Intraspecific nucleotide sequence variability surrounding the origin of replication in human mitochondrial DNA

Barry Greenberg, John E. Newbold, Akio Sugino

Research output: Contribution to journalArticle

Abstract

We have cloned the major noncoding region of human mitochondrial DNA (mtDNA) from 11 human placentas. Partial nucleotide sequences of five of these clones have been determined and they share a maximum of 900 bp around the origin of H-strand replication. Alignment of these sequences with others previously determined has revealed a striking pattern of nucleotide substitutions and insertion/deletion events. The level of sequence divergence significantly exceeds the reported estimates of divergence in coding regions. Two particularly hypervariable regions have also been defined. More than 96% of the base changes are transitions, and length alterations have occurred exclusively by addition or deletion of mono- or dinucleotide segments within serially repeating stretches. This region of the mitochondrial genome, which contains the initiation sites for replication and transcription, is the least conserved among species with respect to both sequence and length (Anderson et al., 1981; Walberg and Clayton, 1981). Despite this overall lack of primary sequence conservation, several consistencies appear among the available mammalian mtDNA sequences within this region. Between species, a conserved linear array of characteristic stretches exists which nonetheless differ in primary sequence. Among humans, several conserved blocks of nucleotides appear within domains deleted from the mtDNA of other species. These observations are consistent with both a species-specificity of nucleotide sequence, and a preservation of the necessary genetic functions among species. This provides a model for the evolution of protein-nucleic acid interactions in mammalian mitochondria.

Original languageEnglish (US)
Pages (from-to)33-49
Number of pages17
JournalGene
Volume21
Issue number1-2
DOIs
StatePublished - Jan 1 1983
Externally publishedYes

Fingerprint

Replication Origin
Mitochondrial DNA
Nucleotides
Species Specificity
Mitochondrial Genome
Sequence Alignment
Transcription Initiation Site
Nucleic Acids
Placenta
Mitochondria
Clone Cells
Proteins

Keywords

  • deletions
  • hypervariable regions
  • Insertions
  • nucleotide substitutions

ASJC Scopus subject areas

  • Genetics

Cite this

Intraspecific nucleotide sequence variability surrounding the origin of replication in human mitochondrial DNA. / Greenberg, Barry; Newbold, John E.; Sugino, Akio.

In: Gene, Vol. 21, No. 1-2, 01.01.1983, p. 33-49.

Research output: Contribution to journalArticle

@article{97b20ec78f4c4d0db753cb4c48cec57b,
title = "Intraspecific nucleotide sequence variability surrounding the origin of replication in human mitochondrial DNA",
abstract = "We have cloned the major noncoding region of human mitochondrial DNA (mtDNA) from 11 human placentas. Partial nucleotide sequences of five of these clones have been determined and they share a maximum of 900 bp around the origin of H-strand replication. Alignment of these sequences with others previously determined has revealed a striking pattern of nucleotide substitutions and insertion/deletion events. The level of sequence divergence significantly exceeds the reported estimates of divergence in coding regions. Two particularly hypervariable regions have also been defined. More than 96{\%} of the base changes are transitions, and length alterations have occurred exclusively by addition or deletion of mono- or dinucleotide segments within serially repeating stretches. This region of the mitochondrial genome, which contains the initiation sites for replication and transcription, is the least conserved among species with respect to both sequence and length (Anderson et al., 1981; Walberg and Clayton, 1981). Despite this overall lack of primary sequence conservation, several consistencies appear among the available mammalian mtDNA sequences within this region. Between species, a conserved linear array of characteristic stretches exists which nonetheless differ in primary sequence. Among humans, several conserved blocks of nucleotides appear within domains deleted from the mtDNA of other species. These observations are consistent with both a species-specificity of nucleotide sequence, and a preservation of the necessary genetic functions among species. This provides a model for the evolution of protein-nucleic acid interactions in mammalian mitochondria.",
keywords = "deletions, hypervariable regions, Insertions, nucleotide substitutions",
author = "Barry Greenberg and Newbold, {John E.} and Akio Sugino",
year = "1983",
month = "1",
day = "1",
doi = "10.1016/0378-1119(83)90145-2",
language = "English (US)",
volume = "21",
pages = "33--49",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Intraspecific nucleotide sequence variability surrounding the origin of replication in human mitochondrial DNA

AU - Greenberg, Barry

AU - Newbold, John E.

AU - Sugino, Akio

PY - 1983/1/1

Y1 - 1983/1/1

N2 - We have cloned the major noncoding region of human mitochondrial DNA (mtDNA) from 11 human placentas. Partial nucleotide sequences of five of these clones have been determined and they share a maximum of 900 bp around the origin of H-strand replication. Alignment of these sequences with others previously determined has revealed a striking pattern of nucleotide substitutions and insertion/deletion events. The level of sequence divergence significantly exceeds the reported estimates of divergence in coding regions. Two particularly hypervariable regions have also been defined. More than 96% of the base changes are transitions, and length alterations have occurred exclusively by addition or deletion of mono- or dinucleotide segments within serially repeating stretches. This region of the mitochondrial genome, which contains the initiation sites for replication and transcription, is the least conserved among species with respect to both sequence and length (Anderson et al., 1981; Walberg and Clayton, 1981). Despite this overall lack of primary sequence conservation, several consistencies appear among the available mammalian mtDNA sequences within this region. Between species, a conserved linear array of characteristic stretches exists which nonetheless differ in primary sequence. Among humans, several conserved blocks of nucleotides appear within domains deleted from the mtDNA of other species. These observations are consistent with both a species-specificity of nucleotide sequence, and a preservation of the necessary genetic functions among species. This provides a model for the evolution of protein-nucleic acid interactions in mammalian mitochondria.

AB - We have cloned the major noncoding region of human mitochondrial DNA (mtDNA) from 11 human placentas. Partial nucleotide sequences of five of these clones have been determined and they share a maximum of 900 bp around the origin of H-strand replication. Alignment of these sequences with others previously determined has revealed a striking pattern of nucleotide substitutions and insertion/deletion events. The level of sequence divergence significantly exceeds the reported estimates of divergence in coding regions. Two particularly hypervariable regions have also been defined. More than 96% of the base changes are transitions, and length alterations have occurred exclusively by addition or deletion of mono- or dinucleotide segments within serially repeating stretches. This region of the mitochondrial genome, which contains the initiation sites for replication and transcription, is the least conserved among species with respect to both sequence and length (Anderson et al., 1981; Walberg and Clayton, 1981). Despite this overall lack of primary sequence conservation, several consistencies appear among the available mammalian mtDNA sequences within this region. Between species, a conserved linear array of characteristic stretches exists which nonetheless differ in primary sequence. Among humans, several conserved blocks of nucleotides appear within domains deleted from the mtDNA of other species. These observations are consistent with both a species-specificity of nucleotide sequence, and a preservation of the necessary genetic functions among species. This provides a model for the evolution of protein-nucleic acid interactions in mammalian mitochondria.

KW - deletions

KW - hypervariable regions

KW - Insertions

KW - nucleotide substitutions

UR - http://www.scopus.com/inward/record.url?scp=0020527670&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020527670&partnerID=8YFLogxK

U2 - 10.1016/0378-1119(83)90145-2

DO - 10.1016/0378-1119(83)90145-2

M3 - Article

C2 - 6301949

AN - SCOPUS:0020527670

VL - 21

SP - 33

EP - 49

JO - Gene

JF - Gene

SN - 0378-1119

IS - 1-2

ER -