Pseudogene

About: Pseudogene is a research topic. Over the lifetime, 5528 publications have been published within this topic receiving 336634 citations. The topic is also known as: Ψ & pseudogenes.

Complete genome sequence of Rickettsia typhi and comparison with sequences of other rickettsiae.

Abstract: Rickettsia typhi, the causative agent of murine typhus, is an obligate intracellular bacterium with a life cycle involving both vertebrate and invertebrate hosts. Here we present the complete genome sequence of R. typhi (1,111,496 bp) and compare it to the two published rickettsial genome sequences: R. prowazekii and R. conorii. We identified 877 genes in R. typhi encoding 3 rRNAs, 33 tRNAs, 3 noncoding RNAs, and 838 proteins, 3 of which are frameshifts. In addition, we discovered more than 40 pseudogenes, including the entire cytochrome c oxidase system. The three rickettsial genomes share 775 genes: 23 are found only in R. prowazekii and R. typhi, 15 are found only in R. conorii and R. typhi, and 24 are unique to R. typhi. Although most of the genes are colinear, there is a 35-kb inversion in gene order, which is close to the replication terminus, in R. typhi, compared to R. prowazekii and R. conorii. In addition, we found a 124-kb R. typhi-specific inversion, starting 19 kb from the origin of replication, compared to R. prowazekii and R. conorii. Inversions in this region are also seen in the unpublished genome sequences of R. sibirica and R. rickettsii, indicating that this region is a hot spot for rearrangements. Genome comparisons also revealed a 12-kb insertion in the R. prowazekii genome, relative to R. typhi and R. conorii, which appears to have occurred after the typhus (R. prowazekii and R. typhi) and spotted fever (R. conorii) groups diverged. The three-way comparison allowed further in silico analysis of the SpoT split genes, leading us to propose that the stringent response system is still functional in these rickettsiae.

Characterization of frequent deletions causing steroid 21-hydroxylase deficiency

Abstract: Steroid 21-hydroxylase deficiency is caused by mutations in the CYP21B gene. This gene and a highly homologous pseudogene, CYP21A, alternate with the C4A and C4B genes encoding the fourth component of complement. Classical deficiency alleles are frequently caused by deletions of CYP21B or by gene conversions that transfer deleterious mutations from the CYP21A pseudogene to CYP21B. Gene conversions involving restriction enzyme sites that distinguish CYP21A [e.g., 3.2-kilobase (kb) Taq I fragment] and CYP21B (3.7-kb Taq I fragment) might be confused with actual deletions of CYP21B. To determine the incidence of this type of gene conversion, 15 chromosomes (in 13 families) with absent 3.7-kb Taq I fragments were studied. When hybridized with a 21-hydroxylase probe, all of these chromosomes were associated with absent 2.9-kb Kpn I fragments, 14 of 15 were associated with absent 2.4-kb Bgl II/EcoRI fragments, and 13 of 15 were associated with absent 10-kb Bgl II/EcoRI and 12-kb EcoRI fragments. Thirteen of 15 chromsomes had absent 6.0- or 5.4-kb Taq I fragments when hybridized with a C4 probe. Thus, 2 of 15 chromosomes do not carry deletions and may represent gene conversions; 13 of 15 chromosomes studied have a deletion of approximately equal to 30 kb, leaving behind the C4A gene and a single CYP21A-like gene. Hybridization with specific oligonucleotide probes showed that in all 13 cases this remaining CYP21 gene carried an 8-base-pair deletion, typical of CYP21A, that prevents synthesis of a functional protein. Thus, gene conversions are rarely confused with deletions as a cause of 21-hydroxylase deficiency.

Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes.

Abstract: Three genes closely related to the D1 dopamine receptor were identified in the human genome. One of the genes lacks introns and encodes a functional human dopamine receptor, D5, whose deduced amino acid sequence is 49% identical to that of the human D1 receptor. Compared with the human D1 dopamine receptor, the D5 receptor displayed a higher affinity for dopamine and was able to stimulate a biphasic rather than a monophasic intracellular accumulation of cAMP. Neither of the other two genes was able to direct the synthesis of a receptor. Nucleotide sequence analysis revealed that these two genes are 98% identical to each other and 95% identical to the D5 sequence. Relative to the D5 sequence, both contain insertions and deletions that result in several in-frame termination codons. Premature termination of translation is the most likely explanation for the failure of these genes to produce receptors in COS-7 and 293 cells even though their messages are transcribed. We conclude that the two are pseudogenes. Blot hybridization experiments performed on rat genomic DNA suggest that there is one D5 gene in this species and that the pseudogenes may be the result of a relatively recent evolutionary event.

Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates.

Abstract: The numbers of functional olfactory receptor (OR) genes in humans and mice are about 400 and 1,000 respectively. In both humans and mice, these genes exist as genomic clusters and are scattered over almost all chromosomes. The difference in the number of genes between the two species is apparently caused by massive inactivation of OR genes in the human lineage and a substantial increase of OR genes in the mouse lineage after the human–mouse divergence. Compared with mammals, fishes have a much smaller number of OR genes. However, the OR gene family in fishes is much more divergent than that in mammals. Fishes have many different groups of genes that are absent in mammals, suggesting that the mammalian OR gene family is characterized by the loss of many group genes that existed in the ancestor of vertebrates and the subsequent expansion of specific groups of genes. Therefore, this gene family apparently changed dynamically depending on the evolutionary lineage and evolved under the birth-and-death model of evolution. Study of the evolutionary changes of two gene families for vomeronasal receptors and two gene families for taste receptors, which are structurally similar, but remotely related to OR genes, showed that some of the gene families evolved in the same fashion as the OR gene family. It appears that the number and types of genes in chemosensory receptor gene families have evolved in response to environmental needs, but they are also affected by fortuitous factors.

Ecological adaptation determines functional mammalian olfactory subgenomes

Abstract: The ability to smell is governed by the largest gene family in mammalian genomes, the olfactory receptor (OR) genes. Although these genes are well annotated in the finished human and mouse genomes, we still do not understand which receptors bind specific odorants or how they fully function. Previous comparative studies have been taxonomically limited and mostly focused on the percentage of OR pseudogenes within species. No study has investigated the adaptive changes of functional OR gene families across phylogenetically and ecologically diverse mammals. To determine the extent to which OR gene repertoires have been influenced by habitat, sensory specialization, and other ecological traits, to better understand the functional importance of specific OR gene families and thus the odorants they bind, we compared the functional OR gene repertoires from 50 mammalian genomes. We amplified more than 2000 OR genes in aquatic, semi-aquatic, and flying mammals and coupled these data with 48,000 OR genes from mostly terrestrial mammals, extracted from genomic projects. Phylogenomic, Bayesian assignment, and principle component analyses partitioned species by ecotype (aquatic, semi-aquatic, terrestrial, flying) rather than phylogenetic relatedness, and identified OR families important for each habitat. Functional OR gene repertoires were reduced independently in the multiple origins of aquatic mammals and were significantly divergent in bats. We reject recent neutralist views of olfactory subgenome evolution and correlate specific OR gene families with physiological requirements, a preliminary step toward unraveling the relationship between specific odors and respective OR gene families.