Search bioRxivSearch

Biology subjects

Thomas Wiehe

Publications and source records attributed to Thomas Wiehe.

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

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

Structure and evolutionary history of a large family of NLR proteins in the zebrafish

Animals and plants have evolved a range of mechanisms for recognizing noxious substances and organisms. A particular challenge, most successfully met by the adaptive immune system in vertebrates, is the specific recognition of potential pathogens, which themselves evolve to escape recognition. A variety of genomic and evolutionary mechanisms shape large families of proteins dedicated to detecting pathogens and create the diversity of binding sites needed for epitope recognition. One family involved in innate immunity are the NACHT-domain-and Leucine-Rich-Repeat-containing (NLR) proteins. Mammals have a small number of NLR proteins, which are involved in first-line immune defense and recognize several conserved molecular patterns. However, there is no evidence that they cover a wider spectrum of differential pathogenic epitopes. In other species, mostly those without adaptive immune systems, NLRs have expanded into very large families. A family of nearly 400 NLR proteins is encoded in the zebrafish genome. They are subdivided into four groups defined by their NACHT and effector domains, with a characteristic overall structure that arose in fishes from a fusion of the NLR domains with a domain used for immune recognition, the B30.2 domain. The majority of the genes are located on one chromosome arm, interspersed with other large multi-gene families, including a new family encoding proteins with multiple tandem arrays of Zinc fingers. This chromosome arm may be a hot spot for evolutionary change in the zebrafish genome. NLR genes not on this chromosome tend to be located near chromosomal ends.\n\nExtensive duplication, loss of genes and domains, exon shuffling and gene conversion acting differentially on the NACHT and B30.2 domains have shaped the family. Its four groups, which are conserved across the fishes, are homogenised within each group by gene conversion, while the B30.2 domain is subject to gene conversion across the groups. Evidence of positive selection on diversifying mutations in the B30.2 domain, probably driven by pathogen interactions, indicates that this domain rather than the LRRs acts as a recognition domain. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system.

Genomics

Structure and evolutionary history of a large family of NLR proteins in the zebrafish

NACHT- and Leucine-Rich-Repeat-containing domain (NLR) proteins act as cytoplasmic sensors for pathogen- and danger-associated molecular patterns and are found throughout the plant and animal kingdoms. In addition to having a small set of conserved NLRs, the genomes in some animal lineages contain massive expansions of this gene family. One of these arose in fishes, after the creation of a gene fusion that combined the core NLR domains with another domain used for immune recognition, the PRY/SPRY or B30.2 domain. We have analysed the expanded NLR gene family in zebrafish, which contains 368 genes, and studied its evolutionary history. The encoded proteins share a defining overall structure, but individual domains show different evolutionary trajectories. Our results suggest gene conversion homogenizes NACHT and B30.2 domain sequences among different gene subfamilies, however, the functional implications of its action remains unclear. The majority of the genes are located on the long arm of chromosome 4, interspersed with several other large multi-gene families, including a new family encoding proteins with multiple tandem arrays of Zinc fingers. This suggests that chromosome 4 may be a hotspot for rapid evolutionary change in zebrafish.

Evolutionary Biology