Abstract
The I region of the major histocompatibility complex (MHC) of the mouse (H-2) contains a tightly-linked cluster of highly poly-morphic genes (class II MHC genes) which control immune responsiveness. Speculation on the origin of this polymorphism, which is believed to be essential for the function of the class II proteins in immune responses to disease, has given rise to two hypotheses. The first is that hypermutational mechanisms (gene conversion or segmental exchange) promote the rapid generation of diversity in MHC genes. The alternative is that polymorphism has arisen from the steady accumulation of mutations over long evolutionary peri-ods, and multiple specific alleles have survived speciation (trans-species evolution). We have looked for evidence of 'segmental exchange' and/or 'trans-species evolution' in the class II genes of the genus Mus by molecular genetic analysis of I-Aβ alleles. The results indicate that >90% (28 out of 31) of the alleles examined can be organized into two evolutionary groups both on the basis of restriction site polymorphisms and by the presence or absence of a short interspersed nucleotide element (SINE). Using this SINE sequence as an evolutionary tag, we demonstrate that I-Aβ alleles in these two evolutionary groups diverged at least three million years ago and have survived the speciation events leading to several modern Mus species. Nucleotide sequence comparisons of eight Mus m. domesticus I-Aβ alleles representing all three evolutionary groups indicate that most of the divergence in exon sequences is due to the steady accumulation of mutations that are maintained independently in the different alleles. But segmental exchanges between alleles from different evolutionary groups have also played a role in the diversification of β1, exons.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 651-654 |
| Number of pages | 4 |
| Journal | Nature |
| Volume | 332 |
| Issue number | 6165 |
| DOIs | |
| State | Published - Jan 1 1988 |
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The origin of MHC class II gene polymorphism within the genus Mus. / McConnell, Thomas J.; Talbot, William S.; McIndoe, Richard A; Wakeland, Edward K.
In: Nature, Vol. 332, No. 6165, 01.01.1988, p. 651-654.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The origin of MHC class II gene polymorphism within the genus Mus
AU - McConnell, Thomas J.
AU - Talbot, William S.
AU - McIndoe, Richard A
AU - Wakeland, Edward K.
PY - 1988/1/1
Y1 - 1988/1/1
N2 - The I region of the major histocompatibility complex (MHC) of the mouse (H-2) contains a tightly-linked cluster of highly poly-morphic genes (class II MHC genes) which control immune responsiveness. Speculation on the origin of this polymorphism, which is believed to be essential for the function of the class II proteins in immune responses to disease, has given rise to two hypotheses. The first is that hypermutational mechanisms (gene conversion or segmental exchange) promote the rapid generation of diversity in MHC genes. The alternative is that polymorphism has arisen from the steady accumulation of mutations over long evolutionary peri-ods, and multiple specific alleles have survived speciation (trans-species evolution). We have looked for evidence of 'segmental exchange' and/or 'trans-species evolution' in the class II genes of the genus Mus by molecular genetic analysis of I-Aβ alleles. The results indicate that >90% (28 out of 31) of the alleles examined can be organized into two evolutionary groups both on the basis of restriction site polymorphisms and by the presence or absence of a short interspersed nucleotide element (SINE). Using this SINE sequence as an evolutionary tag, we demonstrate that I-Aβ alleles in these two evolutionary groups diverged at least three million years ago and have survived the speciation events leading to several modern Mus species. Nucleotide sequence comparisons of eight Mus m. domesticus I-Aβ alleles representing all three evolutionary groups indicate that most of the divergence in exon sequences is due to the steady accumulation of mutations that are maintained independently in the different alleles. But segmental exchanges between alleles from different evolutionary groups have also played a role in the diversification of β1, exons.
AB - The I region of the major histocompatibility complex (MHC) of the mouse (H-2) contains a tightly-linked cluster of highly poly-morphic genes (class II MHC genes) which control immune responsiveness. Speculation on the origin of this polymorphism, which is believed to be essential for the function of the class II proteins in immune responses to disease, has given rise to two hypotheses. The first is that hypermutational mechanisms (gene conversion or segmental exchange) promote the rapid generation of diversity in MHC genes. The alternative is that polymorphism has arisen from the steady accumulation of mutations over long evolutionary peri-ods, and multiple specific alleles have survived speciation (trans-species evolution). We have looked for evidence of 'segmental exchange' and/or 'trans-species evolution' in the class II genes of the genus Mus by molecular genetic analysis of I-Aβ alleles. The results indicate that >90% (28 out of 31) of the alleles examined can be organized into two evolutionary groups both on the basis of restriction site polymorphisms and by the presence or absence of a short interspersed nucleotide element (SINE). Using this SINE sequence as an evolutionary tag, we demonstrate that I-Aβ alleles in these two evolutionary groups diverged at least three million years ago and have survived the speciation events leading to several modern Mus species. Nucleotide sequence comparisons of eight Mus m. domesticus I-Aβ alleles representing all three evolutionary groups indicate that most of the divergence in exon sequences is due to the steady accumulation of mutations that are maintained independently in the different alleles. But segmental exchanges between alleles from different evolutionary groups have also played a role in the diversification of β1, exons.
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U2 - 10.1038/332651a0
DO - 10.1038/332651a0
M3 - Article
C2 - 2895893
AN - SCOPUS:0023887073
VL - 332
SP - 651
EP - 654
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6165
ER -