Whole-genome sequencing across space and time reveals impact of population decline and reduced gene flow in Florida Scrub-Jays

Nguyen, T. N.; Cosgrove, E. J.; Chen, N.; Lehr, N.; Lokey, M.; Beaudry, F. E. G.; Fitzpatrick, S. W.; Miller, K. E.; Fitzpatrick, J. W.; Clark, A. G.

doi:10.1101/2024.11.05.622154

bioRxiv · 10.1101/2024.11.05.622154

Whole-genome sequencing across space and time reveals impact of population decline and reduced gene flow in Florida Scrub-Jays

Nguyen, T. N.·Cosgrove, E. J.·Chen, N.·Lehr, N.·Lokey, M.·Beaudry, F. E. G.·Fitzpatrick, S. W.·Miller, K. E.·Fitzpatrick, J. W.·Clark, A. G.

View original source ↗Export metadata ↓

Abstract

Whole-genome sequence data is proving to be highly informative about the past demography of free-living populations, and in the context of endangered species, it can provide a quantification of the genetic risk posed by reduced genetic diversity and inbreeding. Prior to 1920, the Florida scrub-jay (Aphelocoma coerulescens) had been widespread across Florida, but with the expansion of agriculture and human habitation, its population has declined by 95%, resulting in fragmentation into semi-isolated subpopulations. By sequencing 241 individuals sampled from five different regions and across two time points, this study quantifies a greater magnitude of loss of genetic diversity and greater levels of inbreeding in smaller and more isolated subpopulations. Consistent with population genetics theory, reduction in population size results in a dramatic loss of rare alleles, skewing the site frequency spectrum far from the expected equilibrium. Increased inbreeding in the smaller, more remote subpopulations is especially evident in the increased size and number of runs of homozygosity. The Florida scrub-jay displays limited dispersal, and habitat fragmentation has greatly reduced the magnitude of gene flow in the past 30 years, resulting in further decline of genetic diversity, especially in the peripheral populations. Analysis of these data is informative in guiding conservation efforts to retain genetic diversity and minimize the consequences of inbreeding in the Florida scrub-jay. HighlightsO_LIFive regional populations show distinct degrees of population isolation and decline. C_LIO_LIThere has been commensurate loss of genetic diversity, skewed site frequency spectra, reduced migration, and increased inbreeding (FROH). C_LIO_LIAs many state-wide populations decline, the smaller, more remote populations provide a glimpse into the future and a testbed for remediation approaches. C_LI

Explore related subjects

genomics Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Nguyen, T. N., Cosgrove, E. J., Chen, N., Lehr, N., Lokey, M., Beaudry, F. E. G., Fitzpatrick, S. W., Miller, K. E., Fitzpatrick, J. W., Clark, A. G.. 2024-11-08. Whole-genome sequencing across space and time reveals impact of population decline and reduced gene flow in Florida Scrub-Jays. https://doi.org/10.1101/2024.11.05.622154

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

Somatic mosaicism contributes to genomic variation, yet postzygotic structural variants remain under-characterized. We performed long- and short-read WGS from multiple individuals (n=47 normal tissues; n=168 samples) and identified mosaic structural variants in all individuals and germ layers, impacting a median 285.2 kb/genome. Nearly half of breakpoints were independently validated, with tissue distributions reflecting both early and late developmental origins. Most mosaic variants were repeat-mediated and 8.3% overlapped functional elements, an enrichment compared to germline variants. To extend these analyses in samples where long-read sequencing is infeasible, we measured repeat alterations from short-read sequencing, recapitulating mosaic tissue-specific differences. We characterized tumor- and tissue- specific variation in repeats across 15 cancer types and found tumor-related repeat variation to be similar in scale to that of normal mosaic variation. Tracking repeat changes in cell-free DNA provided a noninvasive approach for tumor monitoring. Our analyses revealed widespread repeat-driven structural variation in health and disease.

genomics↗

bioRxiv2026

RNA isoform-resolved multiplexed sequencing with bioorthogonal barcoding

RNA isoform dysregulation drives disease pathogenesis and is the target of FDA-approved splice-switching therapeutics. However, multiplexed sequencing methods discard splice junction information because only 3' termini are barcoded and counted. Here, we repurpose acylation and click chemistries to conjugate bioorthogonal barcodes (bobcodes) directly onto multiple internal positions along cellular RNAs. Bobcoded RNAs from multiple samples are pooled for multiplexed cDNA synthesis, during which reverse transcriptase switches from each RNA template onto its tethered bobcode with greater than 99% accuracy in species mixing experiments. Bobcode attachment intervals set cDNA insert sizes without a library fragmentation step, and priming with poly(dT) or random hexamers selects between 3'-end counting and full-length isoform capture. A bioorthogonal barcode-sequencing (BOB-seq v0.1) drug screen identifies transcriptome-wide on- and off-target RNA splicing effects and outperforms existing multiplexing RNA sequencing methods in workflow simplicity, sample-to-sample variability, and barcoding accuracy. Bobcodes add isoform resolution to scalable multiplexed RNA sequencing.

genomics↗

bioRxiv2026

Structural polymorphism and population-variable coding capacity of HERV-K(HML-2) in human pangenomes

Approximately 8% of the human genome is derived from ancient retroviral infections. The most recently integrated of these endogenous retroviruses is the HERV-K(HML-2) clade, whose expression has been associated with cancer, amyotrophic lateral sclerosis, and embryogenesis. Studies of HERV expression, particularly HML-2, have relied predominantly on short-read sequencing. However, the high similarity among HML-2 proviruses prevents many short reads from being assigned uniquely to individual loci. We therefore compared haplotype-resolved long-read genome assemblies from 292 donors to resolve variation in proviral structure and coding capacity. Several loci previously thought to be fixed were structurally polymorphic. Tandem arrays occurred at 13 loci and contained up to six proviral copies in a single array. At 8q11.23, we identified a previously undescribed full-length provirus in one haplotype. All 583 other haplotypes carried a solo-LTR. We found that standard reference genomes failed to represent the coding capacity retained in many individuals, whose proviruses contained intact open reading frames despite disruptive mutations in the reference sequences. Short-read genotypes left 32.5% of the tested donor-variant pairs unresolved at sites associated with viral reading frames. These findings show why HML-2 expression must be interpreted in the context of the structural and coding alleles each individual carries.

genomics↗