Remnant of Unrelated Amniote Sex Chromosomal Linkage Sharing on the Same Chromosome in House Gecko Lizards, Providing a Better Understanding of the Ancestral Super-Sex Chromosome

Comparative chromosome maps investigating sex chromosomal linkage groups in amniotes and microsatellite repeat motifs of a male house gecko lizard (Hemidactylus frenatus, HFR) and a flat-tailed house gecko lizard (H. platyurus, HPL) of unknown sex were examined using 75 bacterial artificial chromosomes (BACs) from chicken and zebra finch genomes. No massive accumulations of microsatellite repeat motifs were found in either of the gecko lizards, but 10 out of 13 BACs mapped on HPL chromosomes were associated with other amniote sex chromosomes. Hybridization of the same BACs onto multiple different chromosome pairs suggested transitions to sex chromosomes across amniotes. No BAC hybridization signals were found on HFR chromosomes. However, HFR diverged from HPL about 30 million years ago, possibly due to intrachromosomal rearrangements occurring in the HFR lineage. By contrast, heterochromatin likely reshuffled patterns between HPL and HFR, as observed from C-positive heterochromatin distribution. Six out of ten BACs showed partial homology with squamate reptile chromosome 2 (SR2) and snake Z and/or W sex chromosomes. The gecko lizard showed shared unrelated sex chromosomal linkages—the remnants of a super-sex chromosome. A large ancestral super-sex chromosome showed a correlation between SR2 and snake W sex chromosomes.

Inhibitory Proteins Block Substrate Access to the Active Site of Bacillus subtilis Intramembrane Metalloprotease SpoIVFB

Intramembrane proteases of diverse signaling pathways use membrane-embedded active sites to cleave membrane-associated substrates. Interactions of intramembrane metalloproteases with modulators are poorly understood. Inhibition of Bacillus subtilis intramembrane metalloprotease SpoIVFB requires BofA and SpoIVFA, which transiently prevent cleavage of Pro-σK during endosporulation. Three conserved BofA residues (N48, N61, T64) in or near predicted transmembrane segment (TMS) 2 were found to be required for SpoIVFB inhibition. Disulfide cross-linking indicated that BofA TMS2 occupies the SpoIVFB active site region. BofA and SpoIVFA neither prevented SpoIVFB from interacting with Pro-σK in co-purification assays nor interfered with cross-linking between the C-terminal regions of Pro-σK and SpoIVFB. However, BofA and SpoIVFA did interfere with cross-linking between the N-terminal Proregion of Pro-σK and the SpoIVFB active site region and interdomain linker. A BofA variant lacking predicted TMS1, in combination with SpoIVFA, was less effective at interfering with some of the cross-links and slightly less effective at inhibiting cleavage of Pro-σK by SpoIVFB. A structural model was built of SpoIVFB in complex with BofA and parts of SpoIVFA and Pro-σK, using partial homology and constraints from cross-linking and co-evolutionary analyses. The model predicts that N48 in BofA TMS2 interacts with T64 (and possibly N61) of BofA to stabilize a membrane-embedded C-terminal region. SpoIVFA is predicted to bridge the BofA C-terminal region and SpoIVFB. Thus, the two inhibitory proteins block access of the Pro-σK N-terminal region to the SpoIVFB active site region. Our findings may inform efforts to develop selective inhibitors of intramembrane metalloproteases.

Gene Homologies Identified between Trypanosoma cruzi Antigen 36 and Mammalian TRIM21 Genes Using Bioinformatics Analysis

Background We previously reported that a Human Ro52 gene sequence (TRIM21) produced a significant stretch of protein sequence homologous to T. cruzi Antigen 36 (Ag 36) protein sequence, when Ag 36 was translated in the second reading frame. Comparison of their respective DNA sequences demonstrated a 114 nucleotide region of both genes having ~ 70 percent partial homology. After Ro52 was shown to be an E3 Ubiquitin dependent Type I ligase for transcription factors for Interferon genes, we proposed that the Ag 36 gene, which contains a repetitive motif within it, may function to repress Ro52 in the human heart through RNA interference, or other unknown mechanism, giving rise to autoimmunity found in Chronic Chagas Cardiomyopathy (CCC). Results To test that hypothesis, we compared various mammalian TRIM genes to the T. cruzi Ag 36 DNA sequence using the Needleman-Wunsch algorithm in the http:\\usegalaxy.eu bioinformatics tool base. In addition to human and chimpanzee, TRIM21 comparable gene regions from canine, shrew, ferret, bat, feline, and armadillo, and aardvark showed homology to the gene for Ag 36 ranging from 68 to 30 percent. However, mouse and eight other mammalian species showed no significant homology. Since mice have been shown to have severe cardiac cardiomyopathy after infection, but their TRIM21 was not homologous to Ag 36 in this study, we conclude that the gene homology has no causative link to CCC. Conclusions In addition to human TRIM21, eight mammalian species showed partial gene homology to T. cruzi Ag 36, and some of these have been demonstrated to have CCC. However, rats and mice TRIM21 showed no partial homology to Ag 36. Since these species have been demonstrated to have CCC, the partial gene homology between Ag36 and TRIM 21 may not be causative or associated with CCC, as was originally hypothesized.

Gene Homologies Identified between Trypanosoma cruzi Antigen 36 and Mammalian TRIM21 Genes Using Bioinformatics Analysis

Background: We previously reported that a Human Ro52 gene sequence (TRIM21) produced a significant stretch of protein sequence homologous to T. cruzi Antigen 36 (Ag 36) protein sequence, when Ag 36 was translated in the second reading frame. Comparison of their respective DNA sequences demonstrated a 114 nucleotide region of both genes having ~70 percent partial homology. After Ro52 was shown to be an E3 Ubiquitin dependent Type I ligase for transcription factors for Interferon genes, we proposed that the Ag 36 gene, which contains a repetitive motif within it, may function to repress Ro52 in the human heart through RNA interference, or other unknown mechanism, giving rise to autoimmunity found in Chronic Chagas Cardiomyopathy (CCC).Results: To test that hypothesis, we compared various mammalian TRIM genes to the T. cruzi Ag 36 DNA sequence using the Needleman-Wunsch algorithm in the http:\\usegalaxy.eu bioinformatics tool base. In addition to human and chimpanzee, TRIM21 comparable gene regions from canine, shrew, ferret, bat, feline, and armadillo, and aardvark showed homology to the gene for Ag 36 ranging from 68 to 30 percent. However, mouse and eight other mammalian species showed no significant homology. Since mice have been shown to have severe cardiac cardiomyopathy after infection, but their TRIM21 was not homologous to Ag 36 in this study, we conclude that the gene homology has no causative link to CCC.Conclusions: In addition to human TRIM21, eight mammalian species showed partial gene homology to T. cruzi Ag 36, and some of these have been demonstrated to have CCC. However, rats and mice TRIM21 showed no partial homology to Ag 36. Since these species have been demonstrated to have CCC, the partial gene homology between Ag36 and TRIM 21 may not be causative or associated with CCC, as was originally hypothesized.

Ab Initio Construction and Evolutionary Analysis of Protein-Coding Gene Families with Partially Homologous Relationships: Closely Related Drosophila Genomes as a Case Study

How have genes evolved within a well-known genome phylogeny? Many protein-coding genes should have evolved as a whole at the gene level, and some should have evolved partly through fragments at the subgene level. To comprehensively explore such complex homologous relationships and better understand gene family evolution, here, with de novo-identified modules, the subgene units which could consecutively cover proteins within a set of closely related species, we applied a new phylogeny-based approach that considers evolutionary models with partial homology to classify all protein-coding genes in nine Drosophila genomes. Compared with two other popular methods for gene family construction, our approach improved practical gene family classifications with a more reasonable view of homology and provided a much more complete landscape of gene family evolution at the gene and subgene levels. In the case study, we found that most expanded gene families might have evolved mainly through module rearrangements rather than gene duplications and mainly generated single-module genes through partial gene duplication, suggesting that there might be pervasive subgene rearrangement in the evolution of protein-coding gene families. The use of a phylogeny-based approach with partial homology to classify and analyze protein-coding gene families may provide us with a more comprehensive landscape depicting how genes evolve within a well-known genome phylogeny.

Cell-to-Cell Variation in Gene Expression for Cultured Human Cells Is Controlled in Trans by Diverse Genes: Implications for the Pathobiology of Aging

Cell-to-cell variation in gene expression increases among homologous cells within multiple tissues during aging. We call this phenomenon variegated gene expression (VGE). Long, healthy life requires robust and coordinated gene expression. We posit that nature may have evolved VGE as a bet-hedging mechanism to protect reproductively active populations. The price we may pay is accelerated aging. That hypothesis will require the demonstration that genetic loci are capable of modulating degrees of VGE. While loci controlling VGE in yeast and genes controlling interindividual variation in gene expression in Caenorhabditis elegans have been identified, there has been no compelling evidence for the role of specific genetic loci in modulations of VGE of specific targets in humans. With the assistance of a core facility, we used a customized library of siRNA constructs to screen 1,195 human genes to identify loci contributing to the control of VGE of a gene with relevance to the biology of aging. We identified approximately 50 loci controlling VGE of the prolongevity gene, SIRT1. Because of its partial homology to FOXO3A, a variant of which is enriched in centenarians, our laboratory independently confirmed that the knockdown of FOXF2 greatly diminished VGE of SIRT1 but had little impact upon the VGE of WRN. While the role of these VGE-altering genes on aging in vivo remains to be determined, we hypothesize that some of these genes can be targeted to increase functionality during aging.

Formation of the L1Hs retroelement in the intron of the MGMT gene of hominoidea

Aim. Analyze the formation of a human-specific L1Hs element in the intron 3 of the MGMT gene on an example of a hominid. Methods. The results of the search and identification of mobile genetic elements were performed using the CENSOR program. The homology between nucleotide sequences was determined by BLAST 2.6.1. Results. The components of the cluster, where the L1Hs element in the human being was formed, are fragments of the L1PA6 element, which are common in the monkeys of the Old and New World. In the gibbon, among the L1 element groups, there are representatives of older subfamilies (L1PB, L1MC, L1MD and L1ME), and the partial homology to the L1Hs of the element is predominantly of elements of groups that have arisen in the mammalian genomes. Conclusions. Formation of a human-specific L1Hs element occurred during the evolution of Hominoidea in parallel with the formation of the cluster structure of MGE in humans from different subfamilies of LINE1-elements whose component components, obviously, also involved in the formation of the L1Hs element. Keywords: Hominoidea, MGMT gene, intron 3, human-specific L1Hs element.

Eukaryote Genes Are More Likely than Prokaryote Genes to Be Composites

The formation of new genes by combining parts of existing genes is an important evolutionary process. Remodelled genes, which we call composites, have been investigated in many species, however, their distribution across all of life is still unknown. We set out to examine the extent to which genomes from cells and mobile genetic elements contain composite genes. We identify composite genes as those that show partial homology to at least two unrelated component genes. In order to identify composite and component genes, we constructed sequence similarity networks (SSNs) of more than one million genes from all three domains of life, as well as viruses and plasmids. We identified non-transitive triplets of nodes in this network and explored the homology relationships in these triplets to see if the middle nodes were indeed composite genes. In total, we identified 221,043 (18.57%) composites genes, which were distributed across all genomic and functional categories. In particular, the presence of composite genes is statistically more likely in eukaryotes than prokaryotes.

Regulated Endocrine-Specific Protein-18, an Emerging Endocrine Protein in Physiology: A Literature Review

Regulated endocrine-specific protein-18 (RESP18), a novel 18-kDa protein, was first identified in neuroendocrine tissue. Subsequent studies showed that Resp18 is expressed in the adrenal medulla, brain, pancreas, pituitary, retina, stomach, superior cervical ganglion, testis, and thyroid and also circulates in the plasma. Resp18 has partial homology with the islet cell antigen 512, also known as protein tyrosine phosphatase, receptor type N (PTPRN), but does not have phosphatase activity. Resp18 might serve as an intracellular signal; however, its function is unclear. It is regulated by dopamine, glucocorticoids, and insulin. We recently reported that the targeted disruption of the Resp18 locus in Dahl salt-sensitive rats increased their blood pressure and caused renal injury. The aim of the present review was to provide a comprehensive summary of the reported data currently available, especially the expression and proposed organ-specific function of Resp18.