RT Dissertation/Thesis
T1 Models in molecular evolution: the case of toyLIFE
A1 Catalan, Pablo
AB This thesis set out to contribute to the growing body of knowledge pertainingmodels of the genotype-phenotype map. In the process, we proposedand studied a new computational model, toyLIFE, and a new metaphor formolecular evolution —adaptive multiscapes. We also studied functionalpromiscuity and the evolutionary dynamics of shifting environments.The first result of this thesis was the definition of toyLIFE, a simplifiedmodel of cellular biology that incorporated toy versions of genes, proteinsand regulation as well as metabolic laws. Molecules in toyLIFE interactbetween each other following the laws of the HP protein folding model,which endows toyLIFE with a simplified chemistry. From these laws,we saw how something reminiscent of cell-like behavior emerged, withcomplex regulatory and metabolic networks that grew in complexity as thegenome increased.toyLIFE is, to our knowledge, the first multi-level model of the genotype-phenotype map, compared to previous models studied in the literature,such as RNA, proteins, gene regulatory networks (GRNs) or metabolicnetworks. All of these models either disregarded cellular context when assigningphenotype and function (RNA and proteins) or omitted genomedynamics, by defining their genotypes from high-level abstractions (GRNsand metabolic networks). toyLIFE shares the same features exhibited by allgenotype-phenotype maps studied so far. There is strong degeneracy in themap, with many genotypes mapping into the same phenotype. This degeneracytranslates into the existence of neutral networks, that span genotypespace as soon as the genotype contains more than two genes. There is alsoa strong asymmetry in the size distribution of phenotypes: most phenotypes were rare, while a few of them covered most genotypes. Moreover,most common phenotypes are easily accessed from each other.We also studied the prevalence of functional promiscuity (the ability toperform more than one function) in computational models of the genotypephenotypemap. In particular, we studied RNA, Boolean GRNs and toy-LIFE. Our results suggest that promiscuity is the norm, rather than the exception.These results prompt us to rethink our understanding of biologyas a neatly functioning machine. One of the most interesting results ofthis thesis came from studying the evolutionary dynamics of shifting environmentsin populations showing functional promiscuity: our results showthat there is an optimal frequency of change that minimizes the time toextinction of the population.Finally, we presented a new metaphor for molecular evolution: adaptivemultiscapes. This framework intends to update the fitness landscapemetaphor proposed by Sewall Wright in the 1930s. Adaptive multiscapesinclude many features that we have learned from computational studies ofthe genotype-phenotype map, and that have been discussed throughout thethesis. The existence of neutral networks, the asymmetry in phenotypesizes -and the concomitant asymmetry in phenotype accessibility- and thepresence of functional promiscuity all alter the original fitness landscapepicture.
YR 2017
FD 2017-03
LK https://hdl.handle.net/10016/25105
UL https://hdl.handle.net/10016/25105
LA eng
NO Mención Internacional en el título de doctor
DS e-Archivo
RD 18 may. 2024