Biology subjects

Ponger, L.

Publications and source records attributed to Ponger, L..

6 recordsLinked to original sources

bioRxiv2026

Karyotypic evolution in a diverse primate clade and the role of chromosomal fissions as barriers to gene flow

The classical model of chromosomal speciation is based on the observation that divergent species often differ in chromosome numbers and that heterokaryotypic hybrids show reduced fitness. Furthermore, positive correlations between the rates of karyotype evolution and speciation have been established in several groups of organisms. Yet, the mechanisms that make some lineages more prone to chromosomal fissions and fusions than others, and the causal role of such karyotype changes in speciation, are poorly understood. Here, we focus on the taxonomically and karyotypically diverse group of African monkeys, the guenons (tribe Cercopithecini), consisting of ~35 species with diploid chromosome numbers ranging from 48 to 72. We generated de novo genome assemblies for eight species with different karyotypes, and incorporated publicly available genomes from additionally three guenon species. Using the rhesus macaque as an outgroup, we identified 28 independent chromosomal fissions and 4 fusions in guenons. In line with previous cytogenetic studies, repeat composition around chromosomal breakpoints suggested that most fissions were non-centromeric, requiring the evolution of a new centromere in at least one of the fission products. In contrast to the expectation under strong underdominance, we found a paraphyletic distribution of several chromosomal fissions. Some of these phylogenetically discordant events could have resulted from interspecific hybridization, whereas others are more likely caused by incomplete lineage sorting, suggesting that fissioned and non-fissioned homologs segregated in ancestral guenon lineages for millions of years. Nevertheless, we find evidence for reduced introgression on rearranged chromosomes in an ancient cross-karyotypic gene flow event between Cercopithecus cephus and C. pogonias. Although this suggests that chromosomal fissions may have constituted barriers to gene flow in the guenon evolution, the signal was inconclusive or absent in two other investigated gene flow events. This study provides important first insights into the remarkable karyotypic diversification of guenons, and its role in generating reproductive barriers.

evolutionary biology↗

bioRxiv2026

Evolutionary history of alpha satellite DNA in Cercopithecini: comparative cytogenomics highlights the diversification pattern of primate centromere repeats

BackgroundAlpha satellites, a superfamily of AT-rich tandem repeats, are the primary DNA component of centromeres in Platyrrhini and Catarrhini. Analyses of the human genome suggest that centromeres behave like biological ridges, with new alpha satellite families expanding at the centromere core, splitting and displacing older ones towards the pericentromeres. The Cercopithecini tribe, which displays an unusual chromosomal evolution involving multiple chromosomal fissions and centromere formations, represents a promising model to enhance our understanding of alpha satellite DNA evolutionary history. We previously applied targeted sequencing to centromere DNA from two distant species drawn from the Cercopithecini terrestrial and arboreal lineages, and characterized six alpha satellite families exhibiting varying mean sequence identities. MethodsCombining classical and molecular cytogenetics, we mapped the chromosomal distribution of these alpha satellite families across 13 Cercopithecini, one Papionini, and one Colobinae species. A nuclear marker-based phylogeny provided an evolutionary framework for interpretation. ResultsOur phylogeny identifies the terrestrial and arboreal lineages, and a newly designated swamp clade. We observed significant interspecies variations in alpha satellite patterns, including differences in presence/absence and distinct chromosomal distribution patterns (centromeric, pericentromeric, or subtelomeric). Families previously described as heterogeneous (83-87% mean sequence identity) exhibit a centromeric position in the swamp lineage, which is characterized by conserved karyotypes. In contrast, these families show a pericentromeric distribution in the terrestrial and arboreal lineages, replaced at the centromere core by more homogeneous families (95-98% mean sequence identity). In the arboreal clade, which is characterized by highly fissioned karyotypes, putative evolutionary new centromeres show a unique co-occurrence of highly homogeneous and heterogeneous families. Conclusion & ImplicationsWe propose a comprehensive evolutionary scenario for alpha satellite DNA in Cercopithecini, where younger families arise at the centromere core, shift toward the pericentromeres as they age, and eventually face extinction. Our study suggests that alpha satellite DNA and chromosomes evolve in an interdependent manner, with satellite diversification and displacement occurring in parallel with chromosome fissions and centromere repositioning. This comparative cytogenomic approach provides both support for the human-based evolutionary model for alpha satellite DNA and novel temporal insights into its diversification dynamics. Beyond evolutionary genomics, our findings highlight the potential of alpha satellite DNA to complement systematic studies in deciphering complex primate evolutionary histories.

evolutionary biology↗

bioRxiv2023

Comparative transcriptomics reveal a novel tardigrade specific DNA binding protein induced in response to ionizing radiation

Tardigrades, microscopic animals found in virtually all ecosystems, are renowned for their remarkable ability to withstand extreme conditions. Recent studies have identified novel tardigrade specific protein families that aid in resistance to desiccation and ionizing radiation (IR). Notably, a tardigrade specific DNA binding protein called Dsup (for DNA damage suppressor) has been found to protect from X-ray damage in human cells and from hydroxyl radicals in vitro. However, Dsup has only been found in two species within the Hypsibioidea superfamily. To better understand mechanisms underlying radio-resistance in the Tardigrada phylum, we first characterized DNA damage and repair in response to IR in the model species Hypsibius exemplaris. By analysis of phosphorylated H2AX, we demonstrated the induction and repair of DNA double-strand breaks after IR exposure. Importantly, the rate of single-strand breaks induced was roughly equivalent to that in human cells, suggesting that DNA repair plays a predominant role in the remarkable radio-resistance of tardigrades. In order to identify novel tardigrade specific genes involved, we next conducted a comparative transcriptomics across three species, H. exemplaris, Acutuncus antarcticus and Paramacrobiotus fairbanksi, the latter belonging to the Macrobiotoidea superfamily known to lack Dsup homologs. In all three species, many genes of DNA repair were among the most strongly overexpressed genes alongside a novel tardigrade specific gene, named Tardigrade DNA damage Response protein 1 (TDR1). We found that TDR1 protein interacts with DNA and forms aggregates at high concentration suggesting it may condensate DNA and act by preserving chromosome organization until DNA repair is accomplished. Remarkably, when expressed in human cells, TDR1 improved resistance to Bleomycin, a radiomimetic drug. Based on these findings, we propose that TDR1 is a novel tardigrade specific gene responsible for conferring resistance to IR. Our study sheds light on mechanisms of DNA repair helping to cope with high levels of DNA damage. Furthermore, it suggests that at least two tardigrade specific genes, respectively for Dsup and TDR1, have independently evolved DNA-binding functions that contribute to radio-resistance in the Tardigrada phylum.

molecular biology↗

bioRxiv2022

DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness

Aberrant DNA methylation is a well-known feature of tumours and has been associated with metastatic melanoma. However, since melanoma cells are highly heterogeneous, it has been challenging to use affected genes to predict tumour aggressiveness, metastatic evolution, and patients outcomes. We hypothesized that common aggressive hypermethylation signatures should emerge early in tumorigenesis and should be shared in aggressive cells, independent of the physiological context under which this trait arises. We compared paired melanoma cell lines with the following properties: (i) each pair comprises one aggressive counterpart and its parental cell line, and (ii) the aggressive cell lines were each obtained from different host and their environment (human, rat, and mouse), though starting from the same parent cell line. Next, we developed a multi-step genomic pipeline that combines the DNA methylome profile with a chromosome cluster-oriented analysis. A total of 229 differentially hypermethylated genes were commonly found in the aggressive cell lines. Genome localization analysis revealed hypermethylation peaks and clusters, identifying eight hypermethylated gene promoters for validation in tissues from melanoma patients. Five CpG identified in primary melanoma tissues were transformed into a DNA methylation score that can predict survival (Log-rank test, p=0.0008). This strategy is potentially universally applicable to other diseases involving DNA methylation alterations.

cancer biology↗

bioRxiv2021

Nucleosome positioning on large tandem DNA repeats of the '601' sequence engineered in Saccharomyces cerevisiae

The so-called 601 DNA sequence is often used to constrain the position of nucleosomes on a DNA molecule in vitro. Although the ability of the 147 base pair sequence to precisely position a nucleosome in vitro is well documented, in vivo application of this property has been explored only in a few studies and yielded contradictory conclusions. Our goal in the present study was to test the ability of the 601 sequence to dictate nucleosome positioning in Saccharomyces cerevisiae in the context of a long tandem repeat array inserted in a yeast chromosome. We engineered such arrays with three different repeat size, namely 167, 197 and 237 base pairs. Although our arrays are able to position nucleosomes in vitro as expected, analysis of nucleosome occupancy on these arrays in vivo revealed that nucleosomes are not preferentially positioned as expected on the 601-core sequence along the repeats and that the measured nucleosome repeat length does not correspond to the one expected by design. Altogether our results demonstrate that the rules defining nucleosome positions on this DNA sequence in vitro are not valid in vivo, at least in this chromosomal context, questioning the relevance of using the 601 sequence in vivo to achieve precise nucleosome positioning on designer synthetic DNA sequences.

synthetic biology↗

bioRxiv2021

Marine gregarine genomes illuminate current understanding of apicomplexan glideosome

Our current view of the evolutionary history, coding and adaptive capacities of Apicomplexa, protozoan parasites of a wide range of metazoan, is currently strongly biased toward species infecting humans, as data on early diverging apicomplexan lineages infecting invertebrates is extremely limited. Here, we characterized the genome of the marine eugregarine Porospora gigantea, intestinal parasite of Lobsters, remarkable for the macroscopic size of its vegetative feeding forms (trophozoites) and its gliding speed, the fastest so far recorded for Apicomplexa. Two highly syntenic genomes named A and B were assembled. Similar in size (~9 Mb) and coding capacity (~5300 genes), A and B genomes are 10.8% divergent at the nucleotide level, corresponding to 16-38 My in divergent time. Orthogroup analysis across 25 (proto)Apicomplexa species, including Gregarina niphandrodes, showed that A and B are highly divergent from all other known apicomplexan species, revealing an unexpected breadth of diversity. Phylogenetically these two species branch sister to Cephaloidophoroidea, and thus expand the known crustacean gregarine superfamily. The genomes were mined for genes encoding proteins necessary for gliding, a key feature of apicomplexans parasites, currently studied through the molecular model called glideosome. Sequence analysis shows that actin-related proteins and regulatory factors are strongly conserved within apicomplexans. In contrast, the predicted protein sequences of core glideosome proteins and adhesion proteins are highly variable among apicomplexan lineages, especially in gregarines. These results confirm the importance of studying gregarines to widen our biological and evolutionary view of apicomplexan species diversity, and to deepen our understanding of the molecular bases of key functions enabling parasitism, such as the glideosome.

genomics↗