79 research outputs found
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Transfer RNA genes experience exceptionally elevated mutation rates.
Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations
The Drosophila genome nexus: a population genomic resource of 623 Drosophila melanogaster genomes, including 197 from a single ancestral range population.
Hundreds of wild-derived Drosophila melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. The most common approach to reference-based genome assembly is a single round of alignment followed by quality filtering and variant detection. We evaluated variations and extensions of this approach and settled on an assembly strategy that utilizes two alignment programs and incorporates both substitutions and short indels to construct an updated reference for a second round of mapping prior to final variant detection. Utilizing this approach, we reassembled published D. melanogaster population genomic data sets and added unpublished genomes from several sub-Saharan populations. Most notably, we present aligned data from phase 3 of the Drosophila Population Genomics Project (DPGP3), which provides 197 genomes from a single ancestral range population of D. melanogaster (from Zambia). The large sample size, high genetic diversity, and potentially simpler demographic history of the DPGP3 sample will make this a highly valuable resource for fundamental population genetic research. The complete set of assemblies described here, termed the Drosophila Genome Nexus, presently comprises 623 consistently aligned genomes and is publicly available in multiple formats with supporting documentation and bioinformatic tools. This resource will greatly facilitate population genomic analysis in this model species by reducing the methodological differences between data sets
Conserved novel ORFs in the mitochondrial genome of the ctenophore Beroe forskalii
To date, five ctenophore species’ mitochondrial genomes have been sequenced, and each contains open reading frames (ORFs) that if translated have no identifiable orthologs. ORFs with no identifiable orthologs are called unidentified reading frames (URFs). If truly protein-coding, ctenophore mitochondrial URFs represent a little understood path in early-diverging metazoan mitochondrial evolution and metabolism. We sequenced and annotated the mitochondrial genomes of three individuals of the beroid ctenophore Beroe forskalii and found that in addition to sharing the same canonical mitochondrial genes as other ctenophores, the B. forskalii mitochondrial genome contains two URFs. These URFs are conserved among the three individuals but not found in other sequenced species. We developed computational tools called pauvre and cuttlery to determine the likelihood that URFs are protein coding. There is evidence that the two URFs are under negative selection, and a novel Bayesian hypothesis test of trinucleotide frequency shows that the URFs are more similar to known coding genes than noncoding intergenic sequence. Protein structure and function prediction of all ctenophore URFs suggests that they all code for transmembrane transport proteins. These findings, along with the presence of URFs in other sequenced ctenophore mitochondrial genomes, suggest that ctenophores may have uncharacterized transmembrane proteins present in their mitochondria
Natural selection shaped the rise and fall of passenger pigeon genomic diversity.
The extinct passenger pigeon was once the most abundant bird in North America, and possibly the world. Although theory predicts that large populations will be more genetically diverse, passenger pigeon genetic diversity was surprisingly low. To investigate this disconnect, we analyzed 41 mitochondrial and 4 nuclear genomes from passenger pigeons and 2 genomes from band-tailed pigeons, which are passenger pigeons' closest living relatives. Passenger pigeons' large population size appears to have allowed for faster adaptive evolution and removal of harmful mutations, driving a huge loss in their neutral genetic diversity. These results demonstrate the effect that selection can have on a vertebrate genome and contradict results that suggested that population instability contributed to this species's surprisingly rapid extinction
Population genomics of sub-Saharan Drosophila melanogaster: African diversity and non-African admixture
(ABRIDGED) We report the genome sequencing of 139 wild-derived strains of D.
melanogaster, representing 22 population samples from the sub-Saharan ancestral
range of this species, along with one European population. Most genomes were
sequenced above 25X depth from haploid embryos. Results indicated a pervasive
influence of non-African admixture in many African populations, motivating the
development and application of a novel admixture detection method. Admixture
proportions varied among populations, with greater admixture in urban
locations. Admixture levels also varied across the genome, with localized peaks
and valleys suggestive of a non-neutral introgression process. Genomes from the
same location differed starkly in ancestry, suggesting that isolation
mechanisms may exist within African populations. After removing putatively
admixed genomic segments, the greatest genetic diversity was observed in
southern Africa (e.g. Zambia), while diversity in other populations was largely
consistent with a geographic expansion from this potentially ancestral region.
The European population showed different levels of diversity reduction on each
chromosome arm, and some African populations displayed chromosome arm-specific
diversity reductions. Inversions in the European sample were associated with
strong elevations in diversity across chromosome arms. Genomic scans were
conducted to identify loci that may represent targets of positive selection. A
disproportionate number of candidate selective sweep regions were located near
genes with varied roles in gene regulation. Outliers for Europe-Africa FST were
found to be enriched in genomic regions of locally elevated cosmopolitan
admixture, possibly reflecting a role for some of these loci in driving the
introgression of non-African alleles into African populations
Fine-Mapping Complex Inversion Breakpoints and Investigating Somatic Pairing in the Anopheles gambiae Species Complex Using Proximity-Ligation Sequencing
Phenotypic Convergence Is Not Mirrored at the Protein Level in a Lizard Adaptive Radiation.
Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster.
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