RESUMO
The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5th exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin.
Assuntos
Catecol O-Metiltransferase , Galinhas , Camundongos , Animais , Galinhas/genética , Catecol O-Metiltransferase/genética , Camundongos Knockout , Melaninas/metabolismo , Pigmentação/genética , Mutação da Fase de LeituraRESUMO
Atlantic Halibut (Hippoglossus hippoglossus) has a X/Y genetic sex determination system, but the sex determining factor is not known. We produced a high-quality genome assembly from a male and identified parts of chromosome 13 as the Y chromosome due to sequence divergence between sexes and segregation of sex genotypes in pedigrees. Linkage analysis revealed that all chromosomes exhibit heterochiasmy, i.e. male-only and female-only meiotic recombination regions (MRR/FRR). We show that FRR/MRR intervals differ in nucleotide diversity and repeat class content and that this is true also for other Pleuronectidae species. We further show that remnants of a Gypsy-like transposable element insertion on chr13 promotes early male specific expression of gonadal somatic cell derived factor (gsdf). Less than 4.5 MYA, this male-determining element evolved on an autosomal FRR segment featuring pre-existing male meiotic recombination barriers, thereby creating a Y chromosome. Our findings indicate that heterochiasmy may facilitate the evolution of genetic sex determination systems relying on linkage of sexually antagonistic loci to a sex-determining factor.
Assuntos
Proteínas de Peixes/genética , Linguado/genética , Recombinação Genética , Processos de Determinação Sexual , Animais , Elementos de DNA Transponíveis , Embrião não Mamífero , Feminino , Linguado/embriologia , Expressão Gênica , Genoma , Masculino , Meiose , Regiões Promotoras Genéticas , Sequências Repetitivas de Ácido Nucleico , Cromossomos Sexuais , Cromossomo YRESUMO
The mechanisms underlying sex determination are astonishingly plastic. Particularly the triggers for the molecular machinery, which recalls either the male or female developmental program, are highly variable and have evolved independently and repeatedly. Fish show a huge variety of sex determination systems, including both genetic and environmental triggers. The advent of sex chromosomes is assumed to stabilize genetic sex determination. However, because sex chromosomes are notoriously cluttered with repetitive DNA and pseudogenes, the study of their evolution is hampered. Here we reconstruct the birth of a Y chromosome present in the Atlantic herring. The region is tiny (230 kb) and contains only three intact genes. The candidate male-determining gene BMPR1BBY encodes a truncated form of a BMP1B receptor, which originated by gene duplication and translocation and underwent rapid protein evolution. BMPR1BBY phosphorylates SMADs in the absence of ligand and thus has the potential to induce testis formation. The Y region also contains two genes encoding subunits of the sperm-specific Ca2+ channel CatSper required for male fertility. The herring Y chromosome conforms with a characteristic feature of many sex chromosomes, namely, suppressed recombination between a sex-determining factor and genes that are beneficial for the given sex. However, the herring Y differs from other sex chromosomes in that suppression of recombination is restricted to an â¼500-kb region harboring the male-specific and sex-associated regions. As a consequence, any degeneration on the herring Y chromosome is restricted to those genes located in the small region affected by suppressed recombination.
Assuntos
Peixes/genética , Cromossomos Sexuais/genética , Animais , Evolução Molecular , Feminino , Proteínas de Peixes/genética , Peixes/fisiologia , Duplicação Gênica , Masculino , ReproduçãoRESUMO
We have used the Nanopore long-read sequencing platform to demonstrate how amazingly complex the human adenovirus type 2 (Ad2) transcriptome is with a flexible splicing machinery producing a range of novel mRNAs both from the early and late transcription units. In total we report more than 900 alternatively spliced mRNAs produced from the Ad2 transcriptome whereof more than 850 are novel mRNAs. A surprising finding was that more than 50% of all E1A transcripts extended upstream of the previously defined transcriptional start site. The novel start sites mapped close to the inverted terminal repeat (ITR) and within the E1A enhancer region. We speculate that novel promoters or enhancer driven transcription, so-called eRNA transcription, is responsible for producing these novel mRNAs. Their existence was verified by a peptide in the Ad2 proteome that was unique for the E1A ITR mRNA. Although we show a high complexity of alternative splicing from most early and late regions, the E3 region was by far the most complex when expressed at late times of infection. More than 400 alternatively spliced mRNAs were observed in this region alone. These mRNAs included extended L4 mRNAs containing E3 and L5 sequences and readthrough mRNAs combining E3 and L5 sequences. Our findings demonstrate that the virus has a remarkable capacity to produce novel exon combinations, which will offer the virus an evolutionary advantage to change the gene expression repertoire and protein production in an evolving environment.IMPORTANCE Work in the adenovirus system led to the groundbreaking discovery of RNA splicing and alternative RNA splicing in 1977. These mechanisms are essential in mammalian evolution by increasing the coding capacity of a genome. Here, we have used a long-read sequencing technology to characterize the complexity of human adenovirus pre-mRNA splicing in detail. It is mindboggling that the viral genome, which only houses around 36,000 bp, not being much larger than a single cellular gene, generates more than 900 alternatively spliced mRNAs. Recently, adenoviruses have been used as the backbone in several promising SARS-CoV-2 vaccines. Further improvement of adenovirus-based vaccines demands that the virus can be tamed into an innocent carrier of foreign genes. This requires a full understanding of the components that govern adenovirus replication and gene expression.
RESUMO
We carried out whole genome resequencing of 127 chicken including red jungle fowl and multiple populations of commercial broilers and layers to perform a systematic screening of adaptive changes in modern chicken (Gallus gallus domesticus). We uncovered >21 million high quality SNPs of which 34% are newly detected variants. This panel comprises >115,000 predicted amino-acid altering substitutions as well as 1,100 SNPs predicted to be stop-gain or -loss, several of which reach high frequencies. Signatures of selection were investigated both through analyses of fixation and differentiation to reveal selective sweeps that may have had prominent roles during domestication and breed development. Contrasting wild and domestic chicken we confirmed selection at the BCO2 and TSHR loci and identified 34 putative sweeps co-localized with ALX1, KITLG, EPGR, IGF1, DLK1, JPT2, CRAMP1, and GLI3, among others. Analysis of enrichment between groups of wild vs. commercials and broilers vs. layers revealed a further panel of candidate genes including CORIN, SKIV2L2 implicated in pigmentation and LEPR, MEGF10 and SPEF2, suggestive of production-oriented selection. SNPs with marked allele frequency differences between wild and domestic chicken showed a highly significant deficiency in the proportion of amino-acid altering mutations (P<2.5×10-6). The results contribute to the understanding of major genetic changes that took place during the evolution of modern chickens and in poultry breeding.
Assuntos
Adaptação Biológica , Galinhas/genética , Genoma , Genômica , Alelos , Animais , Biologia Computacional/métodos , Frequência do Gene , Variação Genética , Genômica/métodos , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Several horse breeds have been specifically selected for the ability to exhibit alternative patterns of locomotion, or gaits. A premature stop codon in the gene DMRT3 is permissive for "gaitedness" across breeds. However, this mutation is nearly fixed in both American Standardbred trotters and pacers, which perform a diagonal and lateral gait, respectively, during harness racing. This suggests that modifying alleles must influence the preferred gait at racing speeds in these populations. A genome-wide association analysis for the ability to pace was performed in 542 Standardbred horses (n = 176 pacers, n = 366 trotters) with genotype data imputed to ~74,000 single nucleotide polymorphisms (SNPs). Nineteen SNPs on nine chromosomes (ECA1, 2, 6, 9, 17, 19, 23, 25, 31) reached genome-wide significance (p < 1.44 x 10-6). Variant discovery in regions of interest was carried out via whole-genome sequencing. A set of 303 variants from 22 chromosomes with putative modifying effects on gait was genotyped in 659 Standardbreds (n = 231 pacers, n = 428 trotters) using a high-throughput assay. Random forest classification analysis resulted in an out-of-box error rate of 0.61%. A conditional inference tree algorithm containing seven SNPs predicted status as a pacer or trotter with 99.1% accuracy and subsequently performed with 99.4% accuracy in an independently sampled population of 166 Standardbreds (n = 83 pacers, n = 83 trotters). This highly accurate algorithm could be used by owners/trainers to identify Standardbred horses with the potential to race as pacers or as trotters, according to the genotype identified, prior to initiating training and would enable fine-tuning of breeding programs with designed matings. Additional work is needed to determine both the algorithm's utility in other gaited breeds and whether any of the predictive SNPs play a physiologically functional role in the tendency to pace or tag true functional alleles.
Assuntos
Marcha/genética , Cavalos/genética , Algoritmos , Alelos , Animais , Biomarcadores , Códon sem Sentido/genética , Frequência do Gene/genética , Variação Genética/genética , Estudo de Associação Genômica Ampla , Genótipo , Locomoção/genética , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Seleção Artificial , Fatores de Transcrição/genéticaRESUMO
Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard (Podarcis muralis), which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions near genes associated with pterin [sepiapterin reductase (SPR)] and carotenoid [beta-carotene oxygenase 2 (BCO2)] metabolism, demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been coopted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles, and haplotype analysis revealed abundant transspecific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.
Assuntos
Lagartos/genética , Pigmentação da Pele/genética , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/fisiologia , Animais , Carotenoides/genética , Carotenoides/metabolismo , Cor , Dioxigenases/genética , Lagartos/metabolismo , Pigmentação/genética , Polimorfismo Genético/genética , Pterinas/metabolismoRESUMO
Genetic resistance to infectious pancreatic necrosis virus (IPNV) in Atlantic salmon is a rare example of a trait where a single locus (QTL) explains almost all of the genetic variation. Genetic marker tests based on this QTL on salmon chromosome 26 have been widely applied in selective breeding to markedly reduce the incidence of the disease. In the current study, whole genome sequencing and functional annotation approaches were applied to characterise genes and variants in the QTL region. This was complemented by an analysis of differential expression between salmon fry of homozygous resistant and homozygous susceptible genotypes challenged with IPNV. These analyses pointed to the NEDD-8 activating enzyme 1 (nae1) gene as a putative functional candidate underlying the QTL effect. The role of nae1 in IPN resistance was further assessed via CRISPR-Cas9 knockout of the nae1 gene and chemical inhibition of the nae1 protein activity in Atlantic salmon cell lines, both of which resulted in highly significant reduction in productive IPNV replication. In contrast, CRISPR-Cas9 knockout of a candidate gene previously purported to be a cellular receptor for the virus (cdh1) did not have a major impact on productive IPNV replication. These results suggest that nae1 is the causative gene underlying the major QTL affecting resistance to IPNV in salmon, provide further evidence for the critical role of neddylation in host-pathogen interactions, and highlight the value in combining high-throughput genomics approaches with targeted genome editing to understand the genetic basis of disease resistance.
Assuntos
Doenças dos Peixes , Vírus da Necrose Pancreática Infecciosa , Salmo salar , Animais , Doenças dos Peixes/genética , Marcadores Genéticos , Locos de Características Quantitativas , Salmo salar/genéticaRESUMO
Darwin's finches, inhabiting the Galápagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin's finch species and two close relatives. Phylogenetic analysis reveals important discrepancies with the phenotype-based taxonomy. We find extensive evidence for interspecific gene flow throughout the radiation. Hybridization has given rise to species of mixed ancestry. A 240 kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial development is strongly associated with beak shape diversity across Darwin's finch species as well as within the medium ground finch (Geospiza fortis), a species that has undergone rapid evolution of beak shape in response to environmental changes. The ALX1 haplotype has contributed to diversification of beak shapes among the Darwin's finches and, thereby, to an expanded utilization of food resources.
Assuntos
Bico/anatomia & histologia , Evolução Molecular , Tentilhões/anatomia & histologia , Tentilhões/genética , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Equador , Feminino , Tentilhões/classificação , Tentilhões/embriologia , Fluxo Gênico , Genoma/genética , Haplótipos/genética , Hibridização Genética , Ilhas do Oceano Índico , Masculino , Dados de Sequência Molecular , Filogenia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Although recent advances in sequencing and computational analyses have facilitated use of endogenous retroviruses (ERVs) for deciphering coevolution among retroviruses and their hosts, sampling effects from different host populations present major challenges. Here we utilize available whole-genome data from wild and domesticated European rabbit (Oryctolagus cuniculus sp.) populations, sequenced as DNA pools by paired-end Illumina technology, for identifying segregating reference as well as nonreference ERV loci, to reveal their variation along the host phylogeny and domestication history. To produce new viruses, retroviruses must insert a proviral DNA copy into the host nuclear DNA. Occasional proviral insertions into the host germline have been passed down through generations as inherited ERVs during millions of years. These ERVs represent retroviruses that were active at the time of infection and thus present a remarkable record of historical virus-host associations. To examine segregating ERVs in host populations, we apply a reference library search strategy for anchoring ERV-associated short-sequence read pairs from pooled whole-genome sequences to reference genome assembly positions. We show that most ERVs segregate along host phylogeny but also uncover radiation of some ERVs, identified as segregating loci among wild and domestic rabbits. The study targets pertinent issues regarding genome sampling when examining virus-host evolution from the genomic ERV record and offers improved scope regarding common strategies for single-nucleotide variant analyses in host population comparative genomics.
Assuntos
Animais Domésticos/virologia , Retrovirus Endógenos/genética , Genoma Viral/genética , Especificidade de Hospedeiro/genética , Animais , Hibridização Genômica Comparativa/métodos , DNA/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Filogenia , Polimorfismo de Nucleotídeo Único/genética , CoelhosRESUMO
The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.
Assuntos
Comportamento Animal/fisiologia , Domesticação , Medo/fisiologia , Substância Cinzenta , Córtex Pré-Frontal , Substância Branca , Animais , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/fisiologia , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/fisiologia , Coelhos , Substância Branca/anatomia & histologia , Substância Branca/fisiologiaRESUMO
BACKGROUND: Hypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed. RESULTS: By employing genome-wide association followed by fine-mapping (top variant p-value = 5.7 × 10- 6), integrated with whole-genome resequencing and copy number variation analysis, we detected a ~ 8.9 kbp deletion strongly associated (p-value = 0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail. CONCLUSIONS: Our results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.
Assuntos
Doenças do Cão/genética , Predisposição Genética para Doença , Doença de Hashimoto/genética , Doença de Hashimoto/veterinária , Interferon-alfa/genética , Tireoidite Autoimune/genética , Tireoidite Autoimune/veterinária , Animais , Cruzamento , Variações do Número de Cópias de DNA , Cães , Estudo de Associação Genômica Ampla , Genômica , Genótipo , Família Multigênica , Polimorfismo de Nucleotídeo Único , Deleção de SequênciaRESUMO
Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Dmrt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
Assuntos
Marcha/genética , Cavalos/genética , Cavalos/fisiologia , Mutação/genética , Medula Espinal/fisiologia , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Códon sem Sentido/genética , Marcha/fisiologia , Perfilação da Expressão Gênica , Frequência do Gene , Cavalos/classificação , Islândia , Camundongos , Dados de Sequência Molecular , Vias Neurais/fisiologia , Desempenho Psicomotor/fisiologia , Medula Espinal/citologia , Fatores de Transcrição/deficiência , Fatores de Transcrição/metabolismoRESUMO
Duplex-comb (D) is one of three major loci affecting comb morphology in the domestic chicken. Here we show that the two Duplex-comb alleles, V-shaped (D*V) and Buttercup (D*C), are both associated with a 20 Kb tandem duplication containing several conserved putative regulatory elements located 200 Kb upstream of the eomesodermin gene (EOMES). EOMES is a T-box transcription factor that is involved in mesoderm specification during gastrulation. In D*V and D*C chicken embryos we find that EOMES is ectopically expressed in the ectoderm of the comb-developing region as compared to wild-type embryos. The confinement of the ectopic expression of EOMES to the ectoderm is in stark contrast to the causal mechanisms underlying the two other major comb loci in the chicken (Rose-comb and Pea-comb) in which the transcription factors MNR2 and SOX5 are ectopically expressed strictly in the mesenchyme. Interestingly, the causal mutations of all three major comb loci in the chicken are now known to be composed of large-scale structural genomic variants that each result in ectopic expression of transcription factors. The Duplex-comb locus also illustrates the evolution of alleles in domestic animals, which means that alleles evolve by the accumulation of two or more consecutive mutations affecting the phenotype. We do not yet know whether the V-shaped or Buttercup allele correspond to the second mutation that occurred on the haplotype of the original duplication event.
Assuntos
Desenvolvimento Embrionário/genética , Gastrulação/genética , Genes Duplicados , Proteínas com Domínio T/genética , Animais , Embrião de Galinha , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Ectoderma/embriologia , Ectoderma/crescimento & desenvolvimento , Ectoderma/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Genoma , Genômica , Haplótipos , Mutação , Proteínas com Domínio T/biossínteseRESUMO
MicroRNAs (miRNAs) are important post-transcriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. The aim of this study was to investigate miRNA-mRNA interactions that may be relevant for bone metabolism by assessing correlations and interindividual variability in miRNA levels as well as global correlations between miRNA and mRNA levels in a large cohort of primary human osteoblasts (HOBs) obtained during orthopedic surgery in otherwise healthy individuals. We identified differential expression (DE) of 24 miRNAs, and found 9 miRNAs exhibiting DE between males and females. We identified hsa-miR-29b, hsa-miR-30c2, and hsa-miR-125b and their target genes as important modulators of bone metabolism. Further, we used an integrated analysis of global miRNA-mRNA correlations, mRNA-expression profiling, DE, bioinformatics analysis, and functional studies to identify novel target genes for miRNAs with the potential to regulate osteoblast differentiation and extracellular matrix production. Functional studies by overexpression and knockdown of miRNAs showed that, the differentially expressed miRNAs hsa-miR-29b, hsa-miR-30c2, and hsa-miR-125b target genes highly relevant to bone metabolism, e.g., collagen, type I, α1 (COL1A1), osteonectin (SPARC), Runt-related transcription factor 2 (RUNX2), osteocalcin (BGLAP), and frizzled-related protein (FRZB). These miRNAs orchestrate the activities of key regulators of osteoblast differentiation and extracellular matrix proteins by their convergent action on target genes and pathways to control the skeletal gene expression.
Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/citologia , Osteogênese , RNA Mensageiro/genética , Células Cultivadas , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Osteoblastos/metabolismo , RNA Mensageiro/metabolismoRESUMO
Silky-feather has been selected and fixed in some breeds due to its unique appearance. This phenotype is caused by a single recessive gene (hookless, h). Here we map the silky-feather locus to chromosome 3 by linkage analysis and subsequently fine-map it to an 18.9 kb interval using the identical by descent (IBD) method. Further analysis reveals that a C to G transversion located upstream of the prenyl (decaprenyl) diphosphate synthase, subunit 2 (PDSS2) gene is causing silky-feather. All silky-feather birds are homozygous for the G allele. The silky-feather mutation significantly decreases the expression of PDSS2 during feather development in vivo. Consistent with the regulatory effect, the C to G transversion is shown to remarkably reduce PDSS2 promoter activity in vitro. We report a new example of feather structure variation associated with a spontaneous mutation and provide new insight into the PDSS2 function.
Assuntos
Alquil e Aril Transferases/genética , Galinhas/genética , Plumas/crescimento & desenvolvimento , Sequências Reguladoras de Ácido Nucleico , Animais , Cruzamento , Plumas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Ligação Genética , Mutação , Fenótipo , Regiões Promotoras GenéticasRESUMO
The domestication of the horse â¼ 5.5 kya and the emergence of mounted riding, chariotry, and cavalry dramatically transformed human civilization. However, the genetics underlying horse domestication are difficult to reconstruct, given the near extinction of wild horses. We therefore sequenced two ancient horse genomes from Taymyr, Russia (at 7.4- and 24.3-fold coverage), both predating the earliest archeological evidence of domestication. We compared these genomes with genomes of domesticated horses and the wild Przewalski's horse and found genetic structure within Eurasia in the Late Pleistocene, with the ancient population contributing significantly to the genetic variation of domesticated breeds. We furthermore identified a conservative set of 125 potential domestication targets using four complementary scans for genes that have undergone positive selection. One group of genes is involved in muscular and limb development, articular junctions, and the cardiac system, and may represent physiological adaptations to human utilization. A second group consists of genes with cognitive functions, including social behavior, learning capabilities, fear response, and agreeableness, which may have been key for taming horses. We also found that domestication is associated with inbreeding and an excess of deleterious mutations. This genetic load is in line with the "cost of domestication" hypothesis also reported for rice, tomatoes, and dogs, and it is generally attributed to the relaxation of purifying selection resulting from the strong demographic bottlenecks accompanying domestication. Our work demonstrates the power of ancient genomes to reconstruct the complex genetic changes that transformed wild animals into their domesticated forms, and the population context in which this process took place.
Assuntos
Animais Domésticos/genética , Evolução Molecular , Genoma/fisiologia , Cavalos/genética , Animais , Sistema Cardiovascular/anatomia & histologia , Cães , Membro Posterior/anatomia & histologia , Membro Posterior/fisiologia , Cavalos/anatomia & histologia , Humanos , Endogamia , Federação RussaRESUMO
Domestic animals are excellent models for genetic studies of phenotypic evolution. They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour. Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity. Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens. We have generated 44.5-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor. We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps. One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates. Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation. We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important. This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research.
Assuntos
Galinhas/genética , Loci Gênicos/genética , Genoma/genética , Seleção Genética/genética , Sequência de Aminoácidos , Animais , Evolução Biológica , Feminino , Masculino , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Alinhamento de Sequência , Análise de Sequência de DNA , Deleção de SequênciaRESUMO
Reproductive seasonality is a trait that often differs between domestic animals and their wild ancestors, with domestic animals showing prolonged or even continuous breeding seasons. However, the genetic basis underlying this trait is still poorly understood for most species, and because environmental factors and resource availability are known to play an important role in determining breeding seasons, it is also not clear in most cases to what extent this phenotypic shift is determined by the more lenient captive conditions or by genetic factors. Here, using animals resulting from an initial cross between wild and domestic rabbits followed by two consecutive backcrosses (BC1 and BC2) to wild rabbits, we evaluated the yearly distribution of births for the different generations. Similar to domestic rabbits, F1 animals could be bred all year round but BC1 and BC2 animals showed a progressive and significant reduction in the span of the breeding season, providing experimental evidence that reduced seasonal breeding in domestic rabbits has a clear genetic component and is not a simple by-product of rearing conditions. We then took advantage of a recently published genome-wide scan of selection in the domesticated lineage and searched for candidate genes potentially associated with this phenotypic shift. Candidate genes located within regions targeted by selection include well-known examples of genes controlling clock functions (CRY1 and NR3C1) and reproduction (PRLR).
Assuntos
Coelhos/genética , Reprodução/genética , Estações do Ano , Animais , Animais Domésticos/genética , Animais Selvagens/genética , Cruzamentos Genéticos , Feminino , Masculino , FenótipoRESUMO
Domestication is one of the strongest forms of short-term, directional selection. Although selection is typically only exerted on one or a few target traits, domestication can lead to numerous changes in many seemingly unrelated phenotypes. It is unknown whether such correlated responses are due to pleiotropy or linkage between separate genetic architectures. Using three separate intercrosses between wild and domestic chickens, a locus affecting comb mass (a sexual ornament in the chicken) and several fitness traits (primarily medullary bone allocation and fecundity) was identified. This locus contains two tightly-linked genes, BMP2 and HAO1, which together produce the range of pleiotropic effects seen. This study demonstrates the importance of pleiotropy (or extremely close linkage) in domestication. The nature of this pleiotropy also provides insights into how this sexual ornament could be maintained in wild populations.