Search bioRxivSearch

Biology subjects

Luca Ferretti

Publications and source records attributed to Luca Ferretti.

4 recordsLinked to original sources

A catalogue of Bilaterian-specific genes - their function and expression profiles in early development

Bilateria constitute a monophyletic group of organisms comprising about 99% of all living animals. Since their initial radiation about 540Mya they have evolved a plethora of traits and body forms allowing them to conquer almost any habitat on earth. There are only few truly uniting and shared morphological features retained across the phylum. Unsurprisingly, also the genetic toolkit of bilateria is highly diverged.\n\nIn the light of this divergence we investigated if a set of Bilaterian-specific genes exists and, beyond this, if such genes are related with respect to function and expression patterns among organisms as distant as fly, worm and fish. Using a conservative pyramidal approach of orthology inference we first employed BLAST to extract a set of protein-coding genes which has orthologs in all major branches of Bilateria, but no homologs in non-Bilaterian species. To characterize the proteins with respect to function, we developed a new method for multi-species GO analysis and augmented it by a human-curated annotation based on an extensive literature search. Finally, we extracted characteristic developmental expression profiles for Bilateria from the detailed data available for three model organisms and we explored the relation between expression and function.\n\nWe find 85 clusters of pan-bilaterian proteins. Although some of these proteins belong to common developmental processes, they cover a wide range of biological components, from transcription factors to metabolic enzymes. The 85 groups include myoD, an important regulator of mesodermal cell fate and muscle development, and prospero and several other factors involved in nervous system development. They reveal a so far unknown connection between bilaterian key innovations (mesoderm, complex nervous system) and the emergence of new genes in the ancestor of bilaterians. In addition, the majority of these genes tends to be highly expressed when the adult body plan is constructed. These observations are compatible with the idea that bilaterians are characterized by the unfolding of an additional developmental phase, namely the transition of the larva to morphologically distinct adults.\n\nAuthor SummaryBilateria represent by far the largest and morphologically most diverse clade of all extant animals. The bilaterian radiation dates back to the so-called Cambrian explosion of species. Although bilateria show a large variety of very distinct body plans, they are also characterized by several common developmental and morphological properties, upon which their monophyly is based. Here, we wanted to know whether these common phenotypic features may also have a common genetic basis, manifested by a set of bilaterian lineage-specific genes. To address this question we compared the proteomes of bilaterian and non-bilaterian species and extracted an initial set of a few hundred candidate proteins. Their underlying genes were further post-processed by means of orthology clustering, multi-species GO enrichment, expression analysis and extensive literature mining. This resulted in a set of 85 clusters of orthologous genes with roles in body morphology-, neuronal system-and muscle development, as well as in cell-cell signalling processes. These genes can be regarded as very promising candidates for further investigation of the genetic basis of a pan-bilaterian pheno-or morphotype and they should be highly interesting targets for functional studies in non-model organisms.

Evolutionary Biology

Measuring epistasis in fitness landscapes: the correlation of fitness effects of mutations

Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness landscapes are high-dimensional, simple measures of their structure are used as statistics in empirical applications. Epistasis is one of the most relevant features of fitness landscapes. Here we propose a new natural measure of the amount of epistasis based on the correlation of fitness effects of mutations. This measure has a natural interpretation, captures well the interaction between mutations and can be obtained analytically for most landscape models. We discuss how this measure is related to previous measures of epistasis (number of peaks, roughness/slope, fraction of sign epistasis, Fourier-Walsh spectrum) and how it can be easily extended to landscapes with missing data or with fitness ranks only. Furthermore, the dependence of the correlation of fitness effects on mutational distance contains interesting information about the patterns of epistasis. This dependence can be used to uncover the amount and nature of epistatic interactions in a landscape or to discriminate between different landscape models.

Evolutionary Biology

Decomposing the site frequency spectrum: the impact of tree topology on neutrality tests

We investigate the dependence of the site frequency spectrum (SFS) on the topological structure of genealogical trees. We show that basic population genetic statistics - for instance estimators of{theta} or neutrality tests such as Tajimas D - can be decomposed into components of waiting times between coalescent events and of tree topology. Our results clarify the relative impact of the two components on these statistics. We provide a rigorous interpretation of positive or negative values of an important class of neutrality tests in terms of the underlying tree shape. In particular, we show that values of Tajimas D and Fay and Wus H depend in a direct way on a peculiar measure of tree balance which is mostly determined by the root balance of the tree. We present a new test for selection in the same class as Fay and Wus H and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulae for these extreme values as a function of sample size and number of segregating sites.

Genetics

MAGELLAN: a tool to explore small fitness landscapes

1In a fitness landscape, fitness values are associated to all genotypes corresponding to several, potentially all, combinations of a set of mutations. In the last decade, many small experimental fitness landscapes have been partially or completely resolved, and more will likely follow. MAGELLAN is a web-based graphical software to explore small fitness/energy landscapes through dynamic visualization and quantitative measures. It can be used to explore input custom landscapes, previously published experimental landscapes or randomly generated model landscapes.

Evolutionary Biology