Biomedical subjects

M B Gerstein

Publications and source records attributed to M B Gerstein.

3 recordsLinked to original sources

PubMed2001

Digging for dead genes: an analysis of the characteristics of the pseudogene population in the Caenorhabditis elegans genome.

Pseudogenes are non-functioning copies of genes in genomic DNA, which may either result from reverse transcription from an mRNA transcript (processed pseudogenes) or from gene duplication and subsequent disablement (non-processed pseudogenes). As pseudogenes are apparently 'dead', they usually have a variety of obvious disablements (e.g., insertions, deletions, frameshifts and truncations) relative to their functioning homologs. We have derived an initial estimate of the size, distribution and characteristics of the pseudogene population in the Caenorhabditis elegans genome, performing a survey in 'molecular archaeology'. Corresponding to the 18 576 annotated proteins in the worm (i.e., in Wormpep18), we have found an estimated total of 2168 pseudogenes, about one for every eight genes. Few of these appear to be processed. Details of our pseudogene assignments are available from http://bioinfo.mbb.yale.edu/genome/worm/pseudogene. The population of pseudogenes differs significantly from that of genes in a number of respects: (i) pseudogenes are distributed unevenly across the genome relative to genes, with a disproportionate number on chromosome IV; (ii) the density of pseudogenes is higher on the arms of the chromosomes; (iii) the amino acid composition of pseudogenes is midway between that of genes and (translations of) random intergenic DNA, with enrichment of Phe, Ile, Leu and Lys, and depletion of Asp, Ala, Glu and Gly relative to the worm proteome; and (iv) the most common protein folds and families differ somewhat between genes and pseudogenes-whereas the most common fold found in the worm proteome is the immunoglobulin fold and the most common 'pseudofold' is the C-type lectin. In addition, the size of a gene family bears little overall relationship to the size of its corresponding pseudogene complement, indicating a highly dynamic genome. There are in fact a number of families associated with large populations of pseudogenes. For example, one family of seven-transmembrane receptors (represented by gene B0334.7) has one pseudogene for every four genes, and another uncharacterized family (represented by gene B0403.1) is approximately two-thirds pseudogenic. Furthermore, over a hundred apparent pseudogenic fragments do not have any obvious homologs in the worm.

Amino Acid Sequence↗

PubMed2001

Global perspectives on proteins: comparing genomes in terms of folds, pathways and beyond.

The sequencing of complete genomes provides us with a global view of all the proteins in an organism. Proteomic analysis can be done on a purely sequence-based level, with a focus on finding homologues and grouping them into families and clusters of orthologs. However, incorporating protein structure into this analysis provides valuable simplification; it allows one to collect together very distantly related sequences, thus condensing the proteome into a minimal number of 'parts.' We describe issues related to surveying proteomes in terms of structural parts, including methods for fold assignment and formats for comparisons (eg top-10 lists and whole-genome trees), and show how biases in the databases and in sampling can affect these surveys. We illustrate our main points through a case study on the unique protein properties evident in many thermophile genomes (eg more salt bridges). Finally, we discuss metabolic pathways as an even greater simplification of genomes. In comparison to folds these allow the organization of many more genes into coherent systems, yet can nevertheless be understood in many of the same terms.

Animals↗

PubMed1995

Methods for displaying macromolecular structural uncertainty: application to the globins.

Most molecular graphics programs ignore any uncertainty in the atomic coordinates being displayed. Structures are displayed in terms of perfect points, spheres, and lines with no uncertainty. However, all experimental methods for defining structures, and many methods for predicting and comparing structures, associate uncertainties with each atomic coordinate. We have developed graphical representations that highlight these uncertainties. These representations are encapsulated in a new interactive display program, PROTEAND. PROTEAND represents structural uncertainty in three ways: (1) The traditional way: The program shows a collection of structures as superposed and overlapped stick-figure models. (2) Ellipsoids: At each atom position, the program shows an ellipsoid derived from a three-dimensional Gaussian model of uncertainty. This probabilistic model provides additional information about the relationship between atoms that can be displayed as a correlation matrix. (3) Rigid-body volumes: Using clouds of dots, the program can show the range of rigid-body motion of selected substructures, such as individual alpha helices. We illustrate the utility of these display modalities by the applying PROTEAND to the globin family of proteins, and show that certain types of structural variation are best illustrated with different methods of display.

Animals↗