DOI: 10.1073/pnas.94.15.7799. Evolution by the birth-and-death process in multigene families of the vertebrate immune system

Evolution by the birth-and-death process in multigene families of the vertebrate immune system

10.1073/pnas.94.15.7799

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Concerted evolution is often invoked to explain the diversity and evolution of the multigene families of major histocompatibility complex (MHC) genes and immunoglobulin (Ig) genes. However, this hypothesis has been controversial because the member genes of these families from the same species are not necessarily more closely related to one another than to the genes from different species. To resolve this controversy, we conducted phylogenetic analyses of several multigene families of the MHC and Ig systems. The results show that the evolutionary pattern of these families is quite different from that of concerted evolution but is in agreement with the birth-and-death model of evolution in which new genes are created by repeated gene duplication and some duplicate genes are maintained in the genome for a long time but others are deleted or become nonfunctional by deleterious mutations. We found little evidence that interlocus gene conversion plays an important role in the evolution of MHC and Ig multigene families.

Bibliography

Nei, M., Gu, X., & Sitnikova, T. (1997). Evolution by the birth-and-death process in multigene families of the vertebrate immuneâsystem. Proceedings of the National Academy of Sciences, 94(15), 7799â7806.

Authors 3

Masatoshi Nei (first)
Xun Gu (additional)
Tatyana Sitnikova (additional)

References 73 Referenced 625

10.1101/SQB.1974.038.01.055
10.1073/pnas.77.4.2158
10.1016/S0021-9258(19)34066-9
N Arnheim Evolution of Genes and Proteins, eds M Nei, R K Koehn (Sinauer, Sunderland, MA), pp. 38–61 (1983). / Evolution of Genes and Proteins by Arnheim N (1983)
10.1038/301671a0
10.1073/pnas.88.15.6716
10.1073/pnas.87.6.2167
10.1146/annurev.ge.09.120175.001513
10.1016/0092-8674(83)90508-1
10.1128/mcb.13.2.821-830.1993
10.1016/0040-5809(83)90015-1
T Gojobori, M Nei Mol Biol Evol 1, 195–212 (1984). / Mol Biol Evol by Gojobori T (1984)
A L Hughes, M Nei Mol Biol Evol 6, 559–579 (1989). / Mol Biol Evol by Hughes A L (1989)
T Ota, M Nei Mol Biol Evol 11, 469–482 (1994). / Mol Biol Evol by Ota T (1994)
M Nei, A L Hughes Evolution at the Molecular Level, eds R Selander, A Clark, T Whittam (Sinauer, Sunderland, MA), pp. 222–247 (1991). / Evolution at the Molecular Level by Nei M (1991)
M Nei, A L Hughes 11th Histocompatibility Workshop and Conference, eds K Tsuji, M Aizawa, T Sasazuki (Oxford Univ. Press, Oxford) 2, 27–38 (1992). / 11th Histocompatibility Workshop and Conference by Nei M (1992)
10.1002/eji.1830231121
10.1007/BF02602651
10.1126/science.272.5258.67
10.1073/pnas.94.4.1384
10.1038/ng0896-399
10.1007/BF00188427
10.1073/pnas.91.14.6251
10.1002/j.1460-2075.1985.tb03692.x
J Klein, F Figueroa Crit Rev Immunol 6, 295–386 (1986). / Crit Rev Immunol by Klein J (1986)
10.1093/genetics/122.3.681
A L Hughes, M Nei Mol Biol Evol 7, 491–514 (1990). / Mol Biol Evol by Hughes A L (1990)
J Klein Natural History of the Major Histocompatibility Complex (Wiley, New York, 1986). / Natural History of the Major Histocompatibility Complex by Klein J (1986)
P W Hedrick, T J Kim Evolutionary Genetics from Molecules to Morphology, eds R S Singh, C K Krimbas (Cambridge Univ. Press, New York, , in press. (1997). / Evolutionary Genetics from Molecules to Morphology by Hedrick P W (1997)
10.1038/335167a0
10.1098/rstb.1994.0115
10.1038/357329a0
10.1007/BF02602779
10.1038/310650a0
S Kumar, K Tamura, M Nei mega: Molecular Evolutionary Genetic Analysis (Pennsylvania State Univ., University Park, 1993). / mega: Molecular Evolutionary Genetic Analysis by Kumar S (1993)
10.1146/annurev.iy.08.040190.000323
J Zemmour, B H Koller, P D Ennis, D E Geraghty, D A Lawlor, H T Orr, P Parham J Immunol 144, 3619–3629 (1990). (10.4049/jimmunol.144.9.3619) / J Immunol by Zemmour J (1990)
D E Geraghty, B H Koller, J Pei, J A Hansen J Immunol 149, 1947–1957 (1992). (10.4049/jimmunol.149.6.1947) / J Immunol by Geraghty D E (1992)
10.1146/annurev.genet.30.1.371
10.1007/BF00216696
10.1007/BF00176441
10.1093/genetics/115.1.161
Z W Chen, S N McAdam, A L Hughes, A L Dogon, N L Letvin, D I Watkins J Immunol 148, 2547–2554 (1992). (10.4049/jimmunol.148.8.2547) / J Immunol by Chen Z W (1992)
10.1038/381226a0
S Schneider, V Vincek, H Tichy, F Figueroa, J Klein Mol Biol Evol 8, 753–766 (1991). / Mol Biol Evol by Schneider S (1991)
R W Slade, W E Mayer Mol Biol Evol 12, 441–450 (1995). / Mol Biol Evol by Slade R W (1995)
T Tanaka, M Nei Mol Biol Evol 6, 447–459 (1989). / Mol Biol Evol by Tanaka T (1989)
10.1016/0888-7543(95)80201-V
10.1172/JCI118198
10.1016/B978-012053640-5/50011-2
10.1038/ng0694-162
10.1038/ng0193-88
10.1016/B978-012053640-5/50010-0
I M Tomlinson, S C Williams, O Ignatovich, S J Corbertt, G Winter v base Sequence Directory (MRC Centre for Protein Engineering, Cambridge, U.K., 1996). / v base Sequence Directory by Tomlinson I M (1996)
10.1093/intimm/2.1.41
10.1006/jmbi.1996.0636
10.1016/0923-2494(96)87226-9
10.1007/BF00188170
10.1016/0092-8674(89)90879-9
10.1016/B978-012053640-5/50016-1
V Dufour, S Malinge, N Francois J Immunol 156, 2163–2170 (1996). (10.4049/jimmunol.156.6.2163) / J Immunol by Dufour V (1996)
10.1093/oxfordjournals.molbev.a040194
10.1146/annurev.iy.09.040191.001251
10.1038/302575a0
10.1016/0092-8674(80)90426-2
10.1002/j.1460-2075.1985.tb04013.x
A L Hughes Mol Biol Evol 12, 247–258 (1995). / Mol Biol Evol by Hughes A L (1995)
10.1038/221040a0
J Klein, H Ono, D Klein, C O’hUigin Prog Immunol 8, 137–143 (1993). / Prog Immunol by Klein J (1993)
10.1016/0378-1119(95)00627-3
J Sun, I Kacskovics, W R Brown, J E Butler J Immunol 153, 5618–5627 (1994). (10.4049/jimmunol.153.12.5618) / J Immunol by Sun J (1994)
10.1111/j.1749-6632.1995.tb55845.x
K H Roux, P Dhanarajan, V Gottschalk, W T McCormack, R W Renshaw J Immunol 146, 2027–2036 (1991). (10.4049/jimmunol.146.6.2027) / J Immunol by Roux K H (1991)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:05 a.m.)
Indexed	1 day, 15 hours ago (Sept. 4, 2025, 9:11 a.m.)
Issued	28 years, 1 month ago (July 22, 1997)
Published	28 years, 1 month ago (July 22, 1997)
Published Online	28 years, 1 month ago (July 22, 1997)
Published Print	28 years, 1 month ago (July 22, 1997)

Funders 0

None

BibTeX

@article{Nei_1997, title={Evolution by the birth-and-death process in multigene families of the vertebrate immune system}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.15.7799}, DOI={10.1073/pnas.94.15.7799}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Nei, Masatoshi and Gu, Xun and Sitnikova, Tatyana}, year={1997}, month=jul, pages={7799–7806} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        9,
        4
      ]
    ],
    "date-time": "2025-09-04T13:11:43Z",
    "timestamp": 1756991503817
  },
  "reference-count": 73,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "15",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1997,
        7,
        22
      ]
    ]
  },
  "abstract": "<jats:p>Concerted evolution is often invoked to explain the diversity and evolution of the multigene families of major histocompatibility complex (MHC) genes and immunoglobulin (Ig) genes. However, this hypothesis has been controversial because the member genes of these families from the same species are not necessarily more closely related to one another than to the genes from different species. To resolve this controversy, we conducted phylogenetic analyses of several multigene families of the MHC and Ig systems. The results show that the evolutionary pattern of these families is quite different from that of concerted evolution but is in agreement with the birth-and-death model of evolution in which new genes are created by repeated gene duplication and some duplicate genes are maintained in the genome for a long time but others are deleted or become nonfunctional by deleterious mutations. We found little evidence that interlocus gene conversion plays an important role in the evolution of MHC and Ig multigene families.</jats:p>",
  "DOI": "10.1073/pnas.94.15.7799",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T14:31:44Z",
    "timestamp": 1027693904000
  },
  "page": "7799-7806",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 625,
  "title": "Evolution by the birth-and-death process in multigene families of the vertebrate immune\u2009system",
  "prefix": "10.1073",
  "volume": "94",
  "author": [
    {
      "given": "Masatoshi",
      "family": "Nei",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Institute of Molecular Evolutionary Genetics and Department of Biology, The Pennsylvania State University, 328 Mueller Laboratory, University Park, PA 16802"
        }
      ]
    },
    {
      "given": "Xun",
      "family": "Gu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Molecular Evolutionary Genetics and Department of Biology, The Pennsylvania State University, 328 Mueller Laboratory, University Park, PA 16802"
        }
      ]
    },
    {
      "given": "Tatyana",
      "family": "Sitnikova",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institute of Molecular Evolutionary Genetics and Department of Biology, The Pennsylvania State University, 328 Mueller Laboratory, University Park, PA 16802"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        1997,
        7,
        22
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_3_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/SQB.1974.038.01.055"
    },
    {
      "key": "e_1_3_3_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.77.4.2158"
    },
    {
      "key": "e_1_3_3_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(19)34066-9"
    },
    {
      "key": "e_1_3_3_4_2",
      "first-page": "38",
      "volume-title": "Evolution of Genes and Proteins",
      "author": "Arnheim N",
      "year": "1983",
      "unstructured": "N Arnheim Evolution of Genes and Proteins, eds M Nei, R K Koehn (Sinauer, Sunderland, MA), pp. 38\u201361 (1983)."
    },
    {
      "key": "e_1_3_3_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/301671a0"
    },
    {
      "key": "e_1_3_3_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.88.15.6716"
    },
    {
      "key": "e_1_3_3_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.87.6.2167"
    },
    {
      "key": "e_1_3_3_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.ge.09.120175.001513"
    },
    {
      "key": "e_1_3_3_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(83)90508-1"
    },
    {
      "key": "e_1_3_3_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.13.2.821-830.1993"
    },
    {
      "key": "e_1_3_3_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0040-5809(83)90015-1"
    },
    {
      "key": "e_1_3_3_12_2",
      "first-page": "195",
      "volume": "1",
      "author": "Gojobori T",
      "year": "1984",
      "unstructured": "T Gojobori, M Nei Mol Biol Evol 1, 195\u2013212 (1984).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_13_2",
      "first-page": "559",
      "volume": "6",
      "author": "Hughes A L",
      "year": "1989",
      "unstructured": "A L Hughes, M Nei Mol Biol Evol 6, 559\u2013579 (1989).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_14_2",
      "first-page": "469",
      "volume": "11",
      "author": "Ota T",
      "year": "1994",
      "unstructured": "T Ota, M Nei Mol Biol Evol 11, 469\u2013482 (1994).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_15_2",
      "first-page": "222",
      "volume-title": "Evolution at the Molecular Level",
      "author": "Nei M",
      "year": "1991",
      "unstructured": "M Nei, A L Hughes Evolution at the Molecular Level, eds R Selander, A Clark, T Whittam (Sinauer, Sunderland, MA), pp. 222\u2013247 (1991)."
    },
    {
      "key": "e_1_3_3_16_2",
      "first-page": "27",
      "volume-title": "11th Histocompatibility Workshop and Conference",
      "author": "Nei M",
      "year": "1992",
      "unstructured": "M Nei, A L Hughes 11th Histocompatibility Workshop and Conference, eds K Tsuji, M Aizawa, T Sasazuki (Oxford Univ. Press, Oxford) 2, 27\u201338 (1992)."
    },
    {
      "key": "e_1_3_3_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/eji.1830231121"
    },
    {
      "key": "e_1_3_3_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF02602651"
    },
    {
      "key": "e_1_3_3_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.272.5258.67"
    },
    {
      "key": "e_1_3_3_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.94.4.1384"
    },
    {
      "key": "e_1_3_3_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng0896-399"
    },
    {
      "key": "e_1_3_3_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00188427"
    },
    {
      "key": "e_1_3_3_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.14.6251"
    },
    {
      "key": "e_1_3_3_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1985.tb03692.x"
    },
    {
      "key": "e_1_3_3_25_2",
      "first-page": "295",
      "volume": "6",
      "author": "Klein J",
      "year": "1986",
      "unstructured": "J Klein, F Figueroa Crit Rev Immunol 6, 295\u2013386 (1986).",
      "journal-title": "Crit Rev Immunol"
    },
    {
      "key": "e_1_3_3_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/122.3.681"
    },
    {
      "key": "e_1_3_3_27_2",
      "first-page": "491",
      "volume": "7",
      "author": "Hughes A L",
      "year": "1990",
      "unstructured": "A L Hughes, M Nei Mol Biol Evol 7, 491\u2013514 (1990).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_28_2",
      "volume-title": "Natural History of the Major Histocompatibility Complex",
      "author": "Klein J",
      "year": "1986",
      "unstructured": "J Klein Natural History of the Major Histocompatibility Complex (Wiley, New York, 1986)."
    },
    {
      "key": "e_1_3_3_29_2",
      "volume-title": "Evolutionary Genetics from Molecules to Morphology",
      "author": "Hedrick P W",
      "year": "1997",
      "unstructured": "P W Hedrick, T J Kim Evolutionary Genetics from Molecules to Morphology, eds R S Singh, C K Krimbas (Cambridge Univ. Press, New York, , in press. (1997)."
    },
    {
      "key": "e_1_3_3_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/335167a0"
    },
    {
      "key": "e_1_3_3_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1098/rstb.1994.0115"
    },
    {
      "key": "e_1_3_3_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/357329a0"
    },
    {
      "key": "e_1_3_3_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF02602779"
    },
    {
      "key": "e_1_3_3_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/310650a0"
    },
    {
      "key": "e_1_3_3_35_2",
      "volume-title": "mega: Molecular Evolutionary Genetic Analysis",
      "author": "Kumar S",
      "year": "1993",
      "unstructured": "S Kumar, K Tamura, M Nei mega: Molecular Evolutionary Genetic Analysis (Pennsylvania State Univ., University Park, 1993)."
    },
    {
      "key": "e_1_3_3_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.iy.08.040190.000323"
    },
    {
      "key": "e_1_3_3_37_2",
      "doi-asserted-by": "crossref",
      "first-page": "3619",
      "DOI": "10.4049/jimmunol.144.9.3619",
      "volume": "144",
      "author": "Zemmour J",
      "year": "1990",
      "unstructured": "J Zemmour, B H Koller, P D Ennis, D E Geraghty, D A Lawlor, H T Orr, P Parham J Immunol 144, 3619\u20133629 (1990).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_3_38_2",
      "doi-asserted-by": "crossref",
      "first-page": "1947",
      "DOI": "10.4049/jimmunol.149.6.1947",
      "volume": "149",
      "author": "Geraghty D E",
      "year": "1992",
      "unstructured": "D E Geraghty, B H Koller, J Pei, J A Hansen J Immunol 149, 1947\u20131957 (1992).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_3_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.genet.30.1.371"
    },
    {
      "key": "e_1_3_3_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00216696"
    },
    {
      "key": "e_1_3_3_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00176441"
    },
    {
      "key": "e_1_3_3_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/115.1.161"
    },
    {
      "key": "e_1_3_3_43_2",
      "doi-asserted-by": "crossref",
      "first-page": "2547",
      "DOI": "10.4049/jimmunol.148.8.2547",
      "volume": "148",
      "author": "Chen Z W",
      "year": "1992",
      "unstructured": "Z W Chen, S N McAdam, A L Hughes, A L Dogon, N L Letvin, D I Watkins J Immunol 148, 2547\u20132554 (1992).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_3_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/381226a0"
    },
    {
      "key": "e_1_3_3_45_2",
      "first-page": "753",
      "volume": "8",
      "author": "Schneider S",
      "year": "1991",
      "unstructured": "S Schneider, V Vincek, H Tichy, F Figueroa, J Klein Mol Biol Evol 8, 753\u2013766 (1991).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_46_2",
      "first-page": "441",
      "volume": "12",
      "author": "Slade R W",
      "year": "1995",
      "unstructured": "R W Slade, W E Mayer Mol Biol Evol 12, 441\u2013450 (1995).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_47_2",
      "first-page": "447",
      "volume": "6",
      "author": "Tanaka T",
      "year": "1989",
      "unstructured": "T Tanaka, M Nei Mol Biol Evol 6, 447\u2013459 (1989).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0888-7543(95)80201-V"
    },
    {
      "key": "e_1_3_3_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI118198"
    },
    {
      "key": "e_1_3_3_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/B978-012053640-5/50011-2"
    },
    {
      "key": "e_1_3_3_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng0694-162"
    },
    {
      "key": "e_1_3_3_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng0193-88"
    },
    {
      "key": "e_1_3_3_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/B978-012053640-5/50010-0"
    },
    {
      "key": "e_1_3_3_54_2",
      "volume-title": "v base Sequence Directory",
      "author": "Tomlinson I M",
      "year": "1996",
      "unstructured": "I M Tomlinson, S C Williams, O Ignatovich, S J Corbertt, G Winter v base Sequence Directory (MRC Centre for Protein Engineering, Cambridge, U.K., 1996)."
    },
    {
      "key": "e_1_3_3_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/intimm/2.1.41"
    },
    {
      "key": "e_1_3_3_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.1996.0636"
    },
    {
      "key": "e_1_3_3_57_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0923-2494(96)87226-9"
    },
    {
      "key": "e_1_3_3_58_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF00188170"
    },
    {
      "key": "e_1_3_3_59_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(89)90879-9"
    },
    {
      "key": "e_1_3_3_60_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/B978-012053640-5/50016-1"
    },
    {
      "key": "e_1_3_3_61_2",
      "doi-asserted-by": "crossref",
      "first-page": "2163",
      "DOI": "10.4049/jimmunol.156.6.2163",
      "volume": "156",
      "author": "Dufour V",
      "year": "1996",
      "unstructured": "V Dufour, S Malinge, N Francois J Immunol 156, 2163\u20132170 (1996).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_3_62_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/oxfordjournals.molbev.a040194"
    },
    {
      "key": "e_1_3_3_63_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.iy.09.040191.001251"
    },
    {
      "key": "e_1_3_3_64_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/302575a0"
    },
    {
      "key": "e_1_3_3_65_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(80)90426-2"
    },
    {
      "key": "e_1_3_3_66_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1985.tb04013.x"
    },
    {
      "key": "e_1_3_3_67_2",
      "first-page": "247",
      "volume": "12",
      "author": "Hughes A L",
      "year": "1995",
      "unstructured": "A L Hughes Mol Biol Evol 12, 247\u2013258 (1995).",
      "journal-title": "Mol Biol Evol"
    },
    {
      "key": "e_1_3_3_68_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/221040a0"
    },
    {
      "key": "e_1_3_3_69_2",
      "first-page": "137",
      "volume": "8",
      "author": "Klein J",
      "year": "1993",
      "unstructured": "J Klein, H Ono, D Klein, C O\u2019hUigin Prog Immunol 8, 137\u2013143 (1993).",
      "journal-title": "Prog Immunol"
    },
    {
      "key": "e_1_3_3_70_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0378-1119(95)00627-3"
    },
    {
      "key": "e_1_3_3_71_2",
      "doi-asserted-by": "crossref",
      "first-page": "5618",
      "DOI": "10.4049/jimmunol.153.12.5618",
      "volume": "153",
      "author": "Sun J",
      "year": "1994",
      "unstructured": "J Sun, I Kacskovics, W R Brown, J E Butler J Immunol 153, 5618\u20135627 (1994).",
      "journal-title": "J Immunol"
    },
    {
      "key": "e_1_3_3_72_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1749-6632.1995.tb55845.x"
    },
    {
      "key": "e_1_3_3_73_2",
      "doi-asserted-by": "crossref",
      "first-page": "2027",
      "DOI": "10.4049/jimmunol.146.6.2027",
      "volume": "146",
      "author": "Roux K H",
      "year": "1991",
      "unstructured": "K H Roux, P Dhanarajan, V Gottschalk, W T McCormack, R W Renshaw J Immunol 146, 2027\u20132036 (1991).",
      "journal-title": "J Immunol"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.94.15.7799",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        4,
        22
      ]
    ],
    "date-time": "2023-04-22T12:05:59Z",
    "timestamp": 1682165159000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.94.15.7799"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1997,
        7,
        22
      ]
    ]
  },
  "references-count": 73,
  "journal-issue": {
    "issue": "15",
    "published-print": {
      "date-parts": [
        [
          1997,
          7,
          22
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.94.15.7799"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.94.15.7799",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        1997,
        7,
        22
      ]
    ]
  },
  "assertion": [
    {
      "value": "1997-07-22",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}