Biology subjects

Barbash, D.

Publications and source records attributed to Barbash, D..

7 recordsLinked to original sources

bioRxiv2026

A transposon origin of large tandem repeats in the butterfly Papilio bianor

Without single centromeres, holocentric chromosomes do not accumulate repetitive DNA in the same way as their monocentric ancestors. In holocentric butterflies and moths, large tandem repeats are rare compared to other insects with monocentric chromosomes. We discover in the butterfly Papilio bianor that nearly half of its chromosomes have large tandem repeats composed entirely of transposons. These transposon arrays are formed by concerted expansion of multiple families, often locked together as a single repeating unit of 100kb-200kb in length. On Hi-C contact maps, transposon arrays partition chromosomes into distinct "arms" and insulate the inter-arm contact. Chromosomes with transposon arrays are also more compact than those without the arrays. In male meiosis, transposon arrays facilitate double crossovers, likely by reducing crossover interference between the flanking arms. As a result, chromosomes with transposon arrays exhibit increased recombination rates. Taken together, we demonstrate that large tandem repeats can affect multiple aspects of holocentric chromosomes, and in many ways, the effects resemble those of centromeres in monocentric organisms.

evolutionary biology↗

bioRxiv2023

The structure of simple satellite variation in the human genome and its correlation with centromere ancestry

Although repetitive DNA forms much of the human genome, its study is challenging due to limitations in assembly and alignment of repetitive short-reads. We have deployed k-Seek, software that detects tandem repeats embedded in single reads, on 2,504 human genomes from the 1,000 Genomes Project to quantify the variation and abundance of simple satellites (repeat units < 20 bp). We find that homopolymers and the Human Satellite 3 monomer make up the largest portions of simple satellite content in humans (mean of [~]19 Mb combined). We discovered[~]50,000 rare tandem repeats that are not detected in the T2T-CHM13v2.0 assembly, including undescribed variants of telomeric- and centromeric repeats. We find broad homogeneity of the most abundant repeats across populations, except for AG-rich repeats that are more abundant in African individuals. We also find cliques of highly similar AG- and AT-rich satellites that are interspersed and form higher-order structures that covary in copy number across individuals, likely through concerted amplification via unequal exchange. Finally, we use centromere-linked polymorphisms to estimate centromeric genetic relatedness between individuals and find a strong predictive relationship between centromeric lineages and centromeric simple satellite abundances. In particular, Human Satellite 2 and Human Satellite 3 abundances correlate with clusters of centromeric ancestry on chromosome 16 and chromosome 9, with some clusters structured by population. These results provide new descriptions of the population dynamics that underlie the evolution of simple satellites in humans.

genomics↗

bioRxiv2023

Testing a candidate meiotic drive locus identified by pool sequencing

Meiotic drive biases the transmission of alleles in heterozygous individuals, such that Mendels law of equal segregation is violated. Most examples of meiotic drive have been discovered over the past century based on causing sex-ratio distortion or the biased transmission of easily scoreable genetic markers that were linked to drive alleles. More recently, several approaches have been developed that attempt to identify distortions of Mendelian segregation genome-wide. Here we test a candidate female meiotic drive locus in Drosophila melanogaster, identified previously as causing a [~]54:46 distortion ratio using sequencing of large pools of backcross progeny. We inserted fluorescent visible markers near the candidate locus and scored transmission in thousands of individual progeny. We observed a small but significant deviation from the Mendelian expectation, however it was in the opposite direction to that predicted based on the original experiments. We discuss several possible causes of the discrepancy between the two approaches, noting that subtle viability effects are particularly challenging to disentangle from potential small-effect meiotic drive loci. We conclude that pool sequencing approaches remain a powerful method to identify candidate meiotic drive loci, but that genotyping of individual progeny at early developmental stages may be required for robust confirmation.

genetics↗

bioRxiv2022

Testing the Drosophila maternal haploid gene for functional divergence and a role in hybrid incompatibility

Crosses between D. simulans females and D. melanogaster males produce viable F1 sons and poorly viable F1 daughters. Unlike most hybrid incompatibilities, this hybrid incompatibility violates Haldanes rule, the observation that incompatibilities preferentially affect the heterogametic sex. Further, it is important to understand fully the genetic basis of this incompatibility because the causal allele in D. melanogaster is a large species-specific block of complex satellite DNA on its X chromosome known as the 359-bp satellite, rather than a protein-coding locus. The causal allele(s) in D. simulans are unknown but likely involve maternally expressed genes or factors since the F1 females die during early embryogenesis. The maternal haploid (mh) gene is an intriguing candidate because it is expressed maternally and its protein product localizes to the 359-bp repeat. We found that this gene has diverged extensively between D. melanogaster and D. simulans. This observation led to the hypothesis that D. melanogaster mh may have co-evolved with the 359-bp repeat, and that hybrid incompatibility thus results from the absence of a co-evolved mh allele in D. simulans. We tested for functional divergence of mh by creating matched transformants of D. melanogaster and D. simulans orthologs in both D. melanogaster and D. simulans strains. Surprisingly, we find that D. simulans mh fully complements the female sterile phenotype of D. melanogaster mh mutations. Contrary to our hypothesis, we find no evidence that adding a D. melanogaster mh gene to D. simulans increases hybrid viability.

evolutionary biology↗

bioRxiv2021

Inferred Clades of Transposable Elements in Drosophila Suggest Co-evolution with piRNAs

Transposable elements (TEs) are self-replicating "genetic parasites" ubiquitous to eukaryotic genomes. In addition to conflict between TEs and their host genomes, TEs of the same family are in competition with each other. They compete for the same genomic niches while experiencing the same regime of copy-number selection. This suggests that competition among TEs may favor the emergence of new variants that can outcompete their ancestral forms. To investigate the sequence evolution of TEs, we developed a method to infer clades: collections of TEs that share SNP variants and represent distinct TE family lineages. We applied this method to a panel of 85 Drosophila melanogaster genomes and found that the genetic variation of several TE families shows significant population structure that arises from the population- specific expansions of single clades. We used population genetic theory to classify these clades into younger versus older clades and found that younger clades are associated with a greater abundance of sense and antisense piRNAs per copy than older ones. Further, we find that the abundance of younger, but not older clades, is positively correlated with antisense piRNA production, suggesting a general pattern where hosts preferentially produce antisense piRNAs from recently active TE variants. Together these findings suggest a pattern whereby new TE variants arise by mutation and then increase in copy number, followed by the host producing antisense piRNAs that may be used to silence these emerging variants.

genetics↗

bioRxiv2019

Divergence of piRNA pathway proteins affects piRNA biogenesis but not TE transcript level

In metazoan germlines, the piRNA pathway acts as a genomic immune system, employing small RNA-mediated silencing to defend host DNA from the harmful effects of transposable elements (TEs). In response to dynamic changes in TE content, host genomes are proposed to alter the piRNAs that they produce in order to silence the most active TE families. Surprisingly, however, piRNA pathway proteins, which execute piRNA biogenesis and enforce silencing of targeted sequences, also evolve rapidly and adaptively in animals. If TE silencing evolves through changes in piRNAs, what necessitates changes in piRNA pathway proteins? Here we used interspecific complementation to test for functional differences between Drosophila melanogaster and D. simulans alleles of three adaptively evolving piRNA pathway proteins: Armitage, Aubergine and Spindle-E. Surprisingly, we observed interspecific divergence in the regulation of only a handful of TE families, which were more robustly silenced by the heterospecific piRNA pathway protein. This suggests that positive selection does not act on piRNA effector proteins to enhance their function in TE repression, but rather that TEs may evolve to "escape" silencing by homospecific alleles. We also discovered that D. simulans alleles of aub and armi exhibit enhanced off-target effects on host transcripts in a D. melanogaster background, suggesting the avoidance of genomic auto-immunity as a critical target of selection. Our observations suggest that piRNA effector proteins are subject to an evolutionary trade-off between defending the host genome from the harmful effect of TEs while also minimizing friendly fire against host genes. Author SummaryTransposable elements are mobile fragments of selfish DNA that burden host genomes with deleterious mutations and incite genome instability. Host cells employ a specialized small-RNA mediated silencing pathway, the piRNA pathway, to act as a genomic immune system suppressing the mobilization of TEs. Changes in genomic TE content are met with rapid changes in the piRNA pool, thereby maintain host control over transposition. However, piRNA pathway proteins--which enact piRNA biogenesis and silence target TEs--also evolve adaptively. To isolate forces that underlie this adaptive evolution, we examined functional divergence between two Drosophila species for three adaptively evolving piRNA pathway proteins. To our surprise, we found very few differences in TE regulation, suggesting that evolution has not generally acted to enhance control of TE parasites. Rather, we discovered interspecific differences in the regulation of host mRNAs for two proteins, which suggested that proteins evolve to avoid off-target silencing of host transcripts. We propose that the avoidance of such "genomic autoimmunity" is an important and underappreciated force driving the adaptive evolution of piRNA proteins.

evolutionary biology↗

bioRxiv2017

Lhr and Hmr are required for sister chromatid detachment during anaphase but not for centromere function

Crosses between Drosophila melanogaster females and Drosophila simulans males produce hybrid sons that die at the larval stage. This hybrid lethality is suppressed by loss-of-function mutations in the D. melanogaster Hybrid male rescue (Hmr) or in the D. simulans Lethal hybrid rescue (Lhr) genes. Previous studies have shown that Hmr and Lhr interact with heterochromatin proteins and suppress expression of transposable elements within D. melanogaster. It also has been proposed that Hmr and Lhr function at the centromere. We examined mitotic divisions in larval brains from Hmr and Lhr single mutants and Hmr; Lhr double mutants in D. melanogaster. In none of the mutants did we observe defects in metaphase chromosome alignment or hyperploid cells, which are hallmarks of centromere or kinetochore dysfunction. In addition, we found that Hmr-HA and Lhr-HA do not localize to centromeres either during interphase or mitotic division. However, all mutants displayed anaphase bridges and chromosome aberrations resulting from the breakage of these bridges, predominantly at the euchromatin-heterochromatin junction. The few dividing cells present in hybrid males showed irregularly condensed chromosomes with fuzzy and often closely apposed sister chromatids. Despite this defect in condensation, chromosomes in hybrids managed to align on the metaphase plate and undergo anaphase. We conclude that there is no evidence for a centromeric function of Hmr and Lhr within D. melanogaster nor for a centromere defect causing hybrid lethality. Instead we find that Hmr and Lhr are required in D. melanogaster for detachment of sister chromatids during anaphase.

genetics↗