The partition matrix: exploring variable phylogenetic signals along nucleotide sequence alignments

The partition matrix is a graphical tool for comparative analysis of nucleotide sequences following alignment. It is particularly useful for investigating the divergent phylogenies of sequence regions undergoing reticulate evolution. A partition matrix is generated by determining the consistency of the parsimoniously informative sites in a set of aligned sequences with the binary partitions inferred from the sequences. Since the linear order of sites is maintained, the matrix can be used to assess whether the distribution of sites either supporting or conflicting with particular partitions changes along the length of the alignment. The usefulness of the matrix in allowing visual identification of differences in evolutionary history among regions depends on the order in which partitions are shown; several suitable ordering schemes are proposed. We demonstrate the use of the partition matrix in interpreting the evolution of the pseudoautosomal boundary region on the sex chromosome of catarrhine primates. Its routine use should help to avoid attempts to derive single phylogenies from sequences whose evolution has been reticulate and to identify the gene conversion or recombination events underlying the reticulation. The method is relatively fast. It is exploratory, and it can form the basis for more formal analysis, which we discuss.      

Positive selection and sequence rearrangements generate extensive polymorphism in the gamete recognition protein bindin

Bindin is a gamete recognition protein of sea urchins that mediates species-specific attachment of sperm to an egg-surface receptor during fertilization. Sequences of bindin from closely related urchins show fixed species-specific differences. Within species, highly polymorphic bindin alleles result from point substitution, insertion/deletion, and recombination. Since speciation, positive selection favoring allelic variants has generated diversity in bindin polypeptides. Intraspecific bindin variation can be tolerated by the egg receptor, which suggests functional parallels between this system and other flexible recognition systems, including immune recognition. These results show that polymorphism in mate recognition loci required for rapid evolution of sexual isolation can arise within natural populations.      

CONTIG EXPLORER: Interactive Marker-Content Map Assembly

In STS-content mapping of a region, multiple optimal or near-optimal putative orders of markers exist. Determining which of the markers in this region can be placed reliably on the physical map of the chromosome and which markers lack sufficient evidence to be placed requires software that facilitates exploratory sensitivity analysis and interactive reassembly with different subsets of the input data and that also assists the evaluation of any arbitrary (user-specified) marker order. We describe CONTIG EXPLORER, a package for interactive assembly of STS-content maps that provides the user with various ways of performing such analyses, thereby facilitating the design of laboratory experiments aimed at reducing ambiguity in STS order. We then compare the output of CONTIG EXPLORER with two other assembly programs, SEGMAP and CONTIGMAKER, for a region of chromosome 12p between 21 and 38 cM on the sex-averaged CEPH/Généthon linkage map.     

eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling

Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments.     

Modelling Vesicular Release at Hippocampal Synapses

We study local calcium dynamics leading to a vesicle fusion in a stochastic, and spatially explicit, biophysical model of the CA3-CA1 presynaptic bouton. The kinetic model for vesicle release has two calcium sensors, a sensor for fast synchronous release that lasts a few tens of milliseconds and a separate sensor for slow asynchronous release that lasts a few hundred milliseconds. A wide range of data can be accounted for consistently only when a refractory period lasting a few milliseconds between releases is included. The inclusion of a second sensor for asynchronous release with a slow unbinding site, and thereby a long memory, affects short-term plasticity by facilitating release. Our simulations also reveal a third time scale of vesicle release that is correlated with the stimulus and is distinct from the fast and the slow releases. In these detailed Monte Carlo simulations all three time scales of vesicle release are insensitive to the spatial details of the synaptic ultrastructure. Furthermore, our simulations allow us to identify features of synaptic transmission that are universal and those that are modulated by structure.