Publication: Models in molecular evolution: the case of toyLIFE
Loading...
Identifiers
Publication date
2017-03
Defense date
2017-03-24
Authors
Advisors
Tutors
Journal Title
Journal ISSN
Volume Title
Publisher
Impact
Export
Abstract
This thesis set out to contribute to the growing body of knowledge pertaining
models of the genotype-phenotype map. In the process, we proposed
and studied a new computational model, toyLIFE, and a new metaphor for
molecular evolution —adaptive multiscapes. We also studied functional
promiscuity and the evolutionary dynamics of shifting environments.
The first result of this thesis was the definition of toyLIFE, a simplified
model of cellular biology that incorporated toy versions of genes, proteins
and regulation as well as metabolic laws. Molecules in toyLIFE interact
between 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, with
complex regulatory and metabolic networks that grew in complexity as the
genome 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 metabolic
networks. All of these models either disregarded cellular context when assigning
phenotype and function (RNA and proteins) or omitted genome
dynamics, by defining their genotypes from high-level abstractions (GRNs
and metabolic networks). toyLIFE shares the same features exhibited by all
genotype-phenotype maps studied so far. There is strong degeneracy in the
map, with many genotypes mapping into the same phenotype. This degeneracy
translates into the existence of neutral networks, that span genotype
space as soon as the genotype contains more than two genes. There is also
a 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 to
perform more than one function) in computational models of the genotypephenotype
map. 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 biology
as a neatly functioning machine. One of the most interesting results of
this thesis came from studying the evolutionary dynamics of shifting environments
in populations showing functional promiscuity: our results show
that there is an optimal frequency of change that minimizes the time to
extinction of the population.
Finally, we presented a new metaphor for molecular evolution: adaptive
multiscapes. This framework intends to update the fitness landscape
metaphor proposed by Sewall Wright in the 1930s. Adaptive multiscapes
include many features that we have learned from computational studies of
the genotype-phenotype map, and that have been discussed throughout the
thesis. The existence of neutral networks, the asymmetry in phenotype
sizes -and the concomitant asymmetry in phenotype accessibility- and the
presence of functional promiscuity all alter the original fitness landscape
picture.
Description
Mención Internacional en el tÃtulo de doctor
Keywords
Genotype-phenotype map, Computational model, ToyLIFE, Bioinformática