The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects ...the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health.
...we have developed a system to track individual regions that are under review. The primary assembly unit contains sequences for the non-redundant haploid assembly; this includes the scaffolds that ...make up the chromosome sequence as well as unplaced and unlocalized scaffolds that are thought to represent novel sequence (not shown in this picture).\n Additionally, we wish to engage the research and clinical communities to identify regions that require targeted effort and to incorporate information from groups performing detailed work on specific loci.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Host-parasite interactions exert strong selection pressures on the genomes of both host and parasite. These interactions can lead to negative frequency-dependent selection, a form of ...balancing selection that is hypothesised to explain the high levels of polymorphism seen in many host immune and parasite antigen loci. Here, we sequence the genomes of several individuals of
Heligmosomoides bakeri
, a model parasite of house mice, and
Heligmosomoides polygyrus
, a closely related parasite of wood mice. Although
H. bakeri
is commonly referred to as
H. polygyrus
in the literature, their genomes show levels of divergence that are consistent with at least a million years of independent evolution. The genomes of both species contain hyper-divergent haplotypes that are enriched for proteins that interact with the host immune response. Many of these haplotypes originated prior to the divergence between
H. bakeri
and
H. polygyrus
, suggesting that they have been maintained by long-term balancing selection. Together, our results suggest that the selection pressures exerted by the host immune response have played a key role in shaping patterns of genetic diversity in the genomes of parasitic nematodes.
The kākāpō is a flightless parrot endemic to New Zealand. Once common in the archipelago, only 201 individuals remain today, most of them descending from an isolated island population. We report the ...first genome-wide analyses of the species, including a high-quality genome assembly for kākāpō, one of the first chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP). We also sequenced and analyzed 35 modern genomes from the sole surviving island population and 14 genomes from the extinct mainland population. While theory suggests that such a small population is likely to have accumulated deleterious mutations through genetic drift, our analyses on the impact of the long-term small population size in kākāpō indicate that present-day island kākāpō have a reduced number of harmful mutations compared to mainland individuals. We hypothesize that this reduced mutational load is due to the island population having been subjected to a combination of genetic drift and purging of deleterious mutations, through increased inbreeding and purifying selection, since its isolation from the mainland ∼10,000 years ago. Our results provide evidence that small populations can survive even when isolated for hundreds of generations. This work provides key insights into kākāpō breeding and recovery and more generally into the application of genetic tools in conservation efforts for endangered species.
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First genome sequencing and population genomic analyses of the critically endangered kākāpōGeneration of a high-quality annotated reference genome assembly for kākāpōSequencing of 49 kākāpō genomes from surviving island and extinct mainland populationsGenomic analyses of long-term isolated populations inform conservation strategies
Dussex et al. sequence modern and historical genomes from the critically endangered kākāpō to investigate the genetic consequences of long-term small population size. They find that the remaining kākāpō from a small island population are inbred but have fewer deleterious mutations compared to the now-extinct mainland population, providing insights into conservation strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A genomic basis of vocal rhythm in birds Sebastianelli, Matteo; Lukhele, Sifiso M; Secomandi, Simona ...
Nature communications,
04/2024, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Open access
Vocal rhythm plays a fundamental role in sexual selection and species recognition in birds, but little is known of its genetic basis due to the confounding effect of vocal learning in model systems. ...Uncovering its genetic basis could facilitate identifying genes potentially important in speciation. Here we investigate the genomic underpinnings of rhythm in vocal non-learning Pogoniulus tinkerbirds using 135 individual whole genomes distributed across a southern African hybrid zone. We find rhythm speed is associated with two genes that are also known to affect human speech, Neurexin-1 and Coenzyme Q8A. Models leveraging ancestry reveal these candidate loci also impact rhythmic stability, a trait linked with motor performance which is an indicator of quality. Character displacement in rhythmic stability suggests possible reinforcement against hybridization, supported by evidence of asymmetric assortative mating in the species producing faster, more stable rhythms. Because rhythm is omnipresent in animal communication, candidate genes identified here may shape vocal rhythm across birds and other vertebrates.
Abstract
Background
The king scallop, Pecten maximus, is distributed in shallow waters along the Atlantic coast of Europe. It forms the basis of a valuable commercial fishery and plays a key role in ...coastal ecosystems and food webs. Like other filter feeding bivalves it can accumulate potent phytotoxins, to which it has evolved some immunity. The molecular origins of this immunity are of interest to evolutionary biologists, pharmaceutical companies, and fisheries management.
Findings
Here we report the genome assembly of this species, conducted as part of the Wellcome Sanger 25 Genomes Project. This genome was assembled from PacBio reads and scaffolded with 10X Chromium and Hi-C data. Its 3,983 scaffolds have an N50 of 44.8 Mb (longest scaffold 60.1 Mb), with 92% of the assembly sequence contained in 19 scaffolds, corresponding to the 19 chromosomes found in this species. The total assembly spans 918.3 Mb and is the best-scaffolded marine bivalve genome published to date, exhibiting 95.5% recovery of the metazoan BUSCO set. Gene annotation resulted in 67,741 gene models. Analysis of gene content revealed large numbers of gene duplicates, as previously seen in bivalves, with little gene loss, in comparison with the sequenced genomes of other marine bivalve species.
Conclusions
The genome assembly of P. maximus and its annotated gene set provide a high-quality platform for studies on such disparate topics as shell biomineralization, pigmentation, vision, and resistance to algal toxins. As a result of our findings we highlight the sodium channel gene Nav1, known to confer resistance to saxitoxin and tetrodotoxin, as a candidate for further studies investigating immunity to domoic acid.
Programmed DNA loss is a gene silencing mechanism that is employed by several vertebrate and nonvertebrate lineages, including all living jawless vertebrates and songbirds. Reconstructing the ...evolution of somatically eliminated (germline-specific) sequences in these species has proven challenging due to a high content of repeats and gene duplications in eliminated sequences and a corresponding lack of highly accurate and contiguous assemblies for these regions. Here, we present an improved assembly of the sea lamprey (Petromyzon marinus) genome that was generated using recently standardized methods that increase the contiguity and accuracy of vertebrate genome assemblies. This assembly resolves highly contiguous, somatically retained chromosomes and at least one germline-specific chromosome, permitting new analyses that reconstruct the timing, mode, and repercussions of recruitment of genes to the germline-specific fraction. These analyses reveal major roles of interchromosomal segmental duplication, intrachromosomal duplication, and positive selection for germline functions in the long-term evolution of germline-specific chromosomes.
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•We report an improved assembly of the sea lamprey (Petromyzon marinus) genome•The assembly resolves at least one germline-specific chromosome•Many germline-specific genes have somatic paralogs in the sea lamprey genome•Data from other species provide insight into the timing of duplication events
Timoshevskaya et al. report an improved genome assembly for sea lamprey that aids in resolving the structure and evolution of chromosomes that are programmatically eliminated during development (germline-specific chromosomes). Using data from other species, these analyses indicate major roles of duplication and selection in the long-term evolution of germline-specific chromosomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present a genome assembly from an individual female
(the malaria mosquito; Arthropoda; Insecta; Diptera; Culicidae), Ifakara strain. The genome sequence is 264 megabases in span. Most of the ...assembly is scaffolded into three chromosomal pseudomolecules with the X sex chromosome assembled. The complete mitochondrial genome was also assembled and is 15.4 kilobases in length.
We present a genome assembly from an individual male
(the malaria mosquito; Arthropoda; Insecta; Diptera; Culicidae), from a wild population in Cameroon. The genome sequence is 271 megabases in span. ...The majority of the assembly is scaffolded into three chromosomal pseudomolecules with the X sex chromosome assembled. The complete mitochondrial genome was also assembled and is 15.5 kilobases in length.
Suncus etruscus is one of the world's smallest mammals, with an average body mass of about 2 grams. The Etruscan shrew's small body is accompanied by a very high energy demand and numerous metabolic ...adaptations. Here we report a chromosome-level genome assembly using PacBio long read sequencing, 10X Genomics linked short reads, optical mapping, and Hi-C linked reads. The assembly is partially phased, with the 2.472 Gbp primary pseudohaplotype and 1.515 Gbp alternate. We manually curated the primary assembly and identified 22 chromosomes, including X and Y sex chromosomes. The NCBI genome annotation pipeline identified 39,091 genes, 19,819 of them protein-coding. We also identified segmental duplications, inferred GO term annotations, and computed orthologs of human and mouse genes. This reference-quality genome will be an important resource for research on mammalian development, metabolism, and body size control.
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