Biology subjects

Rocha, J. L.

Publications and source records attributed to Rocha, J. L..

4 recordsLinked to original sources

bioRxiv2026

Comparative genomics of Tandem Repeat variation in apes

Tandem repeats (TRs) are highly mutable DNA elements that influence gene regulation1, protein structure2, and disease3. Until recently, their repetitive nature has hindered accurate TR sequencing and genotyping, resulting in sparse comparative data across species. In addition, we lack population-aware approaches to analyze TR conservation, divergence, and mutational dynamics. Here, leveraging telomere-to-telomere primate genomes and long-read data from 46 humans and 23 chimpanzees, we constructed a catalog of homologous TR loci, and developed an analytical framework to jointly analyze TR variation within- and between-species. Across primates, TR diversity and conservation vary strongly with genomic context, with coding and 5 UTR TRs exhibiting reduced polymorphism and constraint across species, consistent with stabilizing selection. Yet, while TRs are depleted in coding sequence, they are enriched in 5 UTRs, suggesting functional roles that outweighs mutational risks. TR heterozygosity varies across motif lengths and is concordant with both evolutionary and trio-based mutation rate estimates4. Introducing an HKA-like approach to control for locus-specific mutation rates, we identified TRs with signatures of directional and balancing selection. These candidates are significantly enriched in genes involved in nervous system development and synaptic function, highlighting TRs as potential contributors to neural evolution. Further, TR divergence correlates with gene expression divergence, particularly for promoter-related TRs and expression in organoids related to neurodevelopment, implicating a subset of regulatory TRs as candidates for adaptive expression evolution. Finally, trait-associated TRs display longer alleles and higher diversity in humans compared to chimpanzees, consistent with lineage-specific runaway mutations and/or directional selection5. Together, our results establish a comparative framework for TR evolutionary analyses, revealing how mutational processes and selection jointly shape repeat variation, and supporting their role as both conserved functional elements and as drivers of evolutionary innovation.

evolutionary biology↗

bioRxiv2025

Ancient convergence with prokaryote defense and recent adaptations to lentiviruses in primates characterize the ancestral immune factors SAMD9s

Human SAMD9 and SAMD9L are duplicated genes that encode innate immune proteins restricting poxviruses and lentiviruses, such as HIV, and implicated in life-threatening genetic diseases and cancer. Here, we combined structural similarity searches, phylogenetics and population genomics with experimental assays of SAMD9/9L functions to resolve the evolutionary and functional dynamics of these immune proteins, spanning from prokaryotes to primates. We discovered structural analogs of SAMD9/9L in the anti-bacteriophage defense system Avs, resulting from convergent evolution. Further, the predicted nuclease active site was conserved in bacterial analogs and was essential for cell death functions, suggesting a fundamental role in defense across different life kingdoms. Despite this ancestral immunity, we identified genomic signatures of evolutionary arms-races in mammals, with remarkable gene copy number variations targeted by natural selection. We further unveiled that the absence of SAMD9 in bonobos corresponds to a recent gene loss still segregating in the population. Finally, we found that chimp and bonobo SAMD9Ls have enhanced anti-HIV-1 functions, and that bonobo-specific SAMD9L polymorphisms confer increased anti-HIV-1 activity to human SAMD9L without compromising its effect on cell translation. These SAMD9/9L adaptations likely resulted from strong viral selective pressures, including by primate lentiviruses, and could contribute to lentiviral resistance in bonobos. Altogether, this study elucidates the interplay between ancient immune convergence across kingdoms and species-specific adaptations within the Avs9 and SAMD9/9L antiviral shared immunity. Significance statementThe SAMD9 gene family encodes antiviral factors of poxviruses and lentiviruses/HIV and is implicated in genetic diseases. Here, we found strong structural similarity with proteins from the Avs anti-bacteriophage system and uncovered ancient functional convergence in immune strategies between prokaryotes and metazoans. Within mammals, and more importantly in primates, we describe a highly dynamic evolutionary history of the SAMD9 gene family that underwent adaptive episodic gene losses. Unlike humans and chimps, some bonobos lack the SAMD9 gene entirely. Bonobos and chimps also possess unique variants of SAMD9L enhancing anti-HIV-1 activity without compromising cell functions, suggesting super-restrictors. This could also participate in shaping SIVcpz evolution and contribute to the absence of lentivirus-infected bonobos. Overall, the seeming dichotomy between the ancient evolutionary convergence in different kingdoms and recent functional adaptation within primates highlights the arms-races between key immune defense systems and viruses. This study paves the way for evolutionary medicine, where evolutionary-based discoveries may have application to human health, providing a deeper understanding of how the immune system adapts to fight viral infections over billion years of evolution.

evolutionary biology↗

bioRxiv2024

TRACKing Tandem Repeats: a customizable pipeline for identification and cross-species comparisons

SummaryTRACK is a user-friendly command-line pipeline designed to consolidate the discovery and comparison of tandem repeats (TRs) across species. TRACK facilitates the cataloging and filtering of TRs based on reference genomes or T2T transcripts, and applies reciprocal LiftOver and sequence alignment methods to identify putative homologous TRs between species. For further streamlined analyses, TRACK can be used to genotype TRs and subsequently estimate and plot basic population genetic statistics. By integrating existing tools into one integrated workflow, TRACK enhances TR analysis accessibility and reproducibility, while offering flexibility for the user. AvailabilityThe TRACK toolkit with step-by-step tutorial is freely available at https://github.com/caroladam/track.

genomics↗

bioRxiv2023

Genetic basis of aposematic coloration in a mimetic radiation of poison frogs

The evolution of mimicry in a single species or population has rippling inter and intraspecific effects across ecological communities, providing a fascinating mechanism of phenotypic diversification. In this study we present the first identification of genes underlying Mullerian mimicry in a vertebrate, the Peruvian mimic poison frog, Ranitomeya imitator. We sequenced 124 R. imitator exomes and discovered loci with both strong divergence between different mimetic morphs and phenotypic associations within an intraspecific admixture zone, implicating mc1r, asip, bsn, retsat, and krt8.2 in the evolution of mimetic color phenotypes. We confirmed these associations for most candidate genes through linkage mapping in a lab-reared pedigree. We also sequenced transcriptomes from the model species, allowing tests for introgression and revealing that the mimetic resemblance between R. imitator and the models evolved independently. Selection analyses of the candidate genes show that the mimicry phenotypes likely have evolved through selective sweeps acting on polygenic variation. Our results suggest that the evolutionary origins and molecular mechanisms underlying mimicry phenotypes in vertebrates may be radically different from those previously documented in invertebrates such as the iconic Heliconius butterfly mimicry complex. One Sentence SummaryMullerian mimicry evolved through independent selective sweeps on color and pattern loci in the mimic poison frog.

evolutionary biology↗