangement tool for producing draft chromosome sequences

BackgroundAs the number of sequenced genomes rapidly increases, chromosome assembly is becoming an even more crucial step of any genome study. Since de novo chromosome assemblies are confounded by repeat-mediated artifacts, reference-assisted assemblies that use comparative inference have become widely used, prompting the development of several reference-assisted assembly programs for prokaryotic and eukaryotic genomes.FindingsWe developed Chromosomer – a reference-based genome arrangement tool, which rapidly builds chromosomes from genome contigs or scaffolds using their alignments to a reference genome of a closely related species. Chromosomer does not require mate-pair libraries and it offers a number of auxiliary tools that implement common operations accompanying the genome assembly process.ConclusionsDespite implementing a straightforward alignment-based approach, Chromosomer is a useful tool for genomic analysis of species without chromosome maps. Putative chromosome assemblies by Chromosomer can be used in comparative genomic analysis, genomic variation assessment, potential linkage group inference and other kinds of analysis involving contig or scaffold mapping to a high-quality assembly.