Simple algorithms for the estimation of the initial number of individuals in commingled skeletal remains

The determination of the number of individuals represented within commingled remains is based on two types of estimators, those assessing the minimum number of individuals and those assessing the most likely number of individuals. Much as the latter produce improved results, they still exhibit significant drawbacks, which are related to the misidentification of the number of pairs between the existing bilateral elements. This article addresses these problems through the use of two computer algorithms. One algorithm produces a number of potential pairs between bilateral elements and the other estimates the number of individuals in a commingled sample by incorporating the percentages of lost and altered bones into the analysis. These algorithms were validated using hypothetical and actual skeletal samples, and are more effective in comparison to any conventional estimators, particularly in cases, where the elements are poorly preserved.     

A slowly evolving host moves first in symbiotic interactions

Symbiotic relationships, both parasitic and mutualistic, are ubiquitous in nature. Understanding how these symbioses evolve, from bacteria and their phages to humans and our gut microflora, is crucial in understanding how life operates. Often, symbioses consist of a slowly evolving host species with each host only interacting with its own subpopulation of symbionts. The Red Queen hypothesis describes coevolutionary relationships as constant arms races with each species rushing to evolve an advantage over the other, suggesting that faster evolution is favored. Here, we use a simple game theoretic model of host-symbiont coevolution that includes population structure to show that if the symbionts evolve much faster than the host, the equilibrium distribution is the same as it would be if it were a sequential game where the host moves first against its symbionts. For the slowly evolving host, this will prove to be advantageous in mutualisms and a handicap in antagonisms. The result follows from rapid symbiont adaptation to its host and is robust to changes in the parameters, even generalizing to continuous and multiplayer games. Our findings provide insight into a wide range of symbiotic phenomena and help to unify the field of coevolutionary theory.     

Genome structure and the benefit of sex

We examine the behavior of sexual and asexual populations in modular multipeaked fitness landscapes and show that sexuals can systematically reach different, higher fitness adaptive peaks than asexuals. Whereas asexuals must move against selection to escape local optima, sexuals reach higher fitness peaks reliably because they create specific genetic variants that "skip over" fitness valleys, moving from peak to peak in the fitness landscape. This occurs because recombination can supply combinations of mutations in functional composites or "modules," that may include individually deleterious mutations. Thus when a beneficial module is substituted for another less-fit module by sexual recombination it provides a genetic variant that would require either several specific simultaneous mutations in an asexual population or a sequence of individual mutations some of which would be selected against. This effect requires modular genomes, such that subsets of strongly epistatic mutations are tightly physically linked. We argue that such a structure is provided simply by virtue of the fact that genomes contain many genes each containing many strongly epistatic nucleotides. We briefly discuss the connections with "building blocks" in the evolutionary computation literature. We conclude that there are conditions in which sexuals can systematically evolve high-fitness genotypes that are essentially unevolvable for asexuals.     

Effect of balancing selection on spatial genetic structure within populations: theoretical investigations on the self-incompatibility locus and empirical studies in Arabidopsis halleri

The effect of selection on patterns of genetic structure within and between populations may be studied by contrasting observed patterns at the genes targeted by selection with those of unlinked neutral marker loci. Local directional selection on target genes will produce stronger population genetic structure than at neutral loci, whereas the reverse is expected for balancing selection. However, theoretical predictions on the intensity of this signal under precise models of balancing selection are still lacking. Using negative frequency-dependent selection acting on self-incompatibility systems in plants as a model of balancing selection, we investigated the effect of such selection on patterns of spatial genetic structure within a continuous population. Using numerical simulations, we tested the effect of the type of self-incompatibility system, the number of alleles at the self-incompatibility locus and the dominance interactions among them, the extent of gene dispersal, and the immigration rate on spatial genetic structure at the selected locus and at unlinked neutral loci. We confirm that frequency-dependent selection is expected to reduce the extent of spatial genetic structure as compared to neutral loci, particularly in situations with low number of alleles at the self-incompatibility locus, high frequency of codominant interactions among alleles, restricted gene dispersal and restricted immigration from outside populations. Hence the signature of selection on spatial genetic structure is expected to vary across species and populations, and we show that empirical data from the literature as well as data reported here on three natural populations of the herb Arabidopsis halleri confirm these theoretical results.     

Conformational plasticity of the calcium‐binding pocket in the Burkholderia glumae lipase: Remodeling induced by mutation of calcium coordinating residues

Most bacterial lipases bind one or more Ca²⁺ atoms at different locations and are a suitable case of study for investigating structural effects related to calcium binding, depletion, or mutation of calcium‐binding sites. Generally Ca²⁺ in microbial lipases can play a crucial role in the stabilization of the whole three‐dimensional structure by mediating long‐range effects. It has been recently demonstrated that calcium binding influences thermal stability of Burkholderia glumae lipase (BGL) through the restriction of conformational plasticity of specific regions. Moreover, calcium depletion results in a highly cooperative protein unfolding, eliciting protein aggregation. To further shed light on molecular mechanisms and structural features connected to calcium binding in microbial lipases, we present a molecular dynamics investigation, based on multiple‐replica approach at different temperatures, of BGL mutants targeting the calcium‐binding site. It turns out that additional acidic residues, which are conserved in other microbial lipases, help in overcoming effects induced by mutation of D241 Ca²⁺‐coordinating residue, upon rearrangements induced in the calcium binding site. © 2010 Wiley Periodicals, Inc. Biopolymers 95: 117–126, 2011.     

Potential of mean force for separation of the repeating units in cellulose and hemicellulose

As a first step toward understanding the energetics of removal of cello-oligomers from the cellulose surface, we have performed umbrella sampling calculations to determine the free energy required for separation of repeating units of cellulose and hemicellulose from each other. Molecular dynamics (MD) simulations were performed for both the stacked and non-stacked arrangements of the cellobiose pair system and the xylobiose pair system. These stacked and non-stacked arrangements were taken as representative systems for the crystalline and amorphous domains in cellulose and hemicellulose. In addition, similar calculations were also carried out to determine the energetics involved in the separation of the cellobiose–xylobiose molecule pair in the non-stacked arrangement. The potential of mean force profiles exhibit a single minimum in all cases and are qualitatively similar. Our results show that the location of the minimum as well as the depth of the well can be correlated with the size of the disaccharide molecules.     

Fibril elongation mechanisms of HET-s prion-forming domain: topological evidence for growth polarity

The prion-forming C-terminal domain of the fungal prion HET-s forms infectious amyloid fibrils at physiological pH. The conformational switch from the nonprion soluble form to the prion fibrillar form is believed to have a functional role, as HET-s in its prion form participates in a recognition process of different fungal strains. On the basis of the knowledge of the high-resolution structure of the prion forming domain HET-s(218-289) in its fibrillar form, we here present a numerical simulation of the fibril growth process, which emphasizes the role of the topological properties of the fibrillar structure. An accurate thermodynamic analysis of the way an intervening HET-s chain is recruited to the tip of the growing fibril suggests that elongation proceeds through a dock and lock mechanism. First, the chain docks onto the fibril by forming the longest β-strands. Then, the re-arrangement in the fibrillar form of all the rest of the molecule takes place. Interestingly, we also predict that one side of the HET-s fibril is more suitable for sustaining its growth with respect to the other. The resulting strong polarity of fibril growth is a consequence of the complex topology of HET-s fibrillar structure, as the central loop of the intervening chain plays a crucially different role in favoring or not the attachment of the C-terminus tail to the fibril, depending on the growth side.     

Mobility in the structure of E.coli recQ helicase upon substrate binding as seen from molecular dynamics simulations

RecQ helicases feature multiple domains in their structure, of which the helicase domain, the RecQ-Ct domain and the HRDC domains are well conserved among the SF2 helicases. The helicase domain and the RecQ-Ct domain constitute the catalytic core of the enzyme. The domain interfaces are the DNA binding sites which display significant conformational changes in our molecular dynamics simulation studies. The preferred conformational states of the DNA bound and unbound forms of RecQ appear to be quite different from each other. DNA binding induces inter-domain flexibility leading to hinge mobility between the domains. The divergence in the dynamics of the two structures is caused by changes in the interactions at the domain interface, which seems to propagate along the whole protein structure. This could be essential in ssDNA binding after strand separation, as well as aiding translocation of the RecQ protein like an inch-worm.     

Structural analysis of zinc-finger (TTK) + [Cu(BPA)]2+ /[Cu(IDB)]2+ + DNA complexes: an investigation by molecular dynamics simulation

In the present study, the molecular dynamics simulation technique is employed to investigate the hydrogen abstraction possibility from sugar of DNA in two designed complexes of copper-based chemical nuclease [Cu(BPA)](2+) bis(2-pyridylmethyl) amine (BPA) or [Cu(IDB)](2+) N,N-bis(2-benzimidazolylmethyl) amine (IDB) bound to the zinc finger protein Tramtrack (TTK). The simulated results show that each of the designed complexes can form a stable conformation within 30 ns of simulation time with the substrate OOH(-) and an 18-base pair (bp) DNA segment and is located in the major groove of the DNA segment. The active terminal O atom of the OOH(-) substrate is found in close proximity to the target C2'H, C3'H, C4'H or C5'H proton of the DNA in TTK + [Cu(BPA)OOH](+) + DNA or TTK + [Cu(IDB)OOH](+) + DNA complex, which is crucial to propose the hydrogen abstraction possibility that is responsible for the DNA cleavage. The positions of copper-based chemical nucleases bound to TTK may substantially influence the hydrogen abstraction possibility. The structures and sizes of ligands in copper-based nucleases are also found to have influence on the order of difficulty of the hydrogen abstraction from the sugars of DNA.