Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Jul 1977; 86(3): 623–644.
PMCID: PMC1213699

Phylogenies Constrained by the Crossover Process as Illustrated by Human Hemoglobins and a Thirteen-Cycle, Eleven-Amino-Acid Repeat in Human Apolipoprotein a-I


Examination of human apolipoprotein A-I revealed a segment of eleven amino acids that repeated itself 13 times in succession without any additional intervening amino acids between the beginning of the repeats (amino acid 93) and their end at the carboxyl terminus of the sequence. The segments are not identical, but the pattern of their physical and chemical properties is highly conserved. The pattern is shown to be suitable to the formation of alpha helices with an amphipathic character consistent with the formation of a micellar structure, a process entirely appropriate to the protein's known function in the blood stream as a lipid carrier. The simplest hypothesis to account for repeated segments is a series of unequal crossovers. But such a series implies that some segments are more closely related to each other than they are to others, that is, they have a "phylogenetic" relationship. It is shown that only a small fraction of all possible phylogenies are consistent with a set of segments arising by simple unequal crossing over. Nevertheless, it is shown that the apolipoprotein A-I segments are readily interpretable as the result of simple unequal crossing over. Moreover, the crossover constraint applies with as much force to segments larger than a gene as to segments within a gene, and this is shown to require that the human gamma (Gly) hemoglobin gene lie to the left, rather than to the right, of the other non-alpha human hemoglobin genes, a conclusion for which there is no direct genetic evidence currently available.

Full Text

The Full Text of this article is available as a PDF (2.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baker HN, Gotto AM, Jr, Jackson RL. The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). II. The amino acid sequence and alignment of cyanogen bromide fragments IV, III, and I. J Biol Chem. 1975 Apr 10;250(7):2725–2738. [PubMed]
  • BRAUNITZER G, GEHRING-MUELLER R, HILSCHMANN N, HILSE K, HOBOM G, RUDLOFF V, WITTMANN-LIEBOLD B. [The structure of normal adult human hemoglobins]. Hoppe Seylers Z Physiol Chem. 1961 Sep 20;325:283–286. [PubMed]
  • Brewer HB, Jr, Lux SE, Ronan R, John KM. Amino acid sequence of human apoLp-Gln-II (apoA-II), an apolipoprotein isolated from the high-density lipoprotein complex. Proc Natl Acad Sci U S A. 1972 May;69(5):1304–1308. [PMC free article] [PubMed]
  • HILL RJ, KONIGSBERG W. The structure of human hemoglobin. IV. The chymotryptic digestion of the alpha chain of human hemoglobin. J Biol Chem. 1962 Oct;237:3151–3156. [PubMed]
  • Scanu A, Hirz R. On the structure of human serum high-density lipoprotein: studies by the technique of circular dichroism. Proc Natl Acad Sci U S A. 1968 Mar;59(3):890–894. [PMC free article] [PubMed]
  • Schiffer M, Edmundson AB. Use of helical wheels to represent the structures of proteins and to identify segments with helical potential. Biophys J. 1967 Mar;7(2):121–135. [PMC free article] [PubMed]
  • Schroeder WA, Huisman TH, Shelton JR, Shelton JB, Kleihauer EF, Dozy AM, Robberson B. Evidence for multiple structural genes for the gamma chain of human fetal hemoglobin. Proc Natl Acad Sci U S A. 1968 Jun;60(2):537–544. [PMC free article] [PubMed]
  • Shen BW, Scanu AM, Kézdy FJ. Structure of human serum lipoproteins inferred from compositional analysis. Proc Natl Acad Sci U S A. 1977 Mar;74(3):837–841. [PMC free article] [PubMed]
  • Weatherall DJ, Clegg JB. Molecular genetics of human hemoglobin. Annu Rev Genet. 1976;10:157–178. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...