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Showing papers on "Pseudogene published in 1982"


Journal ArticleDOI
28 Oct 1982-Nature
TL;DR: A size polymorphism associated with the processed gene in the population examined is detected, and a region of apparent secondary structure homology between a 5′ flanking region of the functional metallothionein-II gene and that of a mouse metallothsionin-I gene is observed.
Abstract: The complete nucleotide sequence of two of the human metallothionein gene family has been compared. One is a functional metallothionein-II gene, the other a pseudogene, lacking introns, terminating in a poly(A) tail and flanked by two direct repeats. In addition, we have detected a size polymorphism associated with the processed gene in the population, examined, and we have observed a region of apparent secondary structure homology between of 5' flanking region of the functional metallothionein-II gene and that of a mouse metallothionein-I gene.

411 citations


Journal ArticleDOI
TL;DR: The pattern obtained suggests that transition mutations occur somewhat more frequently than transversion mutations and that mutations result more often in A or T than in G or C.
Abstract: The pattern of point mutations is inferred from nucleotide substitutions in pseudogenes. The pattern obtained suggests that transition mutations occur somewhat more frequently than transversion mutations and that mutations result more often in A or T than in G or C. Our results are discussed with respect to the predictions from Topal and Fresco's model for the molecular basis of point (substitution) mutations (Nature 263:285–289, 1976). The pattern of nucleotide substitution at the first and second positions of codons in functional genes is quite similar to that in pseudogenes, but the relative frequency of the transition C→T in the sense strand is drastically reduced and those of the transversions C→G and G→C are doubled. The differences between the two patterns can be explained by the observation that in the protein evolution amino acid substitutions occur mainly between amino acids with similar biochemical properties (Grantham, Science 185:862–864, 1974). Our results for the patterns of nucleotide substitutions in pseudogenes and in functional genes lead to the prediction that both the coding and non-coding regions of protein coding genes should have high frequencies of A and T. Available data show that the non-coding regions are indeed high in A and T but the coding regions are low in T, though high in A.

408 citations


Journal ArticleDOI
23 Dec 1982-Nature
TL;DR: Researchers have studied overlapping cosmids covering two separate regions of the genome, and the gene order in each of these regions was found to be γ–γ–ε–α, which implies an evolutionary duplication in this multigene family involving γ, ε and α genes.
Abstract: Cosmid clones containing the human γ, e and α heavy chain constant region genes and an e pseudogene have been isolated All these genes have a switch sequence detectable by hybridization We have studied overlapping cosmids covering two separate regions of the genome, and the gene order in each of these regions was found to be γ–γ–e–α This implies an evolutionary duplication in this multigene family involving γ, e and α genes

394 citations


Journal ArticleDOI
TL;DR: An approximately 3000 basepair nucleotide sequence in a cloned human DNA fragment is determined that encodes the germline distinct J region segments and it is clear that the mouse J3 sequence, a pseudogene, is not present in the human cluster.

328 citations


Journal ArticleDOI
TL;DR: Restriction mapping experiments and heteroduplex analysis show that c-myc sequences of this locus are interrupted by one intron, suggesting that lambda-LMC-12 and -41 contain the complete functional c- myc gene.
Abstract: We have studied the genomic organization of human cellular sequences (c-myc) homologous to the transforming gene (v-myc) of avian myelocytomatosis virus (MC29). Southern blotting experiments using v-myc probes showed that several fragments of the human genome contain sequences related to the central part of v-myc but only few of them are homologous to the 3' portion of the viral gene. Several recombinant phages which represent different regions of the genome containing c-myc-related sequences were isolated from a human DNA library. Two clones (lambda-LMC-12 and -41) overlap over approximately 17 kilobases of DNA where a sequence homologous to that of the entire v-myc is present. Restriction mapping experiments and heteroduplex analysis show that c-myc sequences of this locus are interrupted by one intron, suggesting that lambda-LMC-12 and -41 contain the complete functional c-myc gene. Three other clones (lambda-LMC-3, -4, and -26) do not overlap and contain sequences related to only approximately 0.3 kilobase of v-myc but lack 5' and 3' portions of the gene. These sequences are not interrupted by introns and are more divergent from v-myc than is the complete gene, suggesting that they may represent either pseudogenes or parts of distantly related genes.

314 citations


Journal ArticleDOI
01 Dec 1982-Cell
TL;DR: Comparison of the human zeta- and alpha-globin gene sequences reveals that the embryonic and adult alpha-like genes began to diverge from each other relatively early in vertebrate evolution.

281 citations


Journal ArticleDOI
01 Mar 1982-Cell
TL;DR: Cloning and Southern blot hybridization analyses indicate that the general organizations of the heavy-chain gene loci of BALB/c and C57BL/6 mice, which have many different serological markers, are fundamentally similar but different in the lengths of S regions.

280 citations


Journal ArticleDOI
TL;DR: The chromosomal location of human constant region light chain immunoglobulin (Ig) genes has been determined by analyzing a group of human fibroblast/rodent somatic cell hybrids with nucleic acid probes prepared from cloned human kappa and lambda constant region genes.
Abstract: The chromosomal location of human constant region light chain immunoglobulin (Ig) genes has been determined by analyzing a group of human fibroblast/rodent somatic cell hybrids with nucleic acid probes prepared from cloned human kappa and lambda constant region genes. Human chromosomes in each cell line were identified by isoenzyme analysis. The DNA from hybrid cells was digested with restriction endonucleases, size fractionated by gel electrophoresis, transferred to nitrocellulose or DBM paper, and hybridized with (32)P-labeled nucleic acid probes. The C(κ) gene was assigned to human chromosome 2 and the C(λ) genes to chromosome 22, based upon analysis of these hybrid cell lines, and these assignments were confirmed by analysis of subclones. A group of previously unassigned loci can be mapped to chromosome 2 by virtue of their close linkage to C(κ). The λ and κ light chain and heavy chain Ig genes have now been assigned to all three human chromosomes that are involved in translocations with chromosome 8 in human B cell neoplasms. These techniques and probes provide a means to study the detailed arrangement of human Ig genes and their pseudogenes.

266 citations


Journal ArticleDOI
01 Jun 1982-Cell
TL;DR: The analyses indicate that the human gamma-gene family has evolved by several types of DNA rearrangemet, including duplication of a complete gene; duplication of an hinge exon; and reassortment of exons by unequal cross-over between two adjacent genes.

238 citations


Journal ArticleDOI
25 Nov 1982-Nature
TL;DR: The rat genome contains two segments closely related to a rat α-tubulin mRNA that are a processed α- Tubulin pseudogene and a dispersed repetitive element inserted within it that possibly reflect a common RNA-mediated process of insertion.
Abstract: The rat genome contains two segments closely related to a rat alpha-tubulin mRNA Both have been cloned and complete nucleotide sequences are presented Analysis of the structure and sequence of one of these establishes it as a functional alpha-tubulin gene The second segment is a processed alpha-tubulin pseudogene Comparison of this pseudogene to the mRNA and gene coding for alpha-tubulin strongly suggests that a mature mRNA was involved in its origin Features of the pseudogene and a dispersed repetitive element inserted within it possibly reflect a common RNA-mediated process of insertion

194 citations


Journal ArticleDOI
01 Jul 1982-Cell
TL;DR: Most of a 9 kb region of the Drosophila genome containing genes for several cuticle proteins has been sequenced and five cuticle-gene-like sequences have been identified and mapped, and they are discussed as a model small gene family.

Journal ArticleDOI
15 Jul 1982-Nature
TL;DR: The present findings demonstrate that avian and mammalian embryonic α genes had a monophyletic origin involving an α locus duplication about 400 Myr ago, and support the view that such globin evolution resulted from natural selection acting on mutations in duplicated genes.
Abstract: Recent years have seen rapid growth in amino acid sequence data on globins and nucleotide sequence data on haemoglobin genes and pseudogenes, and cladistic analysis1 of these data continues to reveal new facets of globin evolution. Our present findings demonstrate: (1) avian and mammalian embryonic α genes (π and ξ, respectively) had a monophyletic origin involving an α locus duplication about 400 Myr ago soon after the duplication which separated α and β genes; (2) much later in phylogeny, independent β-gene duplications produced the embryonic ρ locus of birds and embryonic ɛ and fetal γ loci of mammals. This parallels the earlier finding2 that myoglobins evolved more than once from generalized globin ancestors. Here we support the view2 that such globin evolution resulted from natural selection acting on mutations in duplicated genes. Thus, our evidence contradicts the neutralist view3,4 in which almost all amino acid substitutions in descent to extant globins evaded positive selection.

Journal ArticleDOI
25 Mar 1982-Nature
TL;DR: A dispersed immunoglobulin pseudogene carries two hallmarks of RNA processing—spliced J and C regions and a poly (A)-rich tail and its discovery strengthens the notion that processed genes are a significant feature of the mammalian genome and that genetic information can return to the genome via an RNA intermediate.
Abstract: A dispersed immunoglobulin pseudogene carries two hallmarks of RNA processing—spliced J and C regions and a poly (A)-rich tail. Its discovery strengthens the notion that processed genes are a significant feature of the mammalian genome and that genetic information can return to the genome via an RNA intermediate.

Journal ArticleDOI
02 Dec 1982-Nature
TL;DR: The β-subunit of the human placental glycoprotein hormone, chorionic gonadotropin (HCG), is coded for by at least eight different genes or pseudogenes, four of which are arranged in inverted pairs while the other four are arrangedin tandem pairs.
Abstract: The β-subunit of the human placental glycoprotein hormone, chorionic gonadotropin (HCG), is coded for by at least eight different genes or pseudogenes, four of which are arranged in inverted pairs while the other four are arranged in tandem pairs. The genes are each 1.45 kilobases (kb) long and have two short introns located in identical positions.

Journal ArticleDOI
06 May 1982-Nature
TL;DR: The complete sequence of a human β-tubulin pseudogene is reported, revealing the absence of any intervening sequences, and the presence, in the genome, of an uninterrupted 17 base-pair tract of A residues 14 base-pairs 3′ to a poly(A) signal (AATAAA) signal.
Abstract: Pseudogenes—sequences which are homologous to functional genes but which contain mutational changes precluding the formation of a functional product—seem to be a common feature of eukaryotic genomes. Such sequences were first described in the 5S gene of Xenopus laevis1 and have since been found in several gene families including those of the α- and β-globins of several species2–10, immunoglobulin Vκ genes11, the actin genes of Dictyostelium12 and the small nuclear RNA genes of man13. Among the globin pseudogenes, there appear to be two kinds of structural organization: genes that have retained their intervening sequences4–7 and those that have lost them completely2,3. A possible explanation for the generation of such intron-lacking genes involves the reverse transcription of a processed mRNA to form cDNA, and the introduction of this cDNA copy into the genome either by recombinant heteroduplex formation2, insertion into a staggered chromosomal break3, or via a retrovirus intermediate14. Here we report the complete sequence of a human β-tubulin pseudogene. The sequence data reveal the absence of any intervening sequences, and the presence, in the genome, of an uninterrupted 17 base-pair (bp) tract of A residues 14 base-pairs 3′ to a poly(A) signal (AATAAA)15. This sequence organization corresponds closely to the sequence organization of the poly(A) signal and poly (A) tract in a β-tubulin mRNA16.

Journal ArticleDOI
01 Jun 1982-Cell
TL;DR: The human IgE gene encodes a polypeptide chain that is involved in allergic reactions and in the immune response to parasitic disease in man and appears to have been the site of several complicated genetic rearrangements during recent evolutionary time.

Journal ArticleDOI
TL;DR: The nucleotide sequence of a 9937 base-pair portion of human chromosome 9, which contains two complete leukocyte interferon genes (Leif-L and J), the complete intergenic region, and part of a third related possible pseudogene (LeIF-M), has been determined.

Journal ArticleDOI
TL;DR: It is proposed that both class II and III U1 pseudogenes were generated by an RNA-mediated mechanism involving the insertion of U1 sequence information into a new chromosomal locus.
Abstract: Analysis of cloned human genomic loci homologous to the small nuclear RNA U1 established that such sequences are abundant and dispersed in the human genome and that only a fraction represent bona fide genes. The majority of genomic loci bear defective gene copies, or pseudogenes, which contain scattered base mismatches and in some cases lack the sequence corresponding to the 3' end of U1 RNA. Although all of the U1 genes examined to date are flanked by essentially identical sequences and therefore appear to comprise a single multigene family, the authors present evidence for the existence of at least three structurally distinct classes of U1 pseudogenes. Class I pseudogenes had considerable flanking sequence homology with the U1 gene family and were probably derived from it by a DNA-mediated event such as gene duplication. In contrast, the U1 sequence in class II and III U1 pseudogenes was flanked by single-copy genomic sequences completely unrelated to those flanking the U1 gene family; in addition, short direct repeats flanked the class III but not the class II pseudogene. The authors therefore propose that both class II and III U1 pseudogenes were generated by an RNA-mediated mechanism involving the insertion of U1 sequence informationmore » into a new chromosomal locus. The authors also noted that two other types of repetitive DNA sequences in eucaryotes, the Alu family in vertebrates and the ribosomal DNA insertions in Drosophila, bore a striking structural resemblance to the classes of U1 pseudogenes described here and may have been created by an RNA-mediated insertion event.« less

Journal ArticleDOI
TL;DR: The complete nucleotide sequence of the nonallelic adult goat I alpha- and II alpha-globin genes and, as is the case with the duplicated human alpha-to each other, high homology has most likely been preserved via a gene conversion mechanism.

Journal ArticleDOI
TL;DR: Unge and Strandberg as discussed by the authors used a subculture cloning approach to identify IFN-alpha cDNAs, with characteristic target cell specificities, using the production of an interferon-like protein by transformed bacteria.
Abstract: Copy DNA (cDNA) was prepared from induced leucocyte poly(A) RNA and cloned in Escherichia coli. IFN-alpha cDNA clones were isolated by subculture cloning with the use of a translation hybridization assay. Definitive identification of the clones was based on the production of an interferon-like protein by the transformed bacteria. Different IFN-alpha cDNAs, with characteristic target cell specificities, were identified. The cloned cDNAs typically encode a mature polypeptide of 166 (or, for IFN-alpha 2, 165) amino acids and a signal sequence of 23 amino acids. A human chromosomal library was screened with IFN cDNA and 17 distinct IFN-alpha-related sequences were isolated and identified, of which 7 proved to be nonallelic authentic genes and 4 pseudogenes; 6 sequences remain to be elucidated. Taking into account the work of Goeddel and his colleagues, 13 non-allelic authentic genes and 6 pseudogenes can be distinguished. In addition, 9 genes believed to be allelic to the 13 authentic genes have been sequenced. The IFN-alpha genes may be classified into two major subfamilies, which diverged at least 33 Ma ago, but perhaps much earlier, if sequence rectification occurred. At least one IFN-alpha gene appears to have resulted by a recombinational event between members of the subfamily I and II. IFN-beta is distantly related to IFN-alpha's and may have diverged from a common ancestor at least 500 Ma ago. Both IFN-alpha and IFN-beta genes differ from most other genes of higher organisms by being devoid of introns. The mouse was found to possess an IFN-alpha gene family of a size similar to that of man; the murine genes also do not have introns. IFN-alpha genes devoid of their signal sequence were joined to prokaryotic promoters to produce the mature interferons in E. coli in high yield. IFN-alpha 2, purified to homogeneity, has been crystallized by T. Unge and B. Strandberg (Uppsala). Hybrid genes consisting of IFN-alpha 1 and IFN-alpha 2 segments were constructed and expressed in E. coli; the target cell specificities of such hybrids were dependent on the arrangement of the segments and were different from those of either parent. The chromosomal gene for HuIFN-alpha 1 was introduced into mouse L cells to study the mechanism of its expression. Correct transcription was only detected after induction (with Newcastle disease virus); expression was transient, with the same kinetics as those of the endogenous mouse IFN mRNA. Natural murine IFNs and human IFN-beta and IFN-gamma are glycosylated. Because E. coli cells transformed with the genes of eukaryotic glycoproteins are not expected to yield correctly glycosylated polypeptides, we prepared lines of hamster cells permanently transformed with hybrid plasmids, which contained an IFN gene linked to the SV40 early promoter, as well as dihydrofolate reductase as a selective marker. After intracellular amplification of the introduced genes, cell lines were obtained which constitutively produced IFN at about 40 000 units ml-1 and could be propagated for at least several months.

Journal ArticleDOI
04 Feb 1982-Nature
TL;DR: Nucleotide sequence analysis indicates that Cλ4 is not expressed due to an inactive RNA splice site, and substitutions in the rearrangement recognition sequences associated with Jλ2 and Jλ3 segments, together with nearby competing pseudo recognition sequences, may explain the relatively low levels of C λ2 and Cλ3 gene expression.
Abstract: Immunoglobulin λ light chains in the mouse comprise three types: λ1, λ2 and λ3 (refs 1–3 respectively) and are encoded by three constant region (Cλ) and two variable region (Vλ) genes. The Cλ2 and Cλ3 protein sequences differ at only 5 amino acid positions whereas Cλ1 differs from both by about 30 amino acids. The Cλ1 and Cλ3 genes are closely linked4, separated by ∼3 kilobases (kb) of DNA. The Cλ2 gene is closely linked to a Cλ4 gene, but is an unknown distance from the Cλ3–Cλ1 cluster4,5. Although the Cλ4 gene shares homology with Cλ1, we show here that it represents a pseudogene. Only two germ-line V genes appear to be expressed in mouse λ chains: Vλ1 is used in association with either Cλ1 (ref. 1) or Cλ3 (ref. 6), while Vλ2 has only been found with Cλ2 (ref. 2). Differential gene expression is observed in the λ locus. Among mouse serum antibodies, λ1 chains occur 10 times more frequently than λ2 (ref. 7) or λ3 (ref. 3) chains while λ4 chains have not been identified. We have now searched for structural differences between Cλ genes which could explain this differential expression. Our nucleotide sequence analysis indicates that Cλ4 is not expressed due to an inactive RNA splice site. Although no structural defects were found in Cλ2 or Cλ3, substitutions in the rearrangement recognition sequences associated with Jλ2 and Jλ3 segments, together with nearby competing pseudo recognition sequences, may explain the relatively low levels of Cλ2 and Cλ3 gene expression.

Journal ArticleDOI
TL;DR: It is proposed that both simple DNA sequences and homology in flanking regions serve a function in the correction of VH genes, which seem to be rather free to diverge and drift into pseudogenes.
Abstract: Five closely related immunoglobulin VH genes (subgroup II) were compared by sequencing of several kb of DNA. In three of the genes homology greater than 75% was found along an area of 4 kb that includes the coding region. The homology in flanking regions is only slightly lower than that in the coding sequences. Two other genes, which are located on the same EcoRI fragment, show high homology to the first three genes in the coding and immediately flanking regions. In more distant flanking regions no homology is found with the first three genes. This indicates that their evolutionary history differs from that of the other three genes. A region of simple DNA sequence composed of repetitive TCC and TCA elements was found at a distance of approximately 380 bp upstream from the initiator ATG of these VH genes. This region is the site where the two sets of genes abruptly start to diverge. The structure of the simple DNA sequence in the various VH genes suggests that it may be involved in gene interaction. We propose that both simple DNA sequences and homology in flanking regions serve a function in the correction of VH genes, which seem to be rather free to diverge and drift into pseudogenes. A correction mechanism may help this gene family to maintain its two major features, multiplicity and diversity.

Journal ArticleDOI
06 Aug 1982-Science
TL;DR: The sequence of two human beta-tubulin pseudogenes is described, one of which contains an intervening sequence but lacks sequences encoding the 55 N-terminal amino acids of the polypeptide chain.
Abstract: The sequence of two human beta-tubulin pseudogenes is described. One contains an intervening sequence but lacks sequences encoding the 55 N-terminal amino acids of the polypeptide chain. A second has no introns but has a polyadenylate signal and an oligoadenylate tract at its 3' end, and it is flanked by a short direct repeat. These sequences have arisen by different mechanisms, including one that probably involves reverse transcription of a processed messenger RNA and reintegration of the complementary DNA copy into the genome.

Journal ArticleDOI
TL;DR: An active human epsilon chain gene was cloned from a phage library containing partial EcoRI digests of IgE-producing myeloma DNA, using the human JH (joining) gene fragment as a probe and identified by partial nucleotide sequence determination.
Abstract: An active human epsilon chain gene was cloned from a phage library containing partial EcoRI digests of IgE-producing myeloma DNA, using the human JH (joining) gene fragment as a probe. The epsilon chain gene clone was identified by partial nucleotide sequence determination. The germ-line constant region gene of the epsilon chain (C epsilon gene) was cloned from a human fetal liver DNA library, using the cloned epsilon chain gene as a probe. Comparative studies on the human and mouse germ-line epsilon chain genes revealed that the switch (S) sequence is more conserved than the coding sequence. Restriction endonuclease BamHI digestion of human DNA produced three C epsilon fragments of 3.0, 6.5, and 9.2 kilobases, which were named C epsilon 1, C epsilon 2, and C epsilon 3 genes, respectively. We found the three C epsilon gene fragments in all of the human DNA preparations from eleven individuals. The C epsilon gene expressed in the myeloma was identified as the C epsilon 1 gene. Because the C epsilon 2 gene is deleted from the myeloma DNA, the order of the C epsilon genes is likely to be 5'-C epsilon 2-C epsilon 1-C epsilon 3-3', assuming that all the C epsilon genes are on chromosome 14. The germ-line C epsilon 3 gene was also cloned from the myeloma DNA. Characterization of the C epsilon 3 gene revealed that it does not have the S region, suggesting that it might be a pseudogene.

Journal ArticleDOI
TL;DR: The δ-globin gene, which has been silenced on at least two separate occasions in primate evolution (in lemurs and in old world monkeys), is suggested to be present in most or all primates.

Journal ArticleDOI
01 Dec 1982-Gene
TL;DR: To understand the organization of the human leukocyte antigen (HLA) gene region and its relationship to the transplantation antigens expressed at the cell surface the authors have isolated clones containing HLA class I genes from a cosmid library constructed with the DNA from an individual of defined haplotype.

Journal ArticleDOI
04 Feb 1982-Nature
TL;DR: It is reported here that retrovirus-like elements are located on both sides of the αψ3 gene, which has precisely lost the intervening sequences characteristic of the functional genes.
Abstract: Mice have three functional α-globin genes and two closely related pseudogenes1–5. In BALB/c mice, the functional genes are known to be clustered on chromosome 11, but the pseudo-genes, designated αψ3 and αψ4, are located on chromosomes 15 and 17, respectively5. One of the pseudogenes, αψ3, has precisely lost the intervening sequences characteristic of the functional genes3,4, as if it had been generated from a processed RNA intermediate. It has been suggested that retroviral functions could have been instrumental in the formation of this ‘spliceless’ pseudogene6 and its integration at a novel chromosomal locus5. We report here that retrovirus-like elements are located on both sides of the αψ3 gene.

Journal ArticleDOI
TL;DR: The tRNA-coding locus of the 8.2-kilobase pair Eco RI fragments Eco G of Euglena gracilis Klebs, strain Z Pringsheim chloroplast DNA was chosen for detailed analysis, and four tRNA genes were identified from the DNA sequence.

Journal ArticleDOI
TL;DR: The results show that the C epsilon 3 gene lacks the three intervening sequences entirely and has a 31‐base A‐rich sequence 16 bases 3′ to the putative poly(A) addition signal, indicating that the TATAAA and AATAAA sequences as well as terminal inverted repeats sequences are present in both 5‐ and 3‐flanking regions.
Abstract: There are at least three immunoglobulin epsilon genes (C epsilon 1, C epsilon 2, and C epsilon 3) in the human genome. The nucleotide sequences of the expressed epsilon gene (C epsilon 1) and one (C epsilon 3) of the two epsilon pseudogenes were compared. The results show that the C epsilon 3 gene lacks the three intervening sequences entirely and has a 31-base A-rich sequence 16 bases 3' to the putative poly(A) addition signal, indicating that the C epsilon 3 gene is a processed gene. The C epsilon 3 gene sequence is homologous to the five separate DNA segments of the C epsilon 1 gene; namely, a segment in the 5'-flanking region (100 bases) and four exons, which are interrupted by a spacer region or intervening sequences. Long terminal repeat (LTR)-like sequences which contain TATAAA and AATAAA sequences as well as terminal inverted repeats are present in both 5'- and 3'-flanking regions. The 5' and 3' LTR-like sequences do not, however, constitute a direct repeat, unlike transposable elements of eukaryotes and retroviruses. The 3' LTR-like sequence is repetitive in the human genome, but is not homologous to the Alu family DNA. Models for the evolutionary origin of the processed gene flanked by the LTR-like sequences are discussed. The C epsilon 3 gene has a new open frame which codes potentially for an unknown protein of 292 amino acid residues.

Journal ArticleDOI
14 Jan 1982-Nature
TL;DR: It is reported here that all eight known IFN-α genes diverged from a common ancestor quite recently, at most ∼26 Myr ago, which suggests that the IFn-α multigene family in primates is distinct in organization from that of other mammals.
Abstract: The two major classes of human type I interferons, leukocyte or α-interferon (IFN-α) and fibroblastor β-interferon (IFN-β) are antigenically distinct and encoded by separate structural genes1. Recently, genomic hybridization experiments have demonstrated the presence of ∼10 or more distinct human IFN-α (Hu IFN-α) genes which code for a family of homologous yet distinct proteins2,3, and 8 of these have been identified and sequenced3. In contrast, no evidence has been found for multiple Hu IFN-β genes3, although heterogeneity of Hu IFN-β mRNA has been observed4,5. The coding sequences of Hu IFN-α and IFN-β genes show weak but appreciable homology, indicating that they were derived from a common ancestor at a remote time6, whereas Hu IFN-α1 (a member of class D) and Hu IFN-α2 (a member of class A) diverged quite recently (∼22 Myr ago)7. We report here that all eight known IFN-α genes diverged from a common ancestor quite recently, at most ∼26 Myr ago. As mammalian divergence is known to have occurred ∼75 Myr ago8, this suggests that the IFN-α multigene family in primates is distinct in organization from that of other mammals. We provide evidence for a much lower rate of evolution for IFN-α G than for other α-interferons, and a rapid evolution of IFN-α E pseudogene similar to that of other pseudogenes9–11. A possible evolutionary origin of size heterogeneity in the 3′-noncoding region of IFN-α mRNAs is also discussed.