Year: 2021
Type: dissertation
Abstract: Over the last years we have come to realize that the history of our species is not as simple as we once thought. We are now faced with complex demographic scenarios, events of admixture with human species and the realization that our differences with Neanderthals might be of gradient, not quality. Knowing all of this, we have to face the question of what did in fact change since the emergence of our species, to what extent, when did it happened in our evolution, and what consequences those changes bring for complex traits. This thesis tries to contribute answers to these questions, either through in silico analysis of open, publicly available genomic databases, or, when possible, in vitro, in collaboration with other research groups. \nChapter 1 outlines the questions that are treated in this thesis and summarizes the results and arguments of each chapter. First, I present an overview of the current understanding of human evolution since the split between the Neanderthal/Denisovan lineage and the Homo sapiens branch. Then, I show what kind of core questions arise from the state of the field, namely what can be done to explore the relationship between genotype and phenotype over evolutionary time in humans. I follow with a succinct summary of the main methods and results of each chapter, showing how they try to answer each of these questions, as well as a final note on challenges and future steps. \nChapter 2 explores the effects of Homo sapiens variants in gene expression in specific brain tissues, using the GTEx consortium eQTL database. We highlight the effect of regulation in human evolution, present contrasts with previous literature regarding directional gene regulation, and presents genes that correlate with brain volume GWAS signals. \nChapter 3 presents the result of our collaboration with the team of Dr. Giuseppe Testa, showing how neurodevelopmental disease modeling can inform our understanding of human evolution. We show how BAZ1B, a gene implicated in Williams-Beuren syndrome, regulates neural crest stem cell induction and migration. Our work suggests that the BAZ1B regulatory network has undergone changes in human evolution, shaping the facial morphology of our species and validating previously-standing hypothesis about the biology of craniofacial morphology in humans. \nChapter 4 applies an open large-scale database of allele age estimations (GEVA) to Homo sapiens specific variants in order to map species-specific genetic variation over time. We also apply gene expression predictions via machine learning and other time-sensitive genomic analysis,and present genes that have undergone changes in specific windows of human evolution.
Author: Muñoz Andirkó, Alejandro Gregorio
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Fundación BBVA, Ministry of Education, Culture, Sports, Science and Technology, Generalitat de Catalunya, Ministerio de Economía y Competitividad, Ministerio de Ciencia e Innovación, Banco Bilbao Vizcaya Argentaria, Fundació Bosch i Gimpera, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, National Institutes of Health, Japan Society for the Promotion of Science, Departament d'Empresa i Coneixement, Generalitat de Catalunya, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Common Fund
OpenAlex ID: W7068070765