Convergent evolution of apolipoprotein(a) in primates and hedgehog

Richard M. Lawn, Karen Schwartz, L. Patthy

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Apolipoprotein(a) [apo(a)] is the distinguishing protein component of lipoprotein(a), a major inherited risk factor for atherosclerosis. Human apo(a) is homologous to plasminogen. It contains from 15 to 50 repeated domains closely related to plasminogen kringle four, plus single kringle five-like and inactive protease-like domains. This expressed gene is confined to a subset of primates. Although most mammals lack apo(a), hedgehogs produce an apo(a)-like protein composed of highly repeated copies of a plasminogen kringle three-like domain, with complete absence of protease domain sequences. Both human and hedge-hog apo(a)-like proteins form covalently linked lipoprotein particles that can bind to fibrin and other substrates shared with plasminogen. DNA sequence comparisons and phylogenetic analysis indicate that the human type of apo(a) evolved from a duplicated plasminogen gene during recent primate evolution. In contrast, the kringle three-based type of apo(a) evolved from an independent duplication of the plasminogen gene approximately 80 million years ago. In a type of convergent evolution, the plasminogen gene has been independently remodeled twice during mammalian evolution to produce similar forms of apo(o) in two widely divergent groups of species.

Original languageEnglish
Pages (from-to)11992-11997
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number22
DOIs
Publication statusPublished - Oct 28 1997

Fingerprint

Apoprotein(a)
Hedgehogs
Plasminogen
Primates
Kringles
Peptide Hydrolases
Genes
Lipoprotein(a)
Proteins
Gene Duplication
Fibrin
Lipoproteins
Mammals
Atherosclerosis

Keywords

  • Gene duplication
  • Lipoprotein(a)
  • Plasminogen

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Convergent evolution of apolipoprotein(a) in primates and hedgehog. / Lawn, Richard M.; Schwartz, Karen; Patthy, L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 22, 28.10.1997, p. 11992-11997.

Research output: Contribution to journalArticle

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