Inner Ear Genes Underwent Positive Selection and Adaptation in the Mammalian Lineage

The mammalian inner ear possesses functional and morphological innovations that contribute to its unique hearing capacities. The genetic bases underlying the evolution of this mammalian landmark are poorly understood. We propose that the emergence of morphological and functional innovations in the mammalian inner ear could have been driven by adaptive molecular evolution. In this work, we performed a meta-analysis of available inner ear gene expression data sets in order to identify genes that show signatures of adaptive evolution in the mammalian lineage. We analyzed ∼1,300 inner ear expressed genes and found that 13% show signatures of positive selection in the mammalian lineage. Several of these genes are known to play an important function in the inner ear. In addition, we identified that a significant proportion of genes showing signatures of adaptive evolution in mammals have not been previously reported to participate in inner ear development and/or physiology. We focused our analysis in two of these genes: STRIP2 and ABLIM2 by generating null mutant mice and analyzed their auditory function. We found that mice lacking Strip2 displayed a decrease in neural response amplitudes. In addition, we observed a reduction in the number of afferent synapses, suggesting a potential cochlear neuropathy. Thus, this study shows the usefulness of pursuing a high-throughput evolutionary approach followed by functional studies to track down genes that are important for inner ear function. Moreover, this approach sheds light on the genetic bases underlying the evolution of the mammalian inner ear.Fil: Pisciottano, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Cinalli, Alejandro Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Stopiello, Juan Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Castagna, Valeria Carolina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Gomez Casati, Maria Eugenia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Franchini, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

A nervous system enhancer underwent accelerated evolution in primates and shows heterochrony during brain development in transgenic mice

A nervous system enhancer underwent accelerated evolution in primates and shows heterochrony during brain development in transgenic mice.Stopiello, J.M., López-Leal R., Rubinstein, M and Franchini, L.F.The lineage leading to humans underwent an expansion in cortical brain size which is, at least in part, responsible for the particular cognitive abilities of primates and particularly of humans. Aiming to identify the genetic elements that underlie brain evolution in primates, we found a 400 bp region that shows signatures of acceleration in the primate lineage and that we have named AANC. In contrast, the gene that is regulated by AANC shows a very high conservation from insects to mammals and shows no sign of acceleration in the primate lineage. This gene is key for neurogenesis during the development of the central nervous system (CNS).Using a transgenic reporter assay in mouse and zebrafish, we tested the ability of the murine AANC to act as an enhancer in the CNS during development. We found that mouse AANC drives, in a very specific manner, reporter expression to the ventricular zone of the mouse neocortex during neurogenesis. In order to understand the biological meaning of the DNA changes that occurred in AANC in primates, we conducted transgenic reporter assays in mouse using the human AANC. We conclude that human AANC can expand the spatial and temporal expression of the reporter activity in mouse compared to murine AANC. This works shows that AANC is a strong brain developmental enhancer which expanded its temporal and spatial expression pattern in primates and help us to understand genetic and molecular mechanisms that could be important in primate brain evolution.Fil: Stopiello, Juan Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: López Leal, Rodrigo. Centro de Estudios Científicos; ChileFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Franchini, Lucia Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaII FALAN Congress; XV Jornadas de la Sociedad de Neurociencias del Uruguay XII Reunión Anual de la Sociedad Chilena de Neurociencias; XXXI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; XXXIX Reunião Anual da la Sociedade Brasileira de Neurociências e Comportamento.Ciudad Autónoma de Buenos AiresArgentinaFederación de Asociaciones Latinoamericanas y del Caribe de NeurocienciasSociedad Argentina de Investigación en Neurociencia