Publication: Estudio evolutivo de los intrones del MHC en aves passeriformes del género Carduelis
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2021-07-09
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Universidad Complutense de Madrid
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Abstract
El Complejo Principal de Histocompatibilidad (CPH, en inglés MHC, Major Histocompatibility Complex) está formado por un conjunto de genes mayoritariamente polimórficos, cuyos productos se expresan en la superficie de gran variedad de células los cuales son los responsables de la respuesta inmune adaptativa. El mejor MHC estudiado en aves es el de Gallus gallus, el cual se encuentra ubicado en el microcromosoma 16 y está formado por la región MHC-B y la región MHC-Y. Estas regiones se caracterizan por contener genes muy próximos entre sí y poseer intrones muy cortos, lo que lleva a plantear la hipótesis del MHC “mínimo esencial” que defiende que este sistema contiene sólo el mínimo número de genes absolutamente esenciales para la función del MHC en un sentido evolutivo. El estudio de estos genes de histocompatibilidad en aves pertenecientes al orden Passeriformes es importante porque a estas aves se les consideran modelos naturales en los que la evolución del polimorfismo del MHC ha sido adquirida a lo largo de millones de años. Por ello, es interesante comparar este polimorfismo con el de modelos artificiales como el pollo, el ser humano o el ratón en los que poblaciones pequeñas han crecido rápidamente por consanguinidad y se han convertido en poblaciones relativamente grandes. Otro argumento a favor del estudio del MHC de estas aves es que es fácil identificar las especies y es muy cómodo manejar estas muestras. Además, presentan una amplia distribución geográfica y hay un gran número de especies pertenecientes a este orden. Los intrones son fragmentos de ADN localizados dentro de un gen, que no codifican ningún fragmento de la proteína, ya que son eliminados en el proceso de maduración del ARN. La presencia de intrones en el genoma es una característica propia de los organismos eucariotas, aunque algunos procariotas también presentan intrones en su material genético. A día de hoy, se pueden describir 8 tipos de intrones. Tradicionalmente, se ha defendido que los intrones son fragmentos de ADN carentes de información cuya presencia en los genomas supone una carga para la célula. Sin embargo, en la actualidad, se ha demostrado que los intrones presentan un amplio espectro de funciones y están involucrados en cada paso del procesamiento de ARNm.
La realización de este trabajo tiene el objetivo fundamental de analizar el polimorfismo y la evolución del MHC en especies del género Carduelis a través del estudio del intrón 2 de estos genes. El análisis de estos intrones nos puede dar una idea de si éstos cumplen una función esencial en el MHC que ha hecho que se hayan mantenido sin apenas variación a lo largo de millones de años. Además, el análisis filogenético de estas especies que se ha llevado a cabo en este trabajo nos permite estudiar la evolución molecular del MHC y compararla con las relaciones filogenéticas de estos jilgueros mediante el estudio del gen del citocromo b. Para estudiar la filogenia se emplean dos métodos de reconstrucción de árboles filogenéticos: Máxima verosimilitud o Maximum likelihood (ML) e Inferencia Bayesiana (IB)...
The Major Histocompatibility Complex (MHC) comprises the most polymorphic loci in vertebrates and its molecules present antigenic peptides to clonotypic T cell receptor in order to start an immune response. The chicken’s MHC is the best-studied MHC in birds. It is located in microchromosome 16 and it is formed of MHC-B region and MHC-Y region. These regions are characterized by containing genes that are very close to each other and by having very short introns; that supported the hypothesis that the chicken’s MHC represented a ‘minimal essential MHC’. The study of these genes in birds that belong to order Passeriformes is important because these birds are considered natural models in which evolution of MHC polymorphism has been acquired over millions of years. Therefore, it is interesting to compare this polymorphism with artificial models such as chicken, human or mouse in which small populations have grown rapidly by consanguinity and they have become relatively large populations. Another argument in favor of MHC study in these birds is that it is easy to identify species and it is very convenient to handle these samples. In addition, they have a wide geographical distribution and there is a large number of species belonging to this order. Introns are DNA fragments located within a gene, which do not encode any part of the protein and they are eliminated in RNA maturation. The presence of introns in genome is an own characteristic of eukaryotic organisms, although some prokaryotes also have introns in their genetic material. Today, eight types of introns are described. Traditionally, it has been argued that introns are DNA fragments lacking information whose presence in genomes is a burden on the cell. However, at present, it has been shown introns present a broad spectrum of functions and they are involved in each step of mRNA processing. In the present work, we have aimed to analyze MHC polymorphism and evolution in species of genus Carduelis through intron 2 study of these genes. Our analysis of these introns can give us an idea of whether they fulfill an essential function in the MHC that has kept them with not much variation over millions of years. As well, phylogenetic analysis of these species allow us to study MHC molecular evolution and compare it with phylogenetic relationships of these goldfinches through study of cytochrome b gene sequence. To study phylogeny, two methods for reconstructing phylogenetic trees were used: Maximum likelihood (ML) and Bayesian Inference (BI)...
The Major Histocompatibility Complex (MHC) comprises the most polymorphic loci in vertebrates and its molecules present antigenic peptides to clonotypic T cell receptor in order to start an immune response. The chicken’s MHC is the best-studied MHC in birds. It is located in microchromosome 16 and it is formed of MHC-B region and MHC-Y region. These regions are characterized by containing genes that are very close to each other and by having very short introns; that supported the hypothesis that the chicken’s MHC represented a ‘minimal essential MHC’. The study of these genes in birds that belong to order Passeriformes is important because these birds are considered natural models in which evolution of MHC polymorphism has been acquired over millions of years. Therefore, it is interesting to compare this polymorphism with artificial models such as chicken, human or mouse in which small populations have grown rapidly by consanguinity and they have become relatively large populations. Another argument in favor of MHC study in these birds is that it is easy to identify species and it is very convenient to handle these samples. In addition, they have a wide geographical distribution and there is a large number of species belonging to this order. Introns are DNA fragments located within a gene, which do not encode any part of the protein and they are eliminated in RNA maturation. The presence of introns in genome is an own characteristic of eukaryotic organisms, although some prokaryotes also have introns in their genetic material. Today, eight types of introns are described. Traditionally, it has been argued that introns are DNA fragments lacking information whose presence in genomes is a burden on the cell. However, at present, it has been shown introns present a broad spectrum of functions and they are involved in each step of mRNA processing. In the present work, we have aimed to analyze MHC polymorphism and evolution in species of genus Carduelis through intron 2 study of these genes. Our analysis of these introns can give us an idea of whether they fulfill an essential function in the MHC that has kept them with not much variation over millions of years. As well, phylogenetic analysis of these species allow us to study MHC molecular evolution and compare it with phylogenetic relationships of these goldfinches through study of cytochrome b gene sequence. To study phylogeny, two methods for reconstructing phylogenetic trees were used: Maximum likelihood (ML) and Bayesian Inference (BI)...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 08/02/2021