Biomedical subjects

Felix Friedberg

Publications and source records attributed to Felix Friedberg.

5 recordsLinked to original sources

PubMed2006

Centrin isoforms in mammals. Relation to calmodulin.

In mammals, three calmodulin (CaM) genes code for 100% identical proteins. In these species, four centrin (Cetn) genes have been reported to exist. They are examined in this paper. While the gene for Cetn 1 contains no introns and appears to be derived from Cetn 2 by retroposition, a gene product for Cetn 1 is expressed. Cetn 2, 3, and 4 represent bona fide genes. The major difference between the members of the CaM and the Cetn subfamilies is the presence (usually) in Cetn of an approximately 23 amino acids long (but occasionally much longer) protruding amino acid end. In all members of these two subgroups, four EF hand motifs (in this paper taken as loops containing 12 amino acids) are separated by 24, 25 and 24 amino acids (each a helix-loop-helix) positioned between motifs 1and 2, 2 and 3, and 3 and 4, respectively. This rule applies not only to CaM and Cetn in mammals but also to these two subfamilies in simpler eukaryotes such as Saccharomyces cerevisiae and Giardia lamblia. The various mRNA products can be identified most readily by their characteristic 3' UTRs. While CaM is an ancient molecule that is expressed in all cells and is ubiquitous within these cells and interacts therein with almost 100 different proteins, many of which display the IQ or related binding motifs, the distribution and function of Cetn (an equally ancient molecule) is restricted mostly to basal bodies (e.g. in rods of the retina), axonemes, flagella, cilia and centrosomes. Are these two subclasses of calcium carriers (each molecule possessing four EF hands which possibly interact with different association constants)-if they are both present within a cell-randomly chosen for their service to the specific proteins with which they interact?

Amino Acid Sequence↗

PubMed2005

Calmodulin genes in zebrafish (revisited).

Calmodulin (CaM), a ubiquitous protein, ancestral in early eukaryotes, regulates a large number of physiologically important functions by activating other proteins, some of them enzymes, usually in response to changes in the local concentration of calcium ions. Invertebrates possess one gene that codes for CaM. Among vertebrates, mammals display three genes that code for a 100% identical CaM molecule, while for zebra fishes etc., a non-mammalian vertebrate, we reported earlier the existence of four such genes. The number of multiple genes coding for a 100% identical CaM molecule present in the zebra fish genome, however, is corrected here, from the four, as previously suggested, to six (alpha, alpha2, beta, beta2, gamma and gamma 2). Identification of each of these genes is readily achieved upon examination of the characteristic 5' and 3' UTRs within their respective mRNAs even though we do not know at present what role these UTRs might play. A scanning of the 3' UTRs for short homology elements among the six genes (and a comparison with the human type I, II, and III CaM 3' UTRs) also suggests that duplication processes for three genes resulted in the formation of six such genes. As they become available, the promoter regions for these six genes should be scanned for possible identification of putative regulatory elements if we are to understand the need for the uniquely rigid evolutionary maintenance of these six genes. A comparison of the promoter regions for the beta and beta 2 genes is presented in this paper. A few common short homologous elements appear to be retained in these generally highly variant two regions, but conclusions about differential expression controls must be delayed until the promoter regions for all the other CaM genes have been examined.

Animals↗

PubMed2005

Parvalbumin isoforms in zebrafish.

By using an analysis of existing genomic information it is concluded that in zebrafish nine genes encode parvalbumin (PV). These genes possess introns that differ in size and show nucleotide variability but they contain the same number of exons, and for each corresponding exon, the number of nucleotides therein are identical in all the paralogs. This rule also applies to the multiple PV genes of other species e.g. mammals. Each of these genes displays, however, characteristic 5' and 3' UTRs which appear highly conserved between closely related species (so that orthologs among these species can be readily identified) but which show larger numbers of mutations between species that are more distant in evolution. A tree is presented which suggests that the traditional classification of PVs as alpha or beta (based mainly on charge of the protein molecule) is not sustainable. Numbers 1-9 are assigned to the various isoforms to facilitate their identification in future studies. A bifurcation of isoforms into 1 and 4; 2 and 3; 6 and 7; 8 and 9 appears to have occurred simultaneously in more recent time, i.e. perhaps approximately 60 mys ago when primates and rodents branched.

Amino Acid Sequence↗

PubMed2002

Age and detection of retroprocessed pseudogenes in murine rodents.

Retroprocessed pseudogenes, calmodulin II (psi1, psi2, and psi3 CALMII), psi alpha-tubulin, pi-glutathione S-transferase (psi pi-GST) from rat, lactic acid dehydrogenase (psi LDH) from mouse, and heat shock protein 60 chaperonin (psi HSP60) from Chinese hamster, were examined for their presence in these species by polymerase chain reaction (PCR). Pseudogenes of these murine rodents were detected by PCR only in those species in which the genes were originally identified, suggesting that the selected pseudogene of one species arose too recently to be detected in the genomes of the other rodent species. The calculated ages of the rodent pseudogenes ranged from 1.7 Myr (psi alpha-tubulin) to 7.5 Myr (psi3 CALMII) when employing a homologous functional gene of the taxon as a reference in the relative rate test with the mouse or rat as the outgroup. Given the high rate of divergence of the genes of rodents relative to other species, selection of an outgroup with similar mutation rates seems warranted. To justify further the conclusion that the selected pseudogenes were indeed retroprocessed after these three taxa diverged, the presence of the pseudogenes in the genome of different rat species was examined. The existence of psi3 CALMII and psi alpha-tubulin pseudogenes of Rattus norvegicus among species belonging to Rattus sensu stricto is evidence for the common ancestry of this group.

Animals↗

PubMed2002

Multiple calmodulin genes in fish.

In mammals, identical calmodulin (CaM) proteins are encoded by three nonallelic genes that differ in their promoter regions and untranslated regions (UTRs). The UTRs of each of these three genes are specific for each gene and are highly conserved. In this study, sequences obtained from the GenBank and EST databases and sequencing were examined for several species of fish to ascertain whether this multi-gene one protein system exhibited in mammals extends to other vertebrates. Three genes in zebrafish (Danio rerio) designated alpha, beta, and gamma were identified. As in mammals, these genes differ in the 3'-UTR region but encode completely identical CaMs. PCR primers spanning the coding and the 3'-UTR regions were designed based on the assembled sequences and used to confirm the presence of each gene in the cDNA library. Other species of fish were also found to contain homologous genes that were closely related as indicated by phylogenetic analysis. The 3'-UTR of the alpha, beta and particularly the gamma CaM gene of fish were not found to be as conserved as the corresponding genes of mammalian species possibly due to the span of evolutionary time. Only a few short elements in the 3'-UTR were observed to be similar in fish and mammals. These short regions of identity are shared primarily between the mammalian CaM II and CaM I and the alpha gene and beta gene of fish, respectively. Thus, the multi-gene one protein system occurs among fish as well as among mammals.

3' Untranslated Regions↗