Biology subjects

Sackton, T. B.

Publications and source records attributed to Sackton, T. B..

7 recordsLinked to original sources

bioRxiv2018

A heterochromatic histone methyltransferase lowers nucleosome occupancy at euchromatic promoters

H3K9me3 (histone H3 modified with tri-methylation at lysine 9) is a hallmark of transcriptional silencing and heterochromatin. However, its global effects on the genome, including euchromatin, are less well understood. Here we develop Formaldehyde-Assisted Identification of Regulatory Elements (FAIRE) for C. elegans to examine the chromatin configuration of mutants that lack virtually all H3K9me3, while leaving H3K9me1 and H3K9me2 intact. We find that nucleosomes are mildly disrupted, and levels of H3K9me2 and H3K27me3 rise in mutant embryos. In addition to these expected changes, the most dramatic change occurs in euchromatin: many regions encompassing transcription start sites (TSSs) gain an average of two nucleosomes in mutants. The affected regions normally lack H3K9me3, revealing a locus non-autonomous role for H3K9me3. Affected TSSs are associated with genes that are active in epithelia and muscles, and implicated in development, locomotion, morphogenesis and transcription. Mutant embryos develop normally under ideal laboratory conditions but die when challenged, with defects in morphogenesis and development. Our findings reveal that H3K9me3 protects transcription start sites within euchromatin from nucleosome deposition. These results may be relevant to mammals, where diseases that disrupt the nuclear lamina and heterochromatin can alter epithelial and muscle gene expression.

developmental biology↗

bioRxiv2018

Immune genes are hotspots of shared positive selection across birds and mammals

Consistent patterns of positive selection in functionally similar genes can suggest a common selective pressure across a group of species. We use alignments of orthologous protein-coding genes from 39 species of birds to estimate parameters related to positive selection for 11,000 genes conserved across birds. We show that functional pathways related to the immune system, recombination, lipid metabolism, and phototransduction are enriched for positively selected genes. By comparing our results with mammalian data, we find a significant enrichment for positively selected genes shared between taxa, and that these shared selected genes are enriched for viral immune pathways. Using pathogen-challenge transcriptome data, we show that genes up-regulated in response to pathogens are also enriched for positively selected genes. Together, our results suggest that pathogens, particularly viruses, consistently target the same genes across divergent clades, and that these genes are hotspots of host-pathogen conflict over deep evolutionary time.

evolutionary biology↗

bioRxiv2018

Evolutionary dynamics of sex chromosomes of palaeognathous birds

Standard models of sex chromosome evolution propose that recombination suppression leads to the degeneration of the heterogametic chromosome, as is seen for the Y chromosome in mammals and the W chromosome in most birds. Unlike other birds, paleognaths (ratites and tinamous) possess large non-degenerate regions on their sex chromosomes (PARs or pseudoautosomal regions). It remains unclear why these large PARs are retained over more than 100 MY, and how this retention impacts the evolution of sex chromosomes within this system. To address this puzzle, we analysed Z chromosome evolution and gene expression across 12 paleognaths, several of whose genomes have recently been sequenced. We confirm at the genomic level that most paleognaths retain large PARs. As in other birds, we find that all paleognaths have incomplete dosage compensation on the regions of the Z chromosome homologous to degenerated portions of the W (differentiated regions or DRs), but we find no evidence for enrichments of male-biased genes in PARs. We find limited evidence for increased evolutionary rates (faster-Z) either across the chromosome or in DRs for most paleognaths with large PARs, but do recover signals of faster-Z evolution in tinamou species with mostly degenerated W chromosomes, similar to the pattern seen in neognaths. Unexpectedly, in some species PAR-linked genes evolve faster on average than genes on autosomes, suggested by diverse genomic features to be due to reduced efficacy of selection in paleognath PARs. Our analysis shows that paleognath Z chromosomes are atypical at the genomic level, but the evolutionary forces maintaining largely homomorphic sex chromosomes in these species remain elusive.

evolutionary biology↗

bioRxiv2018

A hierarchical Bayesian model for detecting convergent rate changes of conserved elements on phylogenetic trees

Conservation of DNA sequence over evolutionary time is a strong indicator of function, and gain or loss of sequence conservation can be used to infer changes in function across a phylogeny. Changes in evolutionary rates on particular lineages in a phylogeny can indicate shared functional shifts, and thus can be used to detect genomic correlates of phenotypic convergence. However, existing methods do not allow easy detection of patterns of rate variation, which causes challenges for detecting convergent rate shifts or other complex evolutionary scenarios. Here we introduce PhyloAcc, a new Bayesian method to model substitution rate changes in conserved elements across a phylogeny. The method assumes several categories of substitution rate for each branch on the phylogenetic tree, estimates substitution rates per category, and detects changes of substitution rate as the posterior probability of a category switch. Simulations show that PhyloAcc can detect genomic regions with rate shifts in multiple target species better than previous methods and has a higher accuracy of reconstructing complex patterns of substitution rate changes than prevalent Bayesian relaxed clock models. We demonstrate the utility of PhyloAcc in two classic examples of convergent phenotypes: loss of flight in birds and the transition to marine life in mammals. In each case, our approach reveals numerous examples of conserved non-exonic elements with accelerations specific to the phenotypically convergent lineages. Our method is widely applicable to any set of conserved elements where multiple rate changes are expected on a phylogeny.

evolutionary biology↗

bioRxiv2018

First nuclear genome assembly of an extinct moa species, the little bush moa (Anomalopteryx didiformis)

AO_SCPLOWBSTRACTC_SCPLOWHigh throughput sequencing (HTS) has revolutionized the field of ancient DNA (aDNA) by facilitating recovery of nuclear DNA for greater inference of evolutionary processes in extinct species than is possible from mitochondrial DNA alone. We used HTS to obtain ancient DNA from the little bush moa (Anomalopteryx didiformis), one of the iconic species of large, flightless birds that became extinct following human settlement of New Zealand in the 13 th century. In addition to a complete mitochondrial genome at 249.9X depth of coverage, we recover almost 900 Mb of the moa nuclear genome by mapping reads to a high quality reference genome for the emu (Dromaius novaehollandiae). This first nuclear genome assembly for moa covers approximately 75% of the 1.2 Gb emu reference with sequence contiguity sufficient to identify more than 85% of bird universal single-copy orthologs. From this assembly, we isolate 40 polymorphic microsatellites to serve as a community resource for future population-level studies in moa. We also compile data for a suite of candidate genes associated with vertebrate limb development and show that the wingless moa phenotype is likely not attributable to gene loss or pseudogenization among this candidate set. We also identify potential function-altering coding sequence variants in moa for future experimental assays.

evolutionary biology↗

bioRxiv2018

Phylogenomic analyses resolve historically contentious relationships within the Palaeognathae in the presence of an empirical anomaly zone

Palaeognathae represent one of the two basal lineages in modern birds, and comprise the volant (flighted) tinamous and the flightless ratites. Resolving palaeognath phylogenetic relationships has historically proved difficult, and short internal branches separating major palaeognath lineages in previous molecular phylogenies suggest that extensive incomplete lineage sorting (ILS) might have accompanied a rapid ancient divergence. Here, we investigate palaeognath relationships using genome-wide data sets of three types of noncoding nuclear markers, together totalling 20,850 loci and over 41 million base pairs of aligned sequence data. We recover a fully resolved topology placing rheas as the sister to kiwi and emu + cassowary that is congruent across marker types for two species tree methods (MP-EST and ASTRAL-II). This topology is corroborated by patterns of insertions for 4,274 CR1 retroelements identified from multi-species whole genome screening, and is robustly supported by phylogenomic subsampling analyses, with MP-EST demonstrating particularly consistent performance across subsampling replicates as compared to ASTRAL. In contrast, analyses of concatenated data supermatrices recover rheas as the sister to all other non-ostrich palaeognaths, an alternative that lacks retroelement support and shows inconsistent behavior under subsampling approaches. While statistically supporting the species tree topology, conflicting patterns of retroelement insertions also occur and imply high amounts of ILS across short successive internal branches, consistent with observed patterns of gene tree heterogeneity. Coalescent simulations indicate that the majority of observed topological incongruence among gene trees is consistent with coalescent variation rather than arising from gene tree estimation error alone, and estimated branch lengths for short successive internodes in the inferred species tree fall within the theoretical range encompassing the anomaly zone. Distributions of empirical gene trees confirm that the most common gene tree topology for each marker type differs from the species tree, signifying the existence of an empirical anomaly zone in palaeognaths.

evolutionary biology↗

bioRxiv2018

Convergent regulatory evolution and the origin of flightlessness in palaeognathous birds

The relative roles of regulatory and protein evolution in the origin and loss of convergent phenotypic traits is a core question in evolutionary biology. Here we combine phylogenomic, epigenomic and developmental data to show that convergent evolution of regulatory regions, but not protein-coding genes, is associated with flightlessness in palaeognathous birds, a classic example of a convergent phenotype. Eleven new genomes, including a draft genome from an extinct moa, resolve palaeognath phylogeny and show that the incidence of independent, convergent accelerations among 284,000 conserved non-exonic elements is significantly more frequent in ratites than other bird lineages. Ratite-specific acceleration of conserved regions and measures of open chromatin across eight tissues in the developing chick identify candidate regulatory regions that may have modified or lost function in ratites. Enhancer activity assays conducted in the early developing chicken forelimb confirm that volant versions of a conserved element in the first intron of the TEAD1 gene display conserved enhancer activity, whereas an accelerated flightless version fails to drive reporter gene expression. Our results show that convergent molecular changes associated with loss of flight are largely regulatory in nature.

evolutionary biology↗