| 1. |
- Aaltonen, Kristina, et al.
(författare)
-
Molecular Population Genetics of the SRK and SCR Self-incompatibility Genes in the Wild Plant Species Brassica cretica (Brassicaceae).
- 2009
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 181:3, s. 985-995
-
Tidskriftsartikel (refereegranskat)abstract
- Self-incompatibility (SI) in plants is a classic example of a trait evolving under strong frequency-dependent selection. As a consequence, population genetic theory predicts that the S locus, which controls SI, should maintain numerous alleles, display a high level of nucleotide diversity, and, in structured populations, show a lower level of among-population differentiation compared to neutral loci. Population-level investigations of DNA sequence variation at the S locus have recently been carried out in the genus Arabidopsis, largely confirming results from theoretical models of S-locus evolutionary dynamics, but no comparable studies have been done in wild Brassica species. In this study, we sequenced parts of the S-locus genes SRK and SCR, two tightly linked genes that are directly involved in the determination of SI specificity, in samples from four natural populations of the wild species Brassica cretica. The amount and distribution of nucleotide diversity, as well as the frequency spectrum of putative functional haplotypes, observed at the S locus in B. cretica fit very well with expectations from theoretical models, providing strong evidence for frequency-dependent selection acting on the S locus in a wild Brassica species.
|
|
| 2. |
- Aaltonen, Kristina, et al.
(författare)
-
The Evolution and Diversification of S-locus Haplotypes in the Brassicaceae Family.
- 2009
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 181:3, s. 977-984
-
Tidskriftsartikel (refereegranskat)abstract
- Self-incompatibility (SI) in the Brassicaceae plant family is controlled by the SRK and SCR genes situated at the S locus. A large number of S haplotypes have been identified, mainly in cultivated species of the Brassica and Raphanus genera, but recently also in wild Arabidopsis species. Here, we used DNA sequences from the SRK and SCR genes of the wild Brassica species B. cretica, together with publicly available sequence data from other Brassicaceae species, to investigate the evolutionary relationships between S haplotypes in the Brassicaceae family. The results reveal that wild and cultivated Brassica species have similar levels of SRK diversity indicating that domestication has had but a minor effect on S-locus diversity in Brassica. Our results also show that a common set of S haplotypes were present in the ancestor of the Brassica and Arabidopsis genera, that only a small number of haplotypes survived in the Brassica lineage after its separation from Arabidopsis, and that diversification within the two Brassica dominance classes occurred after the split between the two lineages. We also find indications that recombination may have occurred between the kinase domain of SRK and the SCR gene in Brassica.
|
|
| 3. |
- Albert, Frank W., et al.
(författare)
-
Genetic architecture of tameness in a rat model of animal domestication
- 2009
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 182:2, s. 541-554
-
Tidskriftsartikel (refereegranskat)abstract
- A common feature of domestic animals is tameness - i.e., they tolerate and are unafraid of human presence and handling. To gain insight into the genetic basis of tameness and aggression, we studied an intercross between two lines of rats (Rattus norvegicus) selected over >60 generations for increased tameness and increased aggression against humans, respectively. We measured 45 traits, including tameness and aggression, anxiety-related traits, organ weights, and levels of serum components in >700 rats from an intercross population. Using 201 genetic markers, we identified two significant quantitative trait loci (QTL) for tameness. These loci overlap with QTL for adrenal gland weight and for anxiety-related traits and are part of a five-locus epistatic network influencing tameness. An additional QTL influences the occurrence of white coat spots, but shows no significant effect on tameness. The loci described here are important starting points for finding the genes that cause tameness in these rats and potentially in domestic animals in general.
|
|
| 4. |
- Álvarez-Castro, José M., et al.
(författare)
-
A unified model for functional and statistical epistasis and its application in quantitative trait loci analysis
- 2007
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 176:2, s. 1151-1167
-
Tidskriftsartikel (refereegranskat)abstract
- Interaction between genes, or epistasis, is found to be common and it is a key, concept for understanding adaptation and evolution of natural populations, response to selection in breeding programs, and determination of complex disease. Current]),, two independent classes of models are used to study epistasis. Statistical models focus on maintaining desired statistical properties for detection and estimation of genetic effects and for the decomposition of genetic variance using average effects of allele Substitutions in populations as parameters. Functional models focus on the evolutionary consequences of the attributes of the genotype-phenotype map using natural effects of allele substitutions as parameters. Here we provide a new, general and unified model framework: the natural and orthogonal interactions (NOIA) model. NOIA implements tools for transforming genetic effects measured in One Population to the ones of other populations (e.g., between two experimental designs for QTL) and parameters of statistical and functional epistasis into each other (thus enabling us to obtain functional estimates of QTL), as demonstrated numerically. We develop graphical interpretations of functional and statistical models as regressions of the genotypic values on the gene content, which illustrates the difference between the models-the constraint on the slope of the functional regression-and when the models are equivalent. Furthermore, we use our theoretical foundations to conceptually clarify functional and statistical epistasis, discuss the advantages of NOIA over previous theory, and stress the importance of linking functional and statistical models.
|
|
| 5. |
- Athanasiadis, G, et al.
(författare)
-
Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity
- 2016
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 1943-2631. ; 204:2, s. 711-
-
Tidskriftsartikel (refereegranskat)abstract
- Denmark has played a substantial role in the history of Northern Europe. Through a nationwide scientific outreach initiative, we collected genetic and anthropometrical data from ∼800 high school students and used them to elucidate the genetic makeup of the Danish population, as well as to assess polygenic predictions of phenotypic traits in adolescents. We observed remarkable homogeneity across different geographic regions, although we could still detect weak signals of genetic structure reflecting the history of the country. Denmark presented genomic affinity with primarily neighboring countries with overall resemblance of decreasing weight from Britain, Sweden, Norway, Germany, and France. A Polish admixture signal was detected in Zealand and Funen, and our date estimates coincided with historical evidence of Wend settlements in the south of Denmark. We also observed considerably diverse demographic histories among Scandinavian countries, with Denmark having the smallest current effective population size compared to Norway and Sweden. Finally, we found that polygenic prediction of self-reported adolescent height in the population was remarkably accurate (R2 = 0.639 ± 0.015). The high homogeneity of the Danish population could render population structure a lesser concern for the upcoming large-scale gene-mapping studies in the country.
|
|
| 6. |
- Backström, Niclas, et al.
(författare)
-
A Gene-Based Genetic Linkage Map of the Collared Flycatcher (Ficedula albicollis) Reveals Extensive Synteny and Gene-Order Conservation During 100 Million Years of Avian Evolution
- 2008
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 179, s. 1479-1495
-
Tidskriftsartikel (refereegranskat)abstract
- By taking advantage of a recently developed reference markerset for avian genome analysis we have constructed a gene-basedgenetic map of the collared flycatcher, an important "ecologicalmodel" for studies of life-history evolution, sexual selection,speciation, and quantitative genetics. A pedigree of 322 birdsfrom a natural population was genotyped for 384 single nucleotidepolymorphisms (SNPs) from 170 protein-coding genes and 71 microsatellites.Altogether, 147 gene markers and 64 microsatellites form 33linkage groups with a total genetic distance of 1787 cM. Malerecombination rates are, on average, 22% higher than femalerates (total distance 1982 vs. 1627 cM). The ability to anchorthe collared flycatcher map with the chicken genome via thegene-based SNPs revealed an extraordinary degree of both syntenyand gene-order conservation during avian evolution. The greatmajority of chicken chromosomes correspond to a single linkagegroup in collared flycatchers, with only a few cases of inter-and intrachromosomal rearrangements. The rate of chromosomaldiversification, fissions/fusions, and inversions combined isthus considerably lower in birds (0.05/MY) than in mammals (0.6–2.0/MY).A dearth of repeat elements, known to promote chromosomal breakage,in avian genomes may contribute to their stability. The degreeof genome stability is likely to have important consequencesfor general evolutionary patterns and may explain, for example,the comparatively slow rate by which genetic incompatibilityamong lineages of birds evolves.
|
|
| 7. |
- Backström, Niclas, et al.
(författare)
-
Genetic mapping in a natural population of collared flycatchers (Ficedula albicollis) : Conserved synteny but gene order rearrangements on the avian Z chromosome
- 2006
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 174:1, s. 377-386
-
Tidskriftsartikel (refereegranskat)abstract
- Data from completely sequenced genomes are likely to open the way for novel studies of the genetics of nonmodel organisms, in particular when it comes to the identification and analysis of genes responsible for traits that are under selection in natural populations. Here we use the draft sequence of the chicken genome as a starting point for linkage mapping in a wild bird species, the collared flycatcher-one of the most well-studied avian species in ecological and evolutionary research. A pedigree of 365 flycatchers was established and genotyped for single nucleotide polymorphisms in 23 genes selected from (and spread over most of) the chicken Z chromosome. All genes were also found to be located on the Z chromosome in the collared flycatcher, confirming conserved synteny at the level of gene content across distantly related avian lineages. This high degree of conservation mimics the situation seen for the mammalian X chromosome and may thus be a general feature in sex chromosome evolution, irrespective of whether there is male or female heterogamety. Alternatively, such unprecedented chromosomal conservation may be characteristic of most chromosomes in avian genome evolution. However, several internal rearrangements were observed, meaning that the transfer of map information from chicken to nonmodel bird species cannot always assume conserved gene orders. Interestingly, the rate of recombination on the Z chromosome of collared flycatchers was only similar to 50% that of chicken, challenging the widely held view that birds generally have high recombination rates.
|
|
| 8. |
- Barsoum, Emad, 1979-, et al.
(författare)
-
Ume6 is required for the MATa/MATα cellular identity and transcriptional silencing in Kluyveromyces lactis
- 2010
-
Ingår i: Genetics. - : The Genetics Society of America. - 0016-6731 .- 1943-2631. ; 184:4, s. 999-1011
-
Tidskriftsartikel (refereegranskat)abstract
- To explore the similarities and differences of regulatory circuits among budding yeasts, we characterized the role of the unscheduled meiotic gene expression 6 (UME6) gene in Kluyveromyces lactis. We found that Ume6 was required for transcriptional silencing of the cryptic mating-type loci HMLα and HMRa. Chromatin immunoprecipitation (ChIP) suggested that Ume6 acted directly by binding the cis-regulatory silencers of these loci. Unexpectedly, a MATa ume6 strain was mating proficient, whereas a MATα ume6 strain was sterile. This observation was explained by the fact that ume6 derepressed HMLα2 only weakly, but derepressed HMRa1 strongly. Consistently, two a/α-repressed genes (MTS1 and STE4) were repressed in the MATα ume6 strain, but were expressed in the MATa ume6 strain. Surprisingly, ume6 partially suppressed the mating defect of a MATa sir2 strain. MTS1 and STE4 were repressed in the MATa sir2 ume6 double-mutant strain, indicating that the suppression acted downstream of the a1/α2-repressor. We show that both STE12 and the MATa2/HMRa2 genes were overexpressed in the MATa sir2 ume6 strain. Consistent with the idea that this deregulation suppressed the mating defect, ectopic overexpression of Ste12 and a2 in a MATa sir2 strain resulted in efficient mating. In addition, Ume6 served as a block to polyploidy, since ume6/ume6 diploids mated as pseudo a-strains. Finally, Ume6 was required for repression of three meiotic genes, independently of the Rpd3 and Sin3 corepressors.
|
|
| 9. |
- Baumdicker, F, et al.
(författare)
-
Efficient ancestry and mutation simulation with msprime 1.0
- 2022
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 1943-2631. ; 220:3
-
Tidskriftsartikel (refereegranskat)abstract
- Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.
|
|
| 10. |
- Bengtsson, Bengt Olle
(författare)
-
Asexuals, Polyploids, Evolutionary Opportunists ...: The Population Genetics of Positive but Deteriorating Mutations.
- 2012
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 191:4, s. 499-1393
-
Tidskriftsartikel (refereegranskat)abstract
- Some genetic phenomena originate as mutations that are initially advantageous but decline in fitness until they become distinctly deleterious. Here I give the condition for a mutation-selection balance to form and describe some of the properties of the resulting equilibrium population. A characterization is also given of the fixation probabilities for such mutations.
|
|
| 11. |
- Bengtsson, Bengt Olle, et al.
(författare)
-
The 1948 international congress of genetics in Sweden: People and politics.
- 2010
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 185:3, s. 709-715
-
Tidskriftsartikel (refereegranskat)abstract
- The International Congresses have played an important role in the history of genetics. The Eighth International Congress, which in 1948 was held in Sweden, celebrated the conclusion of the war against Nazism and many new decisive scientific advances. It also signaled a hardening of the fight against Lysenkoism, which was growing in strength in the Soviet Union. A rare document is available from the Congress-an amateur film made by a young delegate, Nils Nybom. With its help a living description can be given of the scientific and political melees in which the delegates were involved.
|
|
| 12. |
- Berger, David, et al.
(författare)
-
Biased Estimates of Diminishing-Returns Epistasis? : Empirical Evidence Revisited
- 2014
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 198:4, s. 1417-1420
-
Tidskriftsartikel (refereegranskat)abstract
- Empirical evidence for diminishing fitness returns of beneficial mutations supports Fisher's geometric model. We show that a similar pattern emerges through the phenomenon of regression to the mean and that few studies correct for it. Although biases are often small, regression to the mean has overemphasized diminishing returns and will hamper cross-study comparisons unless corrected for.
|
|
| 13. |
- Bhuiyan, Hasanuzzaman, et al.
(författare)
-
Meiotic chromosome synapsis in yeast can occur without spo11 induced DNA double strand breaks
- 2004
-
Ingår i: Genetics. - : Genetics. - 0016-6731 .- 1943-2631. ; 168:2, s. 775-783
-
Tidskriftsartikel (refereegranskat)abstract
- Proper chromosome segregation and formation of viable gametes depend on synapsis and recombination between homologous chromosomes during meiosis. Previous reports have shown that the synaptic structures, the synaptonemal complexes (SCs), do not occur in yeast cells with the SPO11 gene removed. The Spo11 enzyme makes double-strand breaks (DSBs) in the DNA and thereby initiates recombination. The view has thus developed that synapsis in yeast strictly depends on the initiation of recombination. Synapsis in some other species (Drosophila melanogaster and Caenorhabditis elegans) is independent of recombination events, and SCs are found in spo11 mutants. This difference between species led us to reexamine spo11 deletion mutants of yeast. Using antibodies against Zip1, a SC component, we found that a small fraction (1%) of the spo11 null mutant cells can indeed form wild-type-like SCs. We further looked for synapsis in a spo11 mutant strain that accumulates pachytene cells (spo11Delta ndt80Delta), and found that the frequency of cells with apparently complete SC formation was 10%. Other phenotypic criteria, such as spore viability and homologous chromosome juxtaposition measured by FISH labeling of chromosomal markers, agree with several previous reports of the spo11 mutant. Our results demonstrate that although the Spo11-induced DSBs obviously promote synapsis in yeast, the presence of Spo11 is not an absolute requirement for synapsis.
|
|
| 14. |
- Bivik, Caroline, et al.
(författare)
-
Novel Genes Involved in Controlling Specification of Drosophila FMRFamide Neuropeptide Cells
- 2015
-
Ingår i: Genetics. - : Genetics Society of America. - 0016-6731 .- 1943-2631. ; 200:4, s. 1229-1244
-
Tidskriftsartikel (refereegranskat)abstract
- The expression of neuropeptides is often extremely restricted in the nervous system, making them powerful markers for addressing cell specification . In the developing Drosophila ventral nerve cord, only six cells, the Ap4 neurons, of some 10,000 neurons, express the neuropeptide FMRFamide (FMRFa). Each Ap4/FMRFa neuron is the last-born cell generated by an identifiable and well-studied progenitor cell, neuroblast 5-6 (NB5-6T). The restricted expression of FMRFa and the wealth of information regarding its gene regulation and Ap4 neuron specification makes FMRFa a valuable readout for addressing many aspects of neural development, i.e., spatial and temporal patterning cues, cell cycle control, cell specification, axon transport, and retrograde signaling. To this end, we have conducted a forward genetic screen utilizing an Ap4-specific FMRFa-eGFP transgenic reporter as our readout. A total of 9781 EMS-mutated chromosomes were screened for perturbations in FMRFa-eGFP expression, and 611 mutants were identified. Seventy-nine of the strongest mutants were mapped down to the affected gene by deficiency mapping or whole-genome sequencing. We isolated novel alleles for previously known FMRFa regulators, confirming the validity of the screen. In addition, we identified novel essential genes, including several with previously undefined functions in neural development. Our identification of genes affecting most major steps required for successful terminal differentiation of Ap4 neurons provides a comprehensive view of the genetic flow controlling the generation of highly unique neuronal cell types in the developing nervous system.
|
|
| 15. |
- Bodhicharla, Rakesh, et al.
(författare)
-
Membrane Fluidity Is Regulated Cell Nonautonomously by Caenorhabditis elegans PAQR-2 and Its Mammalian Homolog AdipoR2
- 2018
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 210:1, s. 189-201
-
Tidskriftsartikel (refereegranskat)abstract
- Maintenance of membrane properties is an essential aspect of cellular homeostasis of which the regulatory mechanisms remain mostly uncharacterized. In Caenorhabditis elegans, the PAQR-2 and IGLR-2 proteins act together as a plasma membrane sensor that responds to decreased fluidity by promoting fatty acid desaturation, hence restoring membrane fluidity. Here, we used mosaic analysis for paqr-2 and iglr-2, and tissue-specific paqr-2 expression, to show that membrane homeostasis is achieved cell nonautonomously. Specifically, we found that expression of paqr-2 in the hypodermis, gonad sheath cells, or intestine is sufficient to suppress systemic paqr-2 mutant phenotypes, including tail tip morphology, membrane fluidity in intestinal cells, cold and glucose intolerance, vitellogenin transport to the germline, germ cell development, and brood size. Finally, we show that the cell nonautonomous regulation of membrane homeostasis is conserved in human cells: HEK293 cells that express AdipoR2, a homolog of paqr-2, are able to normalize membrane fluidity in distant cells where AdipoR2 has been silenced. Finally, using C. elegans mutants and small interfering RNA against Δ9 stearoyl-CoA desaturase in HEK293 cells, we show that Δ9 desaturases are essential for the cell nonautonomous maintenance of membrane fluidity. We conclude that cells are able to share membrane components even when they are not in direct contact with each other, and that this contributes to the maintenance of membrane homeostasis in C. elegans and human cells.
|
|
| 16. |
- Borge, Thomas, et al.
(författare)
-
Contrasting patterns of polymorphism and divergence on the Z chromosome and autosomes in two Ficedula flycatcher species
- 2005
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 171:4, s. 1861-1873
-
Tidskriftsartikel (refereegranskat)abstract
- In geographic areas where pied and collared flycatchers (Ficedula hypoleuca and F. albicollis) breed in sympatry, hybridization occurs, leading to gene flow (introgression) between the two recently diverged species. Notably, while such introgression is observable at autosomal loci it is apparently absent at the Z chromosome, suggesting an important role for genes on the Z chromosome in creating reproductive isolation during speciation. To further understand the role of Z-linked loci in the formation of new species, we studied genetic variation of the two species from regions where they live in allopatry. We analyzed patterns of polymorphism and divergence in introns from 9 Z-linked and 23 autosomal genes in pied and collared flycatcher males. Average variation on the Z chromosome is greatly reduced compared to neutral expectations based on autosomal diversity in both species. We also observe significant heterogeneity between patterns of polymorphism and divergence at Z-linked loci and a relative absence of polymorphisms that are shared by the two species on the Z chromosome compared to the autosomes. We suggest that these observations may indicate the action of recurrent selective sweeps on the Z chromosome during the evolution of the two species, which may be caused by sexual selection acting on Z-linked genes. Alternatively, reduced variation on the Z chromosome could result from substantially higher levels of introgression at autosomal than at Z-linked loci or from a complex demographic history, such as a population bottleneck.
|
|
| 17. |
- Brandström, Mikael, et al.
(författare)
-
The genomic landscape of short insertion and deletion polymorphisms in the chicken (Gallus gallus) genome : A high frequency of deletions in tandem duplicates
- 2007
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 176:3, s. 1691-1701
-
Tidskriftsartikel (refereegranskat)abstract
- It is increasingly recognized that insertions and deletions(indels) are an important source of genetic as well as phenotypicdivergence and diversity. We analyzed length polymorphisms identifiedthrough partial (0.25x) shotgun sequencing of three breeds ofdomestic chicken made by the International Chicken PolymorphismMap Consortium. A data set of 140,484 short indel polymorphismsin unique DNA was identified after filtering for microsatellitestructures. There was a significant excess of tandem duplicatesat indel sites, with deletions of a duplicate motif outnumberingthe generation of duplicates through insertion. Indel densitywas lower in microchromosomes than in macrochromosomes, in theZ chromosome than in autosomes, and in 100 bp of upstream sequence,5'-UTR, and first introns than in intergenic DNA and in otherintrons. Indel density was highly correlated with single nucleotidepolymorphism (SNP) density. The mean density of indels in pairwisesequence comparisons was 1.9 x 10–4 indel events/bp, 5%the density of SNPs segregating in the chicken genome. The greatmajority of indels involved a limited number of nucleotides(median 1 bp), with A-rich motifs being overrepresented at indelsites. The overrepresentation of deletions at tandem duplicatesindicates that replication slippage in duplicate sequences isa common mechanism behind indel mutation. The correlation betweenindel and SNP density indicates common effects of mutation and/orselection on the occurrence of indels and point mutations.
|
|
| 18. |
- Carlborg, Örjan, et al.
(författare)
-
The use of a genetic algorithm for simultaneous mapping of multiple interacting quantitative trait loci.
- 2000
-
Ingår i: Genetics. - 0016-6731 .- 1943-2631. ; 155:4
-
Tidskriftsartikel (refereegranskat)abstract
- Here we describe a general method for improving computational efficiency in simultaneous mapping of multiple interacting quantitative trait loci (QTL). The method uses a genetic algorithm to search for QTL in the genome instead of an exhaustive enumerative ("step-by-step") search. It can be used together with any method of QTL mapping based on a genomic search, since it only provides a more efficient way to search the genome for QTL. The computational demand decreases by a factor of approximately 130 when using genetic algorithm-based mapping instead of an exhaustive enumerative search for two QTL in a genome size of 2000 cM using a resolution of 1 cM. The advantage of using a genetic algorithm increases further for larger genomes, higher resolutions, and searches for more QTL. We show that a genetic algorithm-based search has efficiency higher than or equal to a search method conditioned on previously identified QTL for all epistatic models tested and that this efficiency is comparable to that of an exhaustive search for multiple QTL. The genetic algorithm is thus a powerful and computationally tractable alternative to the exhaustive enumerative search for simultaneous mapping of multiple interacting QTL. The use of genetic algorithms for simultaneous mapping of more than two QTL and for determining empirical significance thresholds using permutation tests is also discussed.
|
|
| 19. |
- Carneiro, Miguel, et al.
(författare)
-
Dwarfism and Altered Craniofacial Development in Rabbits Is Caused by a 12.1 kb Deletion at the HMGA2 Locus
- 2017
-
Ingår i: Genetics. - : GENETICS SOCIETY AMERICA. - 0016-6731 .- 1943-2631. ; 205:2, s. 955-965
-
Tidskriftsartikel (refereegranskat)abstract
- The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds. Here, we show that the dwarf allele constitutes a similar to 12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene. HMGA2 has been frequently associated with variation in body size across species. Homozygotes for null alleles are viable in mice but not in rabbits and probably not in humans. RNA-sequencing analysis of rabbit embryos showed that very few genes (4-29 genes) were differentially expressed among the three HMGA2/dwarf genotypes, suggesting that dwarfism and inviability in rabbits are caused by modest changes in gene expression. Our results show that HMGA2 is critical for normal expression of IGF2BP2, which encodes an RNA-binding protein. Finally, we report a catalog of regions of elevated genetic differentiation between dwarf and normal-size rabbits, including LCORL-NCAPG, STC2, HOXD cluster, and IGF2BP2. Levels and patterns of genetic diversity at the LCORL-NCAPG locus further suggest that small size in dwarf breeds was enhanced by crosses with wild rabbits. Overall, our results imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection.
|
|
| 20. |
- Catalan, Ana, et al.
(författare)
-
Drift and Directional Selection Are the Evolutionary Forces Driving Gene Expression Divergence in Eye and Brain Tissue of Heliconius Butterflies
- 2019
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 213:2, s. 581-594
-
Tidskriftsartikel (refereegranskat)abstract
- Investigating gene expression evolution over micro- and macroevolutionary timescales will expand our understanding of the role of gene expression in adaptation and speciation. In this study, we characterized the evolutionary forces acting on gene expression levels in eye and brain tissue of five Heliconius butterflies with divergence times of similar to 5-12 MYA. We developed and applied Brownian motion (BM) and Ornstein-Uhlenbeck (OU) models to identify genes whose expression levels are evolving through drift, stabilizing selection, or a lineage-specific shift. We found that 81% of the genes evolve under genetic drift. When testing for branch-specific shifts in gene expression, we detected 368 (16%) shift events. Genes showing a shift toward upregulation have significantly lower gene expression variance than those genes showing a shift leading toward downregulation. We hypothesize that directional selection is acting in shifts causing upregulation, since transcription is costly. We further uncovered through simulations that parameter estimation of OU models is biased when using small phylogenies and only becomes reliable with phylogenies having >= 50 taxa. Therefore, we developed a new statistical test based on BM to identify highly conserved genes (i.e., evolving under strong stabilizing selection), which comprised 3% of the orthoclusters. In conclusion, we found that drift is the dominant evolutionary force driving gene expression evolution in eye and brain tissue in Heliconius. Nevertheless, the higher proportion of genes evolving under directional than under stabilizing selection might reflect species-specific selective pressures on vision and the brain that are necessary to fulfill species-specific requirements. Characterization of gene expression patterns across species - and the evolutionary forces driving them - can reveal processes that have remained conserved across species, as well as those that have changed in a species- specific manner...
|
|
| 21. |
- Charlesworth, Deborah, et al.
(författare)
-
Trans-specificity at Loci Near the Self-Incompatibility Loci in Arabidopsis
- 2006
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 172:4, s. 2699-2704
-
Tidskriftsartikel (refereegranskat)abstract
- We compared allele sequences of two loci near the Arabidopsis lyrata self-incompatibility (S) loci with sequences of A. thaliana orthologs and found high numbers of shared polymorphisms, even excluding singletons and sites likely to be highly mutable. This suggests maintenance of entire S-haplotypes for long evolutionary times and extreme recombination suppression in the region.
|
|
| 22. |
- Chen, Jun, et al.
(författare)
-
Clinal Variation at Phenology-Related Genes in Spruce : Parallel Evolution in FTL2 and Gigantea?
- 2014
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 197:3, s. 1025-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Parallel clines in different species, or in different geographical regions of the same species, are an important source of information on the genetic basis of local adaptation. We recently detected latitudinal clines in SNPs frequencies and gene expression of candidate genes for growth cessation in Scandinavian populations of Norway spruce (Picea abies). Here we test whether the same clines are also present in Siberian spruce (P. obovata), a close relative of Norway spruce with a different Quaternary history. We sequenced nine candidate genes and 27 control loci and genotyped 14 SSR loci in six populations of P. obovata located along the Yenisei river from latitude 56 N to latitude 67 N. In contrast to Scandinavian Norway spruce that both departs from the standard neutral model (SNM) and shows a clear population structure, Siberian spruce populations along the Yenisei do not depart from the SNM and are genetically unstructured. Nonetheless, as in Norway spruce, growth cessation is significantly clinal. Polymorphisms in photoperiodic (FTL2) and circadian clock (Gigantea, GI, PRR3) genes also show significant clinal variation and/or evidence of local selection. In GI, one of the variants is the same as in Norway spruce. Finally, a strong cline in gene expression is observed for FTL2, but not for GI. These results, together with recent physiological studies, confirm the key role played by FTL2 and circadian clock genes in the control of growth cessation in spruce species and suggest the presence of parallel adaptation in these two species.
|
|
| 23. |
- Chen, Jun, et al.
(författare)
-
Disentangling the Roles of History and Local Selection in Shaping Clinal Variation of Allele Frequencies and Gene Expression in Norway Spruce (Picea abies)
- 2012
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 191:3, s. 865-881
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the genetic basis of local adaptation is challenging due to the subtle balance among conflicting evolutionary forces that are involved in its establishment and maintenance. One system with which to tease apart these difficulties is clines in adaptive characters. Here we analyzed genetic and phenotypic variation in bud set, a highly heritable and adaptive trait, among 18 populations of Norway spruce (Picea abies), arrayed along a latitudinal gradient ranging from 47°N to 68°N. We confirmed that variation in bud set is strongly clinal, using a subset of five populations. Genotypes for 137 single-nucleotide polymorphisms (SNPs) chosen from 18 candidate genes putatively affecting bud set and 308 control SNPs chosen from 264 random genes were analyzed for patterns of genetic structure and correlation to environment. Population genetic structure was low (F(ST) = 0.05), but latitudinal patterns were apparent among Scandinavian populations. Hence, part of the observed clinal variation should be attributable to population demography. Conditional on patterns of genetic structure, there was enrichment of SNPs within candidate genes for correlations with latitude. Twenty-nine SNPs were also outliers with respect to F(ST). The enrichment for clinal variation at SNPs within candidate genes (i.e., SNPs in PaGI, PaPhyP, PaPhyN, PaPRR7, and PaFTL2) indicated that local selection in the 18 populations, and/or selection in the ancestral populations from which they were recently derived, shaped the observed cline. Validation of these genes using expression studies also revealed that PaFTL2 expression is significantly associated with latitude, thereby confirming the central role played by this gene in the control of phenology in plants.
|
|
| 24. |
- Chen, Jun, et al.
(författare)
-
From Drift to Draft : How Much Do Beneficial Mutations Actually Contribute to Predictions of Ohta's Slightly Deleterious Model of Molecular Evolution?
- 2020
-
Ingår i: Genetics. - : GENETICS SOCIETY AMERICA. - 0016-6731 .- 1943-2631. ; 214:4, s. 1005-1018
-
Tidskriftsartikel (refereegranskat)abstract
- Since its inception in 1973, the slightly deleterious model of molecular evolution, also known as the nearly neutral theory of molecular evolution, remains a central model to explain the main patterns of DNA polymorphism in natural populations. This is not to say that the quantitative fit to data are perfect. A recent study used polymorphism data from Drosophila melanogaster to test whether, as predicted by the nearly neutral theory, the proportion of effectively neutral mutations depends on the effective population size (N-e). It showed that a nearly neutral model simply scaling with N-e variation across the genome could not alone explain the data, but that consideration of linked positive selection improves the fit between observations and predictions. In the present article, we extended the work in two main directions. First, we confirmed the observed pattern on a set of 59 species, including high-quality genomic data from 11 animal and plant species with different mating systems and effective population sizes, hence a priori different levels of linked selection. Second, for the 11 species with high-quality genomic data we also estimated the full distribution of fitness effects (DFE) of mutations, and not solely the DFE of deleterious mutations. Both N-e and beneficial mutations contributed to the relationship between the proportion of effectively neutral mutations and local N-e across the genome. In conclusion, the predictions of the slightly deleterious model of molecular evolution hold well for species with small N-e, but for species with large N-e, the fit is improved by incorporating linked positive selection to the model.
|
|
| 25. |
- Chien, Jason, et al.
(författare)
-
Regulation of Axon Guidance by the Wnt Receptor Ror/CAM-1 in the PVT Guidepost Cell in Caenorhabditis elegans
- 2017
-
Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 207:4, s. 1533-1545
-
Tidskriftsartikel (refereegranskat)abstract
- The Caenorhabditis elegans ventral nerve cord (VNC) consists of two asymmetric bundles of neurons and axons that are separated by the midline. How the axons are guided to stay on the correct sides of the midline remains poorly understood. Here we provide evidence that the conserved Wnt signaling pathway along with the Netrin and Robo pathways constitute a combinatorial code for midline guidance of PVP and PVQ axons that extend into the VNC. Combined loss of the Wnts CWN-1, CWN-2, and EGL-20 or loss of the Wnt receptor CAM-1 caused. >70% of PVP and PVQ axons to inappropriately cross over from the left side to the right side. Loss of the Frizzled receptor LIN-17 or the planar cell polarity (PCP) protein VANG-1 also caused cross over defects that did not enhance those in the cam-1 mutant, indicating that the proteins function together in midline guidance. Strong cam-1 expression can be detected in the PVQs and the guidepost cell PVT that is located on the midline. However, only when cam-1 is expressed in PVT are the crossover defects of PVP and PVQ rescued, showing that CAM-1 functions nonautonomously in PVT to prevent axons from crossing the midline.
|
|
