9,437 research outputs found
Frustration in Biomolecules
Biomolecules are the prime information processing elements of living matter.
Most of these inanimate systems are polymers that compute their structures and
dynamics using as input seemingly random character strings of their sequence,
following which they coalesce and perform integrated cellular functions. In
large computational systems with a finite interaction-codes, the appearance of
conflicting goals is inevitable. Simple conflicting forces can lead to quite
complex structures and behaviors, leading to the concept of "frustration" in
condensed matter. We present here some basic ideas about frustration in
biomolecules and how the frustration concept leads to a better appreciation of
many aspects of the architecture of biomolecules, and how structure connects to
function. These ideas are simultaneously both seductively simple and perilously
subtle to grasp completely. The energy landscape theory of protein folding
provides a framework for quantifying frustration in large systems and has been
implemented at many levels of description. We first review the notion of
frustration from the areas of abstract logic and its uses in simple condensed
matter systems. We discuss then how the frustration concept applies
specifically to heteropolymers, testing folding landscape theory in computer
simulations of protein models and in experimentally accessible systems.
Studying the aspects of frustration averaged over many proteins provides ways
to infer energy functions useful for reliable structure prediction. We discuss
how frustration affects folding, how a large part of the biological functions
of proteins are related to subtle local frustration effects and how frustration
influences the appearance of metastable states, the nature of binding
processes, catalysis and allosteric transitions. We hope to illustrate how
Frustration is a fundamental concept in relating function to structural
biology.Comment: 97 pages, 30 figure
The Mathematics of Phylogenomics
The grand challenges in biology today are being shaped by powerful
high-throughput technologies that have revealed the genomes of many organisms,
global expression patterns of genes and detailed information about variation
within populations. We are therefore able to ask, for the first time,
fundamental questions about the evolution of genomes, the structure of genes
and their regulation, and the connections between genotypes and phenotypes of
individuals. The answers to these questions are all predicated on progress in a
variety of computational, statistical, and mathematical fields.
The rapid growth in the characterization of genomes has led to the
advancement of a new discipline called Phylogenomics. This discipline results
from the combination of two major fields in the life sciences: Genomics, i.e.,
the study of the function and structure of genes and genomes; and Molecular
Phylogenetics, i.e., the study of the hierarchical evolutionary relationships
among organisms and their genomes. The objective of this article is to offer
mathematicians a first introduction to this emerging field, and to discuss
specific mathematical problems and developments arising from phylogenomics.Comment: 41 pages, 4 figure
Strong Purifying Selection at Synonymous Sites in D. melanogaster
Synonymous sites are generally assumed to be subject to weak selective
constraint. For this reason, they are often neglected as a possible source of
important functional variation. We use site frequency spectra from deep
population sequencing data to show that, contrary to this expectation, 22% of
four-fold synonymous (4D) sites in D. melanogaster evolve under very strong
selective constraint while few, if any, appear to be under weak constraint.
Linking polymorphism with divergence data, we further find that the fraction of
synonymous sites exposed to strong purifying selection is higher for those
positions that show slower evolution on the Drosophila phylogeny. The function
underlying the inferred strong constraint appears to be separate from splicing
enhancers, nucleosome positioning, and the translational optimization
generating canonical codon bias. The fraction of synonymous sites under strong
constraint within a gene correlates well with gene expression, particularly in
the mid-late embryo, pupae, and adult developmental stages. Genes enriched in
strongly constrained synonymous sites tend to be particularly functionally
important and are often involved in key developmental pathways. Given that the
observed widespread constraint acting on synonymous sites is likely not limited
to Drosophila, the role of synonymous sites in genetic disease and adaptation
should be reevaluated
Patterns of Inter-Chromosomal Gene Conversion on the Male-Specific Region of the Human Y Chromosome
The male-specific region of the human Y chromosome (MSY) is characterized by the lack of meiotic recombination and it has long been considered an evolutionary independent region of the human genome. In recent years, however, the idea that human MSY did not have an independent evolutionary history begun to emerge with the discovery that inter-chromosomal gene conversion (ICGC) can modulate the genetic diversity of some portions of this genomic region. Despite the study of the dynamics of this molecular mechanism in humans is still in its infancy, some peculiar features and consequences of it can be summarized. The main effect of ICGC is to increase the allelic diversity of MSY by generating a significant excess of clustered single nucleotide polymorphisms (SNPs) (defined as groups of two or more SNPs occurring in close proximity and on the same branch of the Y phylogeny). On the human MSY, 13 inter-chromosomal gene conversion hotspots (GCHs) have been identified so far, involving donor sequences mainly from the X-chromosome and, to a lesser extent, from autosomes. Most of the GCHs are evolutionary conserved and overlap with regions involved in aberrant X-Y crossing-over. This review mainly focuses on the dynamics and the current knowledge concerning the recombinational landscape of the human MSY in the form of ICGC, on how this molecular mechanism may influence the evolution of the MSY, and on how it could affect the information enclosed within a genomic region which, until recently, appeared to be an evolutionary independent unit
The Triplet Genetic Code had a Doublet Predecessor
Information theoretic analysis of genetic languages indicates that the
naturally occurring 20 amino acids and the triplet genetic code arose by
duplication of 10 amino acids of class-II and a doublet genetic code having
codons NNY and anticodons . Evidence for this scenario
is presented based on the properties of aminoacyl-tRNA synthetases, amino acids
and nucleotide bases.Comment: 10 pages (v2) Expanded to include additional features, including
likely relation to the operational code of the tRNA-acceptor stem. Version to
be published in Journal of Theoretical Biolog
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