Biology subjects

Navarro-Dominguez, B.

Publications and source records attributed to Navarro-Dominguez, B..

4 recordsLinked to original sources

bioRxiv2024

Adaptive advantage of deletion repair in the N terminal domain of the SARS-CoV-2 spike protein in variants of concern

Mutations within the N-terminal domain (NTD) of the spike (S) protein are critical for the emergence of successful SARS-CoV-2 viral lineages. The NTD has been repeatedly impacted by deletions, often exhibiting complex and dynamic patterns, such as the recurrent emergence and disappearance of deletions in dominant variants. This study investigates the influence of repair of NTD lineage-defining deletions found in the BA.1 lineage (Omicron variant) on viral success. We performed comparative genomic analyses of more than 10 million SARS-CoV-2 genomes from GISAID to decipher the transmission success of viruses lacking S:{Delta}H69/V70, S:{Delta}V143/Y145, or both. These findings were contrasted against a screening of publicly available raw sequencing data, revealing substantial discrepancies between data repositories, suggesting that spurious deletion repair observations in GISAID may result from systematic artifacts. Specifically, deletion repair events were approximately an order of magnitude less frequent in the read-run survey. Our results suggest that deletion repair events are rare, isolated events with limited direct influence on SARS-CoV-2 evolution or transmission. Nevertheless, such events could facilitate the emergence of fitness-enhancing mutations. To explore potential drivers of NTD deletion repair patterns, we characterized the viral phenotype of such markers in a surrogate in vitro system. Repair of the S:{Delta}H69/V70 deletion reduced viral infectivity, while simultaneous repair with S:{Delta}V143/Y145 led to lower fusogenicity. In contrast, individual S:{Delta}V143/Y145 repair enhanced both fusogenicity and susceptibility to neutralization by sera from vaccinated individuals. This work underscores the complex genotype-phenotype landscape of the spike NTD in SARS-CoV-2, which impacts viral biology, transmission efficiency, and immune escape potential, offering insights with direct relevance to public health, viral surveillance, and the adaptive mechanisms driving emerging variants.

evolutionary biology↗

bioRxiv2022

Centromere-associated retroelement evolution in Drosophila melanogaster reveals an underlying conflict

Centromeres are chromosomal regions essential for coordinating chromosome segregation during cell division. While centromeres are defined by the presence of a centromere-specific histone H3 variant rather than a particular DNA sequence, they are typically embedded in repeat-dense chromosomal genome regions. In many species, centromeres are associated with transposable elements, but it is unclear if these elements are selfish or if they play a role in centromere specification or function. Here we use Drosophila melanogaster as a model to understand the evolution of centromere-associated transposable elements. G2/Jockey-3 is a non-LTR retroelement in the Jockey clade and the only sequence shared by all centromeres. We study the evolution of G2/Jockey-3 using short and long read population genomic data to infer insertion polymorphisms across the genome. We combine estimates of the age, frequency, and location of insertions to infer the evolutionary processes shaping G2/Jockey-3 and its association with the centromeres. We find that G2/Jockey-3 is an active retroelement targeted by the piRNA pathway that is enriched in centromeres at least in part due to an insertion bias. We do not detect signatures of positive selection on any G2/Jockey-3 insertions that would suggest than individual copies are favored by natural selection. Instead, we infer that most insertions are neutral or weakly deleterious both inside and outside of the centromeres. Therefore, G2/Jockey-3 evolution is consistent with it being a selfish genetic element that targets centromeres. We propose that targeting centromeres helps active retroelements escape host defenses, as the unique centromeric chromatin may prevent targeting by the host silencing machinery. At the same time, centromeric TEs insertions may be tolerated or even beneficial if they also contribute to the transcriptional and chromatin environment. Thus, we suspect centromere-associated retroelements like G2/Jockey-3 reflect a balance between conflict and cooperation at the centromeres.

genomics↗

bioRxiv2021

Epistatic selection on a selfish Segregation Distorter supergene: drive, recombination, and genetic load

Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation to gain preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing alternative alleles. While at least two loci are important for male drive-- the driver and the target-- linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversion on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over and with wildtype chromosomes only via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly.

evolutionary biology↗

bioRxiv2019

Evolutionary success of a parasitic B chromosome rests on gene content

Supernumerary (B) chromosomes are dispensable genomic elements found in most kinds of eukaryotic genomes. Many show drive mechanisms that give them an advantage in transmission, but how they achieve it remains a mystery. The recent finding of protein-coding genes in B chromosomes has opened the possibility that their evolutionary success is based on their genetic content. Using a protocol based on mapping genomic DNA Illumina reads from B-carrying and B-lacking individuals on the coding sequences of de novo transcriptomes from the same individuals, we identified 25 protein-coding genes in the B chromosome of the migratory locust, 15 of which showed a full coding region. Remarkably, one of these genes (apc1) codes for the large subunit of the Anaphase Promoting Complex or Cyclosome (APC/C), an E3 ubiquitin ligase involved in the metaphase-anaphase transition. Sequence comparison of A and B chromosome gene paralogs showed that the latter show B-specific nucleotide changes, neither of which putatively impairs protein function. These nucleotide signatures allowed identifying B-derived transcripts in B-carrying transcriptomes, and demonstrated that they show about similar frequency as A-derived ones. Since B-carrying individuals show higher amounts of apc1 transcripts than B-lacking ones, the putatively higher amount of APC1 protein might induce a faster metaphase-anaphase transition in spite of orientation of the two B chromosome chromatids towards the same pole during metaphase, thus facilitating B chromosome non-disjunction. Therefore, apc1 is the first protein-coding gene uncovered in a B chromosome that might be responsible for B chromosome drive.\n\nSignificance StatementThe genome of the migratory locust harbors a parasitic chromosome that arose about 2 million years ago. It is widespread in natural populations from Asia, Africa, Australia and Europe, i.e. all continents where this species lives. The secret for such an extraordinary evolutionary success is unveiled in this report, as B chromosomes in this species contain active protein-coding genes whose transcripts might interfere with gene expression in the host genome (the A chromosomes), thus facilitating B chromosome mitotic and meiotic drive to provide the transmission advantage which grants its success. One of the B-chromosomal genes (apc1) codes for the large subunit of the Anaphase Promoting Complex or Cyclosome (APC/C) whose expression might provide a mechanistic explanation for B chromosome drive.

evolutionary biology↗