Biology subjects

Fuller, Z. L.

Publications and source records attributed to Fuller, Z. L..

8 recordsLinked to original sources

bioRxiv2023

Patterns of recombination in snakes reveal a tug of war between PRDM9 and promoter-like features

In vertebrates, there are two known mechanisms by which meiotic recombination is directed to the genome: in humans, mice, and other mammals, recombination occurs almost exclusively where the protein PRDM9 binds, while in species lacking an intact PRDM9, such as birds and canids, recombination rates are elevated near promoter-like features. To test if PRDM9 also directs recombination in non-mammalian vertebrates, we focused on an exemplar species, the corn snake (Pantherophis guttatus). Unlike birds, this species possesses a single, intact PRDM9 ortholog. By inferring historical recombination rates along the genome from patterns of linkage disequilibrium and identifying crossovers in pedigrees, we found that PRDM9 specifies the location of recombination events outside of mammals. However, we also detected an independent effect of promoter-like features on recombination, which is more pronounced on macrothan microchromosomes. Thus, our findings reveal that the uses of PRDM9 and promoter-like features are not mutually-exclusive, and instead reflect a tug of war, which varies in strength along the genome and is more lopsided in some species than others. One sentence summaryWhile the localization of meiotic recombination in vertebrates was previously thought to occur using one of two distinct mechanisms, our analysis of recombination in corn snakes reveals that they and likely other vertebrates use both of these mechanisms.

evolutionary biology↗

bioRxiv2022

Genomics of Natural Populations: Gene Conversion Events Reveal Selected Genes within the Inversions of Drosophila pseudoobscura

When adaptive phenotypic variation or QTLs map within an inverted segment of a chromosome, researchers often despair because it is thought that the suppression of crossing over will prevent the discovery of selective target genes that contribute to the establishment of the rearrangement. If an inversion polymorphism is old enough, then the accumulation of gene conversion tracts offers the promise that QTLs or selected loci within inversions can be mapped. This study uses the inversion polymorphism of Drosophila pseudoobscura as a model system to show that gene conversion analysis is a useful tool for mapping selected loci within inversions. D. pseudoobscura has over 30 different chromosomal arrangements on the third chromosome (Muller C) in natural populations and their frequencies vary with changes in environmental habitats. Statistical tests of five D. pseudoobscura gene arrangements identified outlier genes within inverted regions based on local clusters of fixed SNP differences. These outlier genes also had potentially heritable variation, either fixed amino acid differences or differential expression patterns among arrangements. Here, we use genome sequences of the inverted third chromosome (Muller C) to infer 98,443 gene conversion tracts for a total coverage of 142 Mb or 7.2 x coverage of the 19.7 Mb chromosome. We estimated gene conversion tract coverage in the 2,668 genes on Muller C and tested whether the number of genes with significantly low coverage was the same for outlier versus non-outlier loci.. Genes with low gene conversion tract coverage were more frequent in the outlier class than the non-outlier class suggesting that selection removes exchanged DNA from the outlier genes more often than non-outlier genes. These data support the hypothesis that the pattern and organization of genetic diversity on the third chromosome in D. pseudoobscura is consistent with the capture of locally adapted combinations of alleles prior to inversion mutation events.

evolutionary biology↗

bioRxiv2022

Relating pathogenic loss-of function mutations in humans to their evolutionary fitness costs

Causal loss-of-function (LOF) variants for Mendelian and severe complex diseases are enriched in "mutation intolerant" genes. We show how such observations can be interpreted in light of a model of mutation-selection balance, and use the model to relate the pathogenic consequences of LOF mutations at present-day to their evolutionary fitness effects. To this end, we first infer posterior distributions for the fitness costs of LOF mutations in 17,322 autosomal and 679 X-linked genes from exome sequences in 56,855 individuals. Estimated fitness costs for the loss of a gene copy are typically above 1%; they tend to be largest for X-linked genes, whether or not they have a Y homolog, followed by autosomal genes and genes in the pseudoautosomal region. We then compare inferred fitness effects for all possible de novo LOF mutations to those of de novo mutations identified in individuals diagnosed with one of six severe, complex diseases or developmental disorders. Probands carry an excess of mutations with estimated fitness effects above 10%; as we show by simulation, such highly deleterious mutations are typically only a couple of generations old when sampled in the population. Moreover, the proportion of highly deleterious mutations carried by probands reflects the typical age of onset of the disease. The study design also has a discernible influence: a greater proportion of highly deleterious mutations is detected in pedigree than case-control studies, and for autism, in simplex than multiplex families and in female versus male probands. Thus, anchoring observations in human genetics to a population genetic model allows us to learn about the fitness effects of mutations identified by different mapping strategies and for different traits.

genetics↗

bioRxiv2021

Mechanisms of ecological divergence with gene flow in a reef-building coral on an isolated atoll in Western Australia

Understanding the mechanisms driving phenotypic variation in traits facing intensified selection from climate change is a crucial step in developing effective conservation and restoration initiatives. This is particularly true for reef-building corals, which are among the most vulnerable to climate change and are in dramatic decline globally. At the Rowley Shoals in Western Australia, the prominent reef flat becomes exposed on low tide and the stagnant water in the shallow atoll lagoons heats up, creating a natural laboratory for characterising the mechanisms that control phenotypic responses to different environments. We combined whole genome re-sequencing, common garden heat stress experiments, transcriptome-wide gene expression analyses, and symbiont metabarcoding to explore the mechanisms that facilitate survival in contrasting habitat conditions. Our data show that, despite high gene flow between habitats, spatially varying selection drives subtle shifts in allele frequencies at hundreds of loci. These changes were concentrated into several islands of divergence spanning hundreds of SNPs that showed strong linkage disequilibrium and were associated with a coordinated increase in minor allele frequencies in corals taken from the lagoon habitat, where the range of environmental conditions is greatest. Common garden heat stress assays showed individuals from the lagoon exhibited higher bleaching resistance than colonies from the reef slope, and RNAseq identified pronounced physiological differences between the corals from the two habitats, primarily associated with molecular pathways including cell signalling, ion transport and metabolism. Despite the pronounced physioloigical and environmental differences between habitats, metabarcoding of the Symbiodiniaceae ITS2 region revealed all colonies to be associated exclusively with the genus Cladocopium, with no detectable differences between habitats. This study contributes to the growing number of studies documenting the complex mechanisms that facilitate coral survival in extreme environments, and showcases the utility of combining multiple sequencing techniques to unravel complex climate-related traits.

genomics↗

bioRxiv2020

Environmental specialization and cryptic genetic divergence in two massive coral species from the Florida Keys Reef Tract

Broadcast-spawning coral species have wide geographic ranges, spanning strong environmental gradients, but it is unclear how much spatially varying selection these gradients actually impose. Strong divergent selection might present a considerable barrier for demographic exchange between disparate reef habitats. We investigated whether the cross-shelf gradient (nearshore - offshore - deep) is associated with spatially varying selection in two common coral species, Montastraea cavernosa and Siderastrea siderea, in the Florida Keys. Toward this end, we generated a de novo genome assembly for M. cavernosa and used 2bRAD to genotype 20 juveniles and 20 adults of both species from each of the three reef zones to identify signatures of selection occurring within a single generation. Unexpectedly, each species was found to be composed of four genetically distinct lineages, with gene flow between them still ongoing but highly reduced in 13.0-54.7% of the genome. Each species includes two sympatric lineages that are only found in the deep (20 m) habitat, while the other lineages are found almost exclusively on the shallower reefs (3-10 m). The two "shallow" lineages of M. cavernosa are also specialized for either nearshore or offshore: comparison between adult and juvenile cohorts indicates that cross-shelf migrants are more than twice as likely to die before reaching adulthood than local recruits. Siderastrea siderea and M. cavernosa are among the most ecologically successful species on the degraded Florida Keys Reef Tract, and this work offers important insight on the genomic background of divergent selection and environmental specialization that may in part explain their resilience and broad environmental range.

evolutionary biology↗

bioRxiv2019

Population genetics of the coral Acropora millepora: Towards a genomic predictor of bleaching

Although reef-building corals are rapidly declining worldwide, responses to bleaching vary both within and among species. Because these inter-individual differences are partly heritable, they should in principle be predictable from genomic data. Towards that goal, we generated a chromosome-scale genome assembly for the coral Acropora millepora. We then obtained whole genome sequences for 237 phenotyped samples collected at 12 reefs distributed along the Great Barrier Reef, among which we inferred very little population structure. Scanning the genome for evidence of local adaptation, we detected signatures of long-term balancing selection in the heat-shock co-chaperone sacsin. We further used 213 of the samples to conduct a genome-wide association study of visual bleaching score, incorporating the polygenic score derived from it into a predictive model for bleaching in the wild. These results set the stage for the use of genomics-based approaches in conservation strategies.

evolutionary biology↗

bioRxiv2018

Extensive recombination suppression and chromosome-wide differentiation of a segregation distorter in Drosophila

Segregation distorters violate Mendelian Inheritance by over-representing themselves in the progeny of carrier individuals and are commonly associated with chromosomal inversions. When distorting alleles are found on sex chromosomes, the progeny of carrier individuals will exhibit skewed sex ratios, as exemplified by the array of Sex-Ratio (SR) distorting chromosomes found in Drosophila. Because of the strong selective pressures such chromosomes are thought to inflict on genomes, segregation distorters and their associated inversions are expected to experience rapid turn-over. However, the SR X-chromosome of Drosophila pseudoobscura is found at high frequencies in natural populations, forms stable latitudinal clines, appears to be unsuppressed, and shows evidence of being quite long-lived. Despite being a historically significant and well-studied segregation distortion system, the mechanisms allowing for the long-term persistence of the D. pseudoobscura SR chromosome remain unclear. Here, we perform a comparative genomic analysis between SR and uninverted standard X-chromosomes in D. pseudoobscura to study its evolutionary history and dynamics. We find a substantial level of differentiation between the SR and standard chromosome and estimate that the associated inversions have likely existed for the entire lifetime of the species (> 2 million generations). Through direct recombination experiments and population genetic analyses, we infer that this high level of differentiation is maintained by a combination of suppressed recombination and epistatic selection. Finally, our data reveal a massive mutational target size for protein and expression level changes specific to SR generated by its three non-overlapping inversions. Together our results imply that the entire SR chromosome in D. pseudoobscura behaves as a single co-adapted gene complex and has been maintained through a combination of suppressed recombination and epistatic selection. This finding highlights the dramatic consequences segregation distorters can have in shaping chromosome-wide patterns of recombination, nucleotide variation, and gene expression.

evolutionary biology↗

bioRxiv2017

Genomics of Natural Populations: Evolutionary Forces that Establish and Maintain Gene Arrangements in Drosophila pseudoosbscura

The evolution of complex traits in heterogeneous environments may shape the order of genes within chromosomes. Drosophila pseudoobscura has a rich gene arrangement polymorphism that allows one to test evolutionary genetic hypotheses about how chromosomal inversions are established in populations. D. pseudoobscura has >30 gene arrangements on a single chromosome that were generated through a series of overlapping inversion mutations with > 10 inversions with appreciable frequencies and wide geographic distributions. This study analyzes the genomic sequences of 54 strains of Drosophila pseudoobscura that carry one of six different chromosomal arrangements to test whether (1) genetic drift, (2) hitchhiking with an adaptive allele, (3) direct effects of inversions to create gene disruptions caused by breakpoints, or (4) indirect effects of inversions in limiting the formation of recombinant gametes are responsible for the establishment of new gene arrangements. We found that the inversion events do not disrupt the structure of protein coding genes at the breakpoints. Population genetic analyses of 2,669 protein coding genes identified 277 outlier loci harboring elevated frequencies of arrangement-specific derived alleles. Significant linkage disequilibrium occurs among distant loci interspersed between regions with low levels of association indicating that distant allelic combinations are held together despite shared polymorphism among arrangements. Outlier genes showing evidence of genetic differentiation between arrangements are enriched for sensory perception and detoxification genes. The data presented here support the indirect effect of inversion hypothesis where chromosomal inversions are favored because they maintain linked associations among multi-locus allelic combinations among different arrangements.

genomics↗