Lynx conservation genomics: evaluating functional variation and the role of natural selection in declining populations
Genómica de la conservación de linces: evaluación de la variación funcional y del papel de la selección en poblaciones en declive
Principal investigator
José Antonio Godoy
Financial institution
MIN ECONOMÍA Y COMPETITIVIDAD
Fecha de inicio
Fecha de fin
Code
CGL2013-47755-P
Department
Ecology and Evolution
Brief description
Durante las últimas dos décadas los estudios de genética de conservación han mostrado cómo las poblaciones en declive y aisladas pierden la diversidad genética, acumulan consanguinidad y se diferencian de otras poblaciones, y en algunos casos resultan en reducciones de fitness. Además, se asume que una diversidad genética reducida se traduce en una menor capacidad de las poblaciones para adaptarse a los cambios ambientales. Sin embargo, estos estudios se han basado casi exclusivamente en el uso de unos pocos marcadores moleculares neutrales y secuencias mitocondriales. Queda pues la duda de en qué medida estos patrones reflejan la variación genómica global y, lo que es más importante, el componente funcional del que tanto el potencial de adaptación como el fitness dependen. El lince ibérico (Lynx pardinus) ofrece un modelo único para el estudio de la variación genómica funcional en poblaciones en declive, ya que i) ha sufrido un declive bien documentado que ha afectado a su variación genética y, en última instancia, al fitness, ii) tenemos disponible una amplia colección de más de 500 muestras, incluyendo ca . 200 muestras históricas, que proporcionan una buena cobertura geográfica y temporal , iii) se ha acumulado una abundante información fenotípica y genealógica, generada por los programas de investigación y de gestión actuales y pasados, y iv) un reciente proyecto liderado por el IP ha generado los recursos genómicos necesarios, incluyendo un genoma anotado de referencia. Además, su especie hermana, el lince boreal (Lynx lynx), también ha pasado por un proceso de contracción y fragmentación en Europa occidental que ha generado una serie de poblaciones que extenderán y replicarán el rango de escenarios demográficos y genéticos cubiertos por el lince ibérico. El objetivo de este proyecto es por tanto evaluar las consecuencias de la reciente disminución y fragmentación de las poblaciones de lince en la variación genómica funcional y el papel de la selección natural en el mantenimiento de la diversidad adaptativa y en la acumulación de alelos deletéreos (i.e. la carga genética). Para ello obtendremos secuencias genómicas correspondientes a exones y regiones intergénicas a través de la secuenciación NGS de librerías enriquecidas. Compararemos los patrones de variación en loci supuestamente neutrales (regiones intergénicas) y funcionales (exones) en poblaciones con distinta historia demográfica y edades, buscaremos señales de selección balanceadora y purificadora en las distintos loci secuenciados, y estimaremos la carga genética mediante la identificación de alelos potencialmente deletéreos. Los loci identificados como candidatos de estar sometidos a la acción reciente de la selección balanceadora y los que se identifiquen como portadores de variantes perjudiciales serán estudiados sobre muestras poblacionales ampliadas y sobre genealogías conocidas para poner a prueba estas hipótesis. La presente propuesta se convertirá en uno de los primeros estudios genómicos en especies en peligro de extinción hasta la fecha, e intentará responder a dos preguntas básicas del paradigma de la genética de la conservación, i.e.: i ) ¿hasta qué punto se ve afectada la variación genética adaptativa en poblaciones pequeñas y aisladas? , y ii ) ¿cuáles son los mecanismos que conectan los patrones y la dinámica de la variación genética con el fitness y la adaptación?
During the last two decades conservation genetics studies have extensively confirmed that declining and isolated populations lose genetic diversity, accumulate inbreeding and differentiate from other populations. Some studies have also shown concomitant fitness reductions in genetically eroded populations, and it is often assumed that lower diversity translate into a lower potential of these populations to adapt to environmental change. However, these studies have been almost exclusively based on the use of a few neutral molecular markers (e.g. nuclear microsatellites) and mitochondrial sequences. The question remains to which extent patterns at a few neutral markers reflect genome-wide patterns and, even more importantly, the functional variation on which both adaptive potential and fitness depend. The Iberian lynx (Lynx pardinus) provides a unique model on which to study these issues, as i) it has gone through a well documented decline that has affected genetic variation and eventually fitness, ii) a broad collection of more than 500 samples is already available, including ca. 200 historical samples, which provide a good geographical and temporal coverage, iii) extensive phenotypic and genealogical information has accumulated through the output of past and ongoing research and management programs, and iv) a recent project lead by the IP has generated the genomic resources required, including an annotated reference genome. Furthermore, its sister species, the Eurasian lynx (Lynx lynx), has also gone through a process of contraction and fragmentation in western Europe that has generated an array of populations that will extend and replicate the range of demographic and genetic scenarios covered by the Iberian lynx. The goal of the present project is to evaluate the consequences of recent decline and fragmentation of lynx populations on functional genomic variation and to assess how natural selection might have influenced the maintenance of functional diversity and the accumulation deleterious alleles (i.e. the genetic load). We will obtain genomic sequences corresponding to exons and intergenic regions in samples of a range of Iberian and Eurasian lynx populations, including historical and ancient samples, through NGS sequencing of target-enriched libraries. We will compare variation patterns at assumed neutral (intergenic) and functional (exons) loci across populations and through time, search for signals of balancing and purifying selection across loci, and estimate the genetic load across populations by identifying potentially deleterious alleles through the prediction of the functional impact of segregating variants. Loci identified as candidates for the recent or ongoing action of balancing selection, and those identified as carrying severely detrimental variants will be further studied in larger population samples and genealogies to test these hypothesis. The present proposal will become one of the first genomic studies in highly endangered species to date, so it is expected to yield novel and valuable insights on the genomic basis of genetic erosion occurring in declining populations. In particular, it aims at answering two basic questions of the conservation genetics paradigm, i.e. i) to what extent is selectively important genetic variation affected in small, isolated populations?, and ii) what are the mechanisms that connect the patterns and dynamics of genetic variation with fitness and adaptation?
During the last two decades conservation genetics studies have extensively confirmed that declining and isolated populations lose genetic diversity, accumulate inbreeding and differentiate from other populations. Some studies have also shown concomitant fitness reductions in genetically eroded populations, and it is often assumed that lower diversity translate into a lower potential of these populations to adapt to environmental change. However, these studies have been almost exclusively based on the use of a few neutral molecular markers (e.g. nuclear microsatellites) and mitochondrial sequences. The question remains to which extent patterns at a few neutral markers reflect genome-wide patterns and, even more importantly, the functional variation on which both adaptive potential and fitness depend. The Iberian lynx (Lynx pardinus) provides a unique model on which to study these issues, as i) it has gone through a well documented decline that has affected genetic variation and eventually fitness, ii) a broad collection of more than 500 samples is already available, including ca. 200 historical samples, which provide a good geographical and temporal coverage, iii) extensive phenotypic and genealogical information has accumulated through the output of past and ongoing research and management programs, and iv) a recent project lead by the IP has generated the genomic resources required, including an annotated reference genome. Furthermore, its sister species, the Eurasian lynx (Lynx lynx), has also gone through a process of contraction and fragmentation in western Europe that has generated an array of populations that will extend and replicate the range of demographic and genetic scenarios covered by the Iberian lynx. The goal of the present project is to evaluate the consequences of recent decline and fragmentation of lynx populations on functional genomic variation and to assess how natural selection might have influenced the maintenance of functional diversity and the accumulation deleterious alleles (i.e. the genetic load). We will obtain genomic sequences corresponding to exons and intergenic regions in samples of a range of Iberian and Eurasian lynx populations, including historical and ancient samples, through NGS sequencing of target-enriched libraries. We will compare variation patterns at assumed neutral (intergenic) and functional (exons) loci across populations and through time, search for signals of balancing and purifying selection across loci, and estimate the genetic load across populations by identifying potentially deleterious alleles through the prediction of the functional impact of segregating variants. Loci identified as candidates for the recent or ongoing action of balancing selection, and those identified as carrying severely detrimental variants will be further studied in larger population samples and genealogies to test these hypothesis. The present proposal will become one of the first genomic studies in highly endangered species to date, so it is expected to yield novel and valuable insights on the genomic basis of genetic erosion occurring in declining populations. In particular, it aims at answering two basic questions of the conservation genetics paradigm, i.e. i) to what extent is selectively important genetic variation affected in small, isolated populations?, and ii) what are the mechanisms that connect the patterns and dynamics of genetic variation with fitness and adaptation?