Elaboração de via de desenvolvimento da glândula mamária e estimativa da origem dos seus genes e do sistema

Abstract

Pathway is a set of hierarchical biological interactions on a biological system. That means that pathways are constituted by nodes, which represent the biological entities, and edges, which represent the hierarchical interactions between those biological entities. Graphical representations of a pathway are of great usefulness because they display the biological information in a concise, intuitive and didactic way. Despite that, there was no pathway describing the development of the mammary gland on any of the main pathway databases, like KEGG Pathway, Reactome or WikiPathways. Another demand regarding the study of the mammary gland refers to the need of elucidating its origin and evolution. Thus, the objective of this work was to create a pathway of the development of the mammary gland and to estimate the origin of its genes and of the system as a whole. For that, the first step consisted in discovering the genes (and the interactions they establish between each other) involved in the development of the mammary gland through text-mining tools, followed by the creation of a graphical pathway and a description for each phase of the glands development (embryonic development, puberty, pregnancy & lactation and involution). Following, the origin of each gene was estimated by determining the lowest common ancestor of the organisms containing copies of each gene, discovered with homologue-clustering tools; the origin of the system was inferred based on the origin of the genes. In this work, four pathways were created, one for each stage of the mammary gland development, which are accompanied by their respective descriptions. Among all of them, 310 genes and 795 biointeractions were found. Gene origin estimation inferred genes originating all the way from the cellular organisms through Boreoeutheria, with 80 to 97% already existing among the fishes (between the clades of Gnathostomata, Teleostomi and Euteleostomi). Comparison between the subpathways revealed that embryonic development and puberty have genes with predicted origin up to Tetrapoda-Amniota, whereas the subpathways of pregnancy & lactation and involution have genes with predicted origin up to Mammalia-Eutheria-Boreoeutheria. This work contributes for the comprehension of the biology and evolution of the mammary gland, as well as provides source material for other studies.