Biology subjects

Ruiz-Herrera, A.

Publications and source records attributed to Ruiz-Herrera, A..

12 recordsLinked to original sources

bioRxiv2026

Explaining the rapid evolution of mammalian meiotic recombination proteins

Meiotic recombination -- the exchange of genetic material between parental chromosomes during gamete production -- is critical for fertility, genome stability, and evolutionary adaptation. In eukaryotes, meiotic recombination is carried out by a deeply conserved molecular machinery. Despite this conservation, the sequences of proteins involved in meiotic recombination evolve at a remarkably high rate in mammalian species. Several biological processes have been proposed to explain this rapid evolution, but none have been quantitatively tested. In this study, we analyzed the variation in evolutionary rates of 100 recombination proteins across approximately 400 placental mammals. Our results show that this rapid evolution is primarily driven by lower levels of purifying selection compared to the rest of the proteome. We show that, although selective pressures exerted on recombination proteins are generally shared across mammals, a few recombination proteins exhibit strong variation in selective pressures. Contrary to previous hypotheses, we demonstrate that chromosome number and genome-wide recombination rates do not account for much of this variation. Instead, these variations are primarily associated with chromosome pairing and synapsis proteins, which tend to experience increased selective pressures throughout mammalian evolution, especially in large and long-lived species. This pattern probably reflects more intense selection for stability of chromosome pairing proteins in the oocytes of long-lived species, in which chromosomes sometimes need to stay paired for decades.

evolutionary biology↗

bioRxiv2025

A telomere to telomere phased genome assembly and annotation for the Australian central bearded dragon Pogona vitticeps

BackgroundThe central bearded dragon (Pogona vitticeps) is widely distributed in central eastern Australia and adapts readily to captivity. Among other attributes, it is distinctive because it undergoes sex reversal from ZZ genotypic males to phenotypic females at high incubation temperatures. Here, we report an annotated telomere to telomere phased assembly of the genome of a female ZW central bearded dragon. ResultsGenome assembly length is 1.75 Gbp with a scaffold N50 of 266.2 Mbp, N90 of 28.1 Mbp, 26 gaps and 42.2% GC content. Most (99.6%) of the reference assembly is scaffolded into 6 macrochromosomes and 10 microchromosomes, including the Z and W microchromosomes, corresponding to the karyotype. The genome assembly exceeds standard recommended by the Earth Biogenome Project (6CQ40): 0.003% collapsed sequence, 0.03% false expansions, 99.8% k-mer completeness, 97.9% complete single copy BUSCO genes and an average of 93.5% of transcriptome data mappable back to the genome assembly. The mitochondrial genome (16,731 bp) and the model rDNA repeat unit (length 9.5 Kbp) were assembled. Male vertebrate sex genes Amh and Amhr2 were discovered as copies in the small non-recombining region of the Z chromosome, absent from the W chromosome. This, coupled with the prior discovery of differential Z and W transcriptional isoform composition arising from pseudoautosomal sex gene Nr5a1, suggests that complex interactions between these genes, their autosomal copies and their resultant transcription factors and intermediaries, determines sex in the bearded dragon. ConclusionThis high-quality assembly will serve as a resource to enable and accelerate research into the unusual reproductive attributes of this species and for comparative studies across the Agamidae and reptiles more generally. Species TaxonomyEukaryota; Animalia; Chordata; Reptilia; Squamata; Iguania; Agamidae; Amphibolurinae; Pogona; Pogona vitticeps (Ahl, 1926) (NCBI:txid103695). Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/651798v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1a9d5fforg.highwire.dtl.DTLVardef@1206061org.highwire.dtl.DTLVardef@97acf7org.highwire.dtl.DTLVardef@1dc939d_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2025

Chromosome-level genomics and historical museum collections reveal new insights into the population structure and chromosome evolution of waterbuck

Advances in the sequencing and assembly of chromosome-level genome assemblies has enabled the study of non-model animals, providing further insights into the evolution of genomes and chromosomes. Here, we present the waterbuck (Kobus ellipsiprymnus) as an emerging model antelope for studying population dynamics and chromosome evolution. Antelope evolutionary history has been shaped by Robertsonian (Rb) fusions, with waterbuck also showing variation in karyotype due to two polymorphic Rb fusions. These polymorphisms are variable between and within the two recognised subspecies, the common and defassa waterbuck. To provide new insights into waterbuck evolution, we firstly assembled a chromosome-level genome assembly for the defassa subspecies using PacBio HiFi and Hi-C sequencing. We then utilised museum collections to carry out whole genome sequencing (WGS) of 24 historical waterbuck skins from both subspecies. Combined with a previous WGS dataset (n = 119), this represents the largest study of waterbuck populations to date. We found novel population structure and gene flow between waterbuck populations and regions across the genome with high genomic differentiation between the two subspecies. Several of these regions were found around the centromeres of fixed and polymorphic Rb fusions, exhibiting signatures of low recombination and local population structure. Interestingly, these regions contain genes involved in development, fertility, and recombination. Our results highlight the importance of assembling genomes to the chromosome-level, the utility and value of historical collections in sampling a wide-ranging species to uncover fine-scale population structure, and the potential impacts of Rb fusions on genomic differentiation and the recombination landscape.

evolutionary biology↗

bioRxiv2025

A single-cell multiomics roadmap of zebrafish spermatogenesis reveals regulatory principles of male germline formation

Spermatogenesis is the biological process by which male sperm cells (spermatozoa) are produced in the testes. Beyond facilitating the transmission of genetic information, spermatogenesis also provides a potential framework for inter- and transgenerational inheritance of gene-regulatory states. While extensively studied in mammals, our understanding of spermatogenesis in anamniotes remains limited. Here we present a comprehensive single-cell multiomics resource, combining single-cell RNA sequencing (scRNA-seq) and single-cell chromatin accessibility (scATAC-seq) profiling, with base-resolution DNA methylome (WGBS) analysis of sorted germ cell populations from zebrafish (Danio rerio) testes. We identify major germ cell types involved in zebrafish spermatogenesis as well as key drivers associated with these transcriptional states. Moreover, we describe localised DNA methylation changes associated with spermatocyte populations, as well as local and global changes in chromatin accessibility leading to chromatin compaction in spermatids. Notably, we identify loci that evade global chromatin compaction, and which remain accessible, suggesting a potential mechanism for the intergenerational transmission of gene-regulatory states. Overall, this high-resolution atlas of zebrafish spermatogenesis provides a valuable resource for studying vertebrate germ cell development, evolution, and epigenetic inheritance.

developmental biology↗

bioRxiv2024

Chromatin Environment-Dependent Effects of DOT1L on Gene Expression in Male Germ Cells

The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic and spike-in RNA-seq data, we deciphered the molecular role of DOT1L during mouse spermatogenesis and show that it has opposite effects on gene expression depending on chromatin environment. On the one hand, DOT1L represses autosomal genes that are devoid of H3K79me2 at their bodies and located in H3K27me3-rich/H3K27ac-poor environments. On the other hand, it activates the expression of genes enriched in H3K79me2 and located in H3K27me3-poor/H3K27ac-rich environments, predominantly X chromosome-linked genes, after meiosis I. This coincides with a significant increase in DOT1L expression at this stage and a genome-wide acquisition of H3K79me2, particularly on the sex chromosomes. Taken together, our results show that H3K79me2 positively correlates with male germ cell genetic program throughout spermatogenesis, with DOT1L predominantly inhibiting rather than activating gene expression. Interestingly, while DOT1L appears to directly regulate the (re)activation of X genes following meiotic sex chromosome inactivation, it also controls the timely expression of (autosomal) differentiation genes during spermatogenesis.

molecular biology↗

bioRxiv2024

A punctuated burst of massive genomic rearrangements by chromosome shattering and the origin of non-marine annelids

The genomic basis of cladogenesis and adaptive evolutionary change has intrigued biologists for decades. Here, we show that the tectonics of genome evolution in clitellates, a clade composed of most freshwater and all terrestrial species of the phylum Annelida, is characterised by extensive genome-wide scrambling that resulted in a massive loss of macrosynteny between marine annelids and clitellates. These massive rearrangements included the formation of putative neocentromeres with newly acquired transposable elements and preceded a further period of genome-wide reshaping events, potentially triggered by the loss of genes involved in genome stability and homeostasis of cell division. Notably, while these rearrangements broke short-range interactions observed between Hox genes in marine annelids, they were reformed as long-range interactions in clitellates. Our findings reveal extensive genomic reshaping in clitellates at both the linear (2D) and three-dimensional (3D) levels, suggesting that, unlike in other animal lineages where synteny conservation constrains structural evolution, clitellates exhibit a remarkable tolerance for chromosomal rearrangements. Our study thus suggests that the genomic landscape of Clitellata resulted from a rare burst of genomic changes that ended a long period of stability that persists across large phylogenetic distances.

evolutionary biology↗

bioRxiv2023

Both phenotypic and genotypic sex influence sex chromosome dosage compensation in a sex reversing lizard

BackgroundLizards have sex determination systems that can differ between even closely related species. These include XY and ZW systems, and thermolabile systems where genes and temperature interact to determine sex. The eastern three-lined skink (Bassiana duperreyi) has a differentiated XY sex determination system, in which low temperature incubation during development can cause female to male sex reversal, producing XX males. This provides a unique opportunity to investigate how genotype and sexual phenotype affect dosage compensation. ResultsHere, we present a draft genome assembly of the Eastern three-lined skink generated from nanopore sequencing. We also generated transcriptomes from brain and heart tissue of normal adult males and females, along with brain tissue of sex-reversed XX males. We observed partial dosage compensation between XX females and XY males in both brain and heart, with median gene expression from the X in normal males being 0.7 times that of normal females. In brain of sex reversed XX males the median X chromosome output matched that of the normal XX female level, and not that of normal XY males. ConclusionsPartial dosage compensation in the Eastern three-lined skink is similar to several other species of lizard. However, here for the first time we describe dosage compensation in a lizard with natural sex reversal, and show that in sex reversed individuals dosage compensation of the X chromosome follows genotypic sex and not phenotypic sex.

genomics↗

bioRxiv2023

Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample

Ancient DNA (aDNA) sequencing analysis typically involves alignment to a modern reference genome assembly from a related species. Since aDNA molecules are fragmentary, these alignments yield information about small-scale differences, but provide no information about larger features such as the chromosome structure of ancient species. We report the genome assembly of a female Late Pleistocene woolly mammoth (Mammuthus primigenius) with twenty-eight chromosome-length scaffolds, generated using mammoth skin preserved in permafrost for roughly 52,000 years. We began by creating a modified Hi-C protocol, dubbed PaleoHi-C, optimized for ancient samples, and using it to map chromatin contacts in a woolly mammoth. Next, we developed "reference-assisted 3D genome assembly," which begins with a reference genome assembly from a related species, and uses Hi-C and DNA-Seq data from a target species to split, order, orient, and correct sequences on the basis of their 3D proximity, yielding accurate chromosome-length scaffolds for the target species. By means of this reference-assisted 3D genome assembly, PaleoHi-C data reveals the 3D architecture of a woolly mammoth genome, including chromosome territories, compartments, domains, and loops. The active (A) and inactive (B) genome compartments in mammoth skin more closely resemble those observed in Asian elephant skin than the compartmentalization patterns seen in other Asian elephant tissues. Differences in compartmentalization between these skin samples reveal sequences whose transcription was potentially altered in mammoth. We observe a tetradic structure for the inactive X chromosome in mammoth, distinct from the bipartite architecture seen in human and mouse. Generating chromosome-length genome assemblies for two other elephantids (Asian and African elephant), we find that the overall karyotype, and this tetradic Xi structure, are conserved throughout the clade. These results illustrate that cell-type specific epigenetic information can be preserved in ancient samples, in the form of DNA geometry, and that it may be feasible to perform de novo genome assembly of some extinct species.

genomics↗

bioRxiv2023

Incomplete transcriptional dosage compensation of vertebrate sex chromosomes is balanced by post-transcriptional compensation.

Heteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between the sexes, and with the autosomes. Mammalian X chromosome inactivation was long thought to imply a critical need for dosage compensation in vertebrates. However, the universal importance of sex chromosome dosage compensation was questioned by mRNA abundance measurements that demonstrated sex chromosome transcripts are neither balanced between the sexes or with autosomes in monotreme mammals or birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females that correlate with differential loading of histone modifications, and confirm that transcripts of Z genes are unbalanced between males and females also in chicken. However, we found that in both species, median male to female protein abundance ratios were 1:1, implying an additional level of post-transcriptional control. We conclude that parity of sex chromosome output is achieved in birds, as well as all mammal groups, by a combination of transcriptional and post-transcriptional control, consistent with an essential role for sex chromosome dosage compensation in vertebrates.

evolutionary biology↗

bioRxiv2023

Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials

In eutherian mammals, hundreds of programmed DNA double-strand breaks (DSBs) are generated at the onset of meiosis. The DNA damage response is then triggered. Although the dynamics of this response is well studied in eutherian mammals, recent findings have revealed different patterns of DNA damage signaling and repair in marsupial mammals. To better characterize these differences, here we analyzed synapsis and the chromosomal distribution of meiotic DSBs markers in three different marsupial species (Thylamys elegans, Dromiciops gliorides, and Macropus eugenii) that represent South American and Australian Orders. Our results revealed inter-specific differences in the chromosomal distribution of DNA damage and repair proteins, which were associated with differing synapsis patterns. In the American species T. elegans and D. gliroides, synapsis progressed exclusively from the chromosomal ends towards interstitial regions. This was accompanied by sparse H2AX phosphorylation, mainly accumulating at chromosomal ends, which appeared conspicuously polarized in a bouquet configuration at early stages of prophase I. Accordingly, RAD51 and RPA were mainly localized at chromosomal ends throughout prophaseI in both American marsupials, likely resulting in reduced recombination rates at interstitial positions. In sharp contrast, synapsis initiated at both interstitial and distal chromosomal regions in the Australian representative M. eugenii, {gamma}H2AX had a broad nuclear distribution, and RAD51 and RPA foci displayed an even chromosomal distribution. Given the basal evolutionary position of T. elegans, it is likely that the meiotic features reported in this species represent an ancestral pattern in marsupials and that a shift in the meiotic program occurred after the split of D. gliroides and the Australian marsupial clade. Our results open intriguing questions about the regulation and homeostasis of meiotic DSBs in marsupials. The low recombination rates observed at the interstitial chromosomal regions in American marsupials can result in the formation of large linkage groups, thus having an impact in the evolution of their genomes.

genetics↗

bioRxiv2021

Microchromosomes are building blocks of bird, reptile and mammal chromosomes

Microchromosomes, once considered unimportant shreds of the chicken genome, are gene rich elements with a high GC content and few transposable elements. Their origin has been debated for decades. We used cytological and whole genome sequence comparisons, and chromosome conformation capture, to trace their origin and fate in genomes of reptiles, birds and mammals. We find that microchromosomes as well as macrochromosomes are highly conserved across birds, and share synteny with single small chromosomes of the chordate amphioxus, attesting to their origin as elements of an ancient animal genome. Turtles and squamates (snakes and lizards) share different subsets of ancestral microchromosomes, having independently lost microchromosomes by fusion with other microchromosomes or macrochromosomes. Patterns of fusions were quite different in different lineages. Cytological observations show that microchromosomes in all lineages are spatially separated into a central compartment at interphase and during mitosis and meiosis. This reflects higher interaction between microchromosomes than with macrochromosomes, as observed by chromosome conformation capture, and suggests some functional coherence. In highly rearranged genomes fused microchromosomes retain most ancestral characteristics, but these may erode over evolutionary time; surprisingly de novo microchromosomes have rapidly adopted high interaction. Some chromosomes of early branching monotreme mammals align to several bird microchromosomes, suggesting multiple microchromosome fusions in a mammalian ancestor. Subsequently multiple rearrangements fueled the extraordinary karyotypic diversity of therian mammals. Thus microchromosomes, far from being aberrant genetic elements, represent fundamental building blocks of amniote chromosomes, and it is mammals, rather than reptiles, that are atypical. Significance StatementGenomes of birds and reptiles, but not mammals, consist of a few large chromosomes and many tiny microchromosomes. Once considered unimportant shreds of the genome, microchromosomes are gene rich and highly conserved among bird and reptiles, and share homology with one or more of the tiny chromosomes of an invertebrate that diverged from the vertebrate lineage 684 million years ago. Microchromosomes interact strongly and crowd together at the centre of cells, suggesting functional coherence. Many microchromosomes have been lost independently in turtles, snakes and lizards as they have fused with each other, or with larger chromosomes. In mammals they have completely disappeared, yet some chromosomes of the basal platypus line up with several microchromosomes, suggesting that they are the building blocks of the atypically variable chromosomes of mammals.

genomics↗

bioRxiv2018

Genetic distance between complex repeats

Complex nucleotide or aminoacid repeats with long units play an important role in proteins. The evolutionary analysis of these variants is challenging due to genetic diversity within repeat units as well as variability in the arrangement of different units along the repeat sequence. Here we present a new approach for the computation of genetic distances between complex repeats. This method takes into account evolutionary processes including point mutations, insertions and deletions of repeat units, as well as duplication of single units. We provide an algorithm for the computation of these distances along with the corresponding global pairwise alignment of repeats. As an example, we apply our approach to the evolution of repeat units in the highly polymorphic zinc-finger repeat domain of the PRDM9 protein across wild populations of house mice. This approach opens the way for new insights into the evolutionary history of polymorphic repeats.

bioinformatics↗