RESUMEN
Variation in the size and number of axial segments underlies much of the diversity in animal body plans. Here we investigate the evolutionary, genetic and developmental mechanisms driving tail-length differences between forest and prairie ecotypes of deer mice (Peromyscus maniculatus). We first show that long-tailed forest mice perform better in an arboreal locomotion assay, consistent with tails being important for balance during climbing. We then identify six genomic regions that contribute to differences in tail length, three of which associate with caudal vertebra length and the other three with vertebra number. For all six loci, the forest allele increases tail length, indicative of the cumulative effect of natural selection. Two of the genomic regions associated with variation in vertebra number contain Hox gene clusters. Of those, we find an allele-specific decrease in Hoxd13 expression in the embryonic tail bud of long-tailed forest mice, consistent with its role in axial elongation. Additionally, we find that forest embryos have more presomitic mesoderm than prairie embryos and that this correlates with an increase in the number of neuromesodermal progenitors, which are modulated by Hox13 paralogues. Together, these results suggest a role for Hoxd13 in the development of natural variation in adaptive morphology on a microevolutionary timescale.
Asunto(s)
Proteínas de Homeodominio , Peromyscus , Factores de Transcripción , Animales , Bosques , Peromyscus/genética , Selección Genética , Factores de Transcripción/genética , Proteínas de Homeodominio/genética , Cola (estructura animal)RESUMEN
The origin of novel traits, those that are not direct modifications of a pre-existing ancestral structure, remains a fundamental problem in evolutionary biology. For example, little is known about the evolutionary and developmental origins of the novel avian vocal organ, the syrinx. Located at the tracheobronchial junction, the syrinx is responsible for avian vocalization, but it is unclear whether avian vocal folds are homologous to the laryngeal vocal folds in other tetrapods or convergently evolved. Here, we identify a core developmental program involved in avian vocal fold formation and infer the morphology of the syrinx of the ancestor of modern birds. We find that this ancestral syrinx had paired sound sources induced by a conserved developmental pathway and show that shifts in these signals correlate with syringeal diversification. We show that, despite being derived from different developmental tissues, vocal folds in the syrinx and larynx have similar tissue composition and are established through a strikingly similar developmental program, indicating that co-option of an ancestral developmental program facilitated the origin of vocal folds in the avian syrinx.
Asunto(s)
Laringe , Pliegues Vocales , Animales , Pliegues Vocales/anatomía & histología , Laringe/anatomía & histología , Aves/anatomía & histología , Tráquea/anatomía & histología , Sonido , Vocalización AnimalRESUMEN
In its most basic conception, a novelty is simply something new. However, when many previously proposed evolutionary novelties have been illuminated by genetic, developmental, and fossil data, they have refined and narrowed our concept of biological "newness." For example, they show that these novelties can occur at one or multiple levels of biological organization. Here, we review the identity of structures in the avian vocal organ, the syrinx, and bring together developmental data on airway patterning, structural data from across tetrapods, and mathematical modeling to assess what is novel. In contrast with laryngeal cartilages that support vocal folds in other vertebrates, we find no evidence that individual cartilage rings anchoring vocal folds in the syrinx have homology with any specific elements in outgroups. Further, unlike all other vertebrate vocal organs, the syrinx is not derived from a known valve precursor, and its origin involves a transition from an evolutionary "spandrel" in the respiratory tract, the site where the trachea meets the bronchi, to a target for novel selective regimes. We find that the syrinx falls into an unusual category of novel structures: those having significant functional overlap with the structures they replace. The syrinx, along with other evolutionary novelties in sensory and signaling modalities, may more commonly involve structural changes that contribute to or modify an existing function rather than those that enable new functions.
Asunto(s)
Evolución Biológica , Aves/anatomía & histología , Aves/fisiología , Tráquea/anatomía & histología , Animales , Fósiles , Laringe/anatomía & histología , Laringe/fisiología , Filogenia , Sistema Respiratorio/anatomía & histología , Tráquea/fisiología , Pliegues Vocales , Vocalización AnimalRESUMEN
Understanding both the role of selection in driving phenotypic change and its underlying genetic basis remain major challenges in evolutionary biology. Here, we use modern tools to revisit a classic system of local adaptation in the North American deer mouse, Peromyscus maniculatus, which occupies two main habitat types: prairie and forest. Using historical collections, we find that forest-dwelling mice have longer tails than those from nonforested habitat, even when we account for individual and population relatedness. Using genome-wide SNP data, we show that mice from forested habitats in the eastern and western parts of their range form separate clades, suggesting that increased tail length evolved independently. We find that forest mice in the east and west have both more and longer caudal vertebrae, but not trunk vertebrae, than nearby prairie forms. By intercrossing prairie and forest mice, we show that the number and length of caudal vertebrae are not correlated in this recombinant population, indicating that variation in these traits is controlled by separate genetic loci. Together, these results demonstrate convergent evolution of the long-tailed forest phenotype through two distinct genetic mechanisms, affecting number and length of vertebrae, and suggest that these morphological changes-either independently or together-are adaptive.
Asunto(s)
Evolución Biológica , Peromyscus/anatomía & histología , Peromyscus/genética , Fenotipo , Cola (estructura animal)/anatomía & histología , Animales , ADN Mitocondrial/genética , Bosques , Pradera , América del Norte , Filogeografía , Análisis de Secuencia de ADNRESUMEN
PURPOSE: To examine whether patients with mild traumatic brain injury (mTBI) receiving text messaging-based education and behavioral support had fewer and less severe postconcussive symptoms than those not receiving text-message support. Our secondary objective was to determine the feasibility of using text messaging to assess daily symptoms and provide support to patients with mTBI. DESIGN: Randomized controlled trial with 14-day follow-up. PARTICIPANTS: Convenience sample of 43 adult emergency department patients with mTBI. INTERVENTION: Fourteen days of timed SMS (short-message service) symptom assessments (9 AM: headaches; 1 PM: difficulty concentrating; 5 PM: irritability or anxiety) with self-care support messages. MAIN MEASURES: SMS symptom reports, Rivermead Postconcussion Symptoms Questionnaire. RESULTS: Compared with the control group, intervention participants trended to lower odds of reporting headaches (odds ratio [OR] = 0.38; 95% confidence interval [CI]: 0.07-1.99), concentration difficulty (OR = 0.32; 95% CI: 0.04-2.24), and irritability or anxiety (OR = 0.33; 95% CI: 0.05-2.35). There were also trends of lower mean scores for headaches (0.99 vs 1.19; P = .5), difficulty concentrating (0.88 vs 1.23; P = .2), and irritability/anxiety (1.00 vs 1.62; P = .06). There were high response rate to SMS symptom assessments and high satisfaction with the intervention. CONCLUSION: Those receiving the text messaging-based education and support had fewer and less severe postconcussive symptoms than the controls but none of the differences reached statistical significance. Further evaluation of more robust mobile interventions and larger sample of participants are still needed.
Asunto(s)
Lesiones Encefálicas/terapia , Teléfono Celular/estadística & datos numéricos , Educación del Paciente como Asunto/métodos , Autocuidado/métodos , Envío de Mensajes de Texto , Adulto , Lesiones Encefálicas/diagnóstico , Servicio de Urgencia en Hospital , Femenino , Estudios de Seguimiento , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Monitoreo Fisiológico/métodos , Proyectos Piloto , Síndrome Posconmocional/diagnóstico , Síndrome Posconmocional/terapia , Valores de Referencia , Medición de Riesgo , Método Simple Ciego , Encuestas y Cuestionarios , Factores de Tiempo , Adulto JovenRESUMEN
Adaptation is a central focus of biology, although it can be difficult to identify both the strength and agent of selection and the underlying molecular mechanisms causing change. We studied cryptically colored deer mice living on the Nebraska Sand Hills and show that their light coloration stems from a novel banding pattern on individual hairs produced by an increase in Agouti expression caused by a cis-acting mutation (or mutations), which either is or is closely linked to a single amino acid deletion in Agouti that appears to be under selection. Furthermore, our data suggest that this derived Agouti allele arose de novo after the formation of the Sand Hills. These findings reveal one means by which genetic, developmental, and evolutionary mechanisms can drive rapid adaptation under ecological pressure.
Asunto(s)
Adaptación Fisiológica/genética , Proteína de Señalización Agouti/genética , Alelos , Evolución Molecular , Color del Cabello/genética , Peromyscus/genética , Pigmentación/genética , Proteína de Señalización Agouti/química , Animales , Cruzamientos Genéticos , Ecosistema , Frecuencia de los Genes , Cabello/química , Cabello/crecimiento & desarrollo , Haplotipos , Desequilibrio de Ligamiento , Melaninas/análisis , Datos de Secuencia Molecular , Mutación , Nebraska , Peromyscus/fisiología , Fenotipo , Polimorfismo Genético , ARN Mensajero/genética , ARN Mensajero/metabolismo , Selección Genética , Eliminación de Secuencia , Serina/genéticaRESUMEN
Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought.
Asunto(s)
Proteína de Señalización Agouti/genética , Melanosis/genética , Mutación , Peromyscus/genética , Animales , Cromosomas Artificiales Bacterianos , Genes Recesivos , Hibridación in Situ , Reacción en Cadena de la Polimerasa , Receptor de Melanocortina Tipo 1/genética , Eliminación de Secuencia , Especificidad de la EspecieRESUMEN
During animal development, blast cell lineages are generated by repeated divisions of a mother cell into a series of daughter cells, often with a specific series of distinct fates. Nanos is a translational regulator that is involved in germline development in diverse animals and also involved in somatic patterning in insects. Recently, Nanos was found to be required for maintenance of stem cell divisions in the Drosophila germline. We have found that in the mollusk Ilyanassa, Nanos messenger RNA and protein are specifically localized in the mesendodermal blast cell lineage derived from the strongly conserved 4d cell. Nanos activity is required for differentiation of multiple tissues that are derived from the 4d cell, showing that IoNanos is required for somatic development in this embryo. At the cellular level, we show that IoNanos activity is required for the highly stereotyped cleavage pattern of the 4d lineage, the proliferative capacity of the blast cells, and the marked asymmetry of the blast cell divisions. These results suggest that IoNanos is involved in regulating blast cell behaviors in the 4d lineage.
Asunto(s)
Diferenciación Celular , Linaje de la Célula/fisiología , Embrión no Mamífero/metabolismo , Caracoles/embriología , Animales , Proteínas de Drosophila/metabolismo , Proteínas de Unión al ARN/metabolismo , Caracoles/metabolismoRESUMEN
Asymmetric cell divisions are a crucial mode of cell fate specification in multicellular organisms, but their relative contribution to early embryonic patterning varies among taxa. In the embryo of the mollusc Ilyanassa, most of the early cell divisions are overtly asymmetric. During Ilyanassa early cleavage, mRNAs for several conserved developmental patterning genes localize to interphase centrosomes, and then during division they move to a portion of the cortex that will be inherited by one daughter cell. Here we report an unbiased survey of RNA localization in the Ilyanassa embryo, and examine the overall patterns of centrosomal localization during early development. We find that 3-4% of RNAs are specifically localized to centrosomes during early development, and the remainder are either ubiquitously distributed throughout the cytoplasm or weakly enriched on centrosomes compared with levels in the cytoplasm. We observe centrosomal localization of RNAs in all cells from zygote through the fifth cleavage cycle, and asymmetric RNA segregation in all divisions after the four-cell stage. Remarkably, each specifically localized message is found on centrosomes in a unique subset of cells during early cleavages, and most are found in unique sets of cells at the 24-cell stage. Several specifically localized RNAs are homologous to developmental regulatory proteins in other embryos. These results demonstrate that the mechanisms of localization and segregation are extraordinarily intricate in this system, and suggest that these events are involved in cell fate specification across all lineages in the early Ilyanassa embryo. We propose that greater reliance on segregation of determinants in early cleavage increases constraint on cleavage patterns in molluscs and other spiralian groups.
Asunto(s)
ARN/metabolismo , Caracoles/embriología , Animales , Centrosoma/metabolismo , Embrión no Mamífero/embriología , Embrión no Mamífero/metabolismo , ARN/genética , Caracoles/genética , Caracoles/metabolismoRESUMEN
Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessive disorder of childhood caused by mutations in CLN3. Although visual deterioration is typically the first clinical sign to manifest in affected children, loss of Cln3 in a mouse model of JNCL does not recapitulate this retinal deterioration. This suggests that either the loss of CLN3 does not directly affect retinal cell survival or that nuclei involved in visual processing are affected prior to retinal degeneration. Having previously demonstrated that Cln3(-/-) mice have decreased optic nerve axonal density, we now demonstrate a decrease in nerve conduction. Examination of retino-recipient regions revealed a decreased number of neurons within the dorsal lateral geniculate nucleus (LGNd). We demonstrate decreased transport of amino acids from the retina to the LGN, suggesting an impediment in communication between the retina and projection nuclei. This study defines a novel path of degeneration within the LGNd, providing a mechanism for causation of JNCL visual deficits.
Asunto(s)
Cuerpos Geniculados/fisiopatología , Glicoproteínas de Membrana/genética , Chaperonas Moleculares/genética , Lipofuscinosis Ceroideas Neuronales/fisiopatología , Enfermedades del Nervio Óptico/fisiopatología , Degeneración Retiniana/fisiopatología , Animales , Transporte Axonal/genética , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo/genética , Femenino , Cuerpos Geniculados/metabolismo , Cuerpos Geniculados/patología , Masculino , Ratones , Ratones Noqueados , Mutación/genética , Degeneración Nerviosa/genética , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/metabolismo , Nervio Óptico/metabolismo , Nervio Óptico/patología , Nervio Óptico/fisiopatología , Enfermedades del Nervio Óptico/genética , Enfermedades del Nervio Óptico/metabolismo , Degeneración Retiniana/genética , Degeneración Retiniana/metabolismo , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , Baja Visión/genética , Baja Visión/metabolismo , Baja Visión/fisiopatologíaRESUMEN
PURPOSE: Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten Disease) is one of the most common progressive neurodegenerative disorders of childhood, resulting from autosomal recessive inheritance of mutations in the CLN3 gene. Pathologically, Batten disease is characterized by lysosomal storage of autofluorescent material in all tissue types. Although characterized by seizures, mental retardation, and loss of motor skills, the first presenting symptom of Batten disease is vision loss. METHODS: High-density oligonucleotide arrays were used to profile approximately 19,000 mRNAs in the eye of 10-week-old Cln3-knockout and normal mice, and the data were compared with that for the cerebellum in the same model as a means to identify gene expression changes that are specific to the eye. RESULTS: A detailed list was compiled of 285 functionally categorized genes that have altered expression in the eye of Cln3-knockout mice before the appearance of the characteristic lysosomal storage material. Furthermore, 18 genes were identified and 6 validated by semiquantitative RT-PCR that have altered expression in the eye, but not in the cerebellum of Cln3-knockout mice. The genes that have altered expression specific to the eye of the Cln3-knockout mouse may be of importance in understanding the function of CLN3 in different tissues. CONCLUSIONS: Downregulation of genes associated with energy production in the mitochondria appears to be specific to the eye. The CLN3 defect may result in altered mitochondrial function in eye but not other tissue. More detailed experimentation is needed to understand the contribution of these changes in expression to disease state, and whether these changes are specific for certain cell types within the eye.