Detecting and characterizing gene conversions between multigene family members.

We used a variety of methods to detect known gene conversions in the actin gene families of five angiosperm species, the beta-globin gene families of two primate species, and the Zfx/Zfy gene families of seven mammalian species. Our goal was to devise a working strategy which would allow the analysis of the members of a multigene family in order to determine whether there had been gene conversions between its members, identify the genes involved in the gene conversions, establish the lengths of the converted regions, and determine the polarities of the gene conversions. We show that three phylogenetic methods and the homoplasy test of Maynard Smith and Smith perform relatively poorly on our data sets because the sequences we analyzed had large levels of multiple substitutions. The method of Sawyer, the compatibility method of Jakobsen and Easteal, the partition matrix method of Jakobsen, Wilson, and Easteal, and the co-double method of Balding, Nichols, and Hunt can be used to identify the genes which have been involved in gene conversions. The co-double method is more powerful than other methods but requires orthologous sequences from related species. Compatibility, phylogenetic, and nucleotide substitution distribution statistics methods can be used to identify the location of the converted region(s). Site-by-site compatibility analyses can also be used to identify the direction of the conversion event(s). Combinations of these methods can therefore be used to establish the presence, locations, and polarities of gene conversions between multigene family members.

[1]  M. Menotti-Raymond,et al.  Characterization of the structure and evolution of the Adh region of Drosophila hydei. , 1991, Genetics.

[2]  R. Mortimer,et al.  Recombination in yeast. , 1971, Annual review of genetics.

[3]  J. Stephens,et al.  Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion. , 1985, Molecular biology and evolution.

[4]  J. Vandekerckhove,et al.  Chordate muscle actins differ distinctly from invertebrate muscle actins. The evolution of the different vertebrate muscle actins. , 1984, Journal of molecular biology.

[5]  A. Hughes,et al.  Origin and evolution of HLA class I pseudogenes. , 1995, Molecular biology and evolution.

[6]  M. Goodman,et al.  Orangutan fetal globin genes. Nucleotide sequence reveal multiple gene conversions during hominid phylogeny. , 1987, The Journal of biological chemistry.

[7]  G. McGuire,et al.  A graphical method for detecting recombination in phylogenetic data sets. , 1997, Molecular biology and evolution.

[8]  S. Sawyer.  Statistical tests for detecting gene conversion. , 1989, Molecular biology and evolution.

[9]  S. Holm.  A Simple Sequentially Rejective Multiple Test Procedure , 1979 .

[10]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[11]  G. Weiller.  Phylogenetic profiles: a graphical method for detecting genetic recombinations in homologous sequences. , 1998, Molecular biology and evolution.

[12]  D. Balding,et al.  Detecting gene conversion: primate visual pigment genes , 1992, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[13]  G. Drouin,et al.  Phylogeny and substitution rates of angiosperm actin genes. , 1996, Molecular biology and evolution.

[14]  Ann E. Blechl,et al.  Human fetal g γ- and A γ-globin genes: Complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes , 1980, Cell.

[15]  E. Holmes,et al.  A likelihood method for the detection of selection and recombination using nucleotide sequences. , 1997, Molecular biology and evolution.

[16]  P. H. A. Sneath,et al.  Detecting Evolutionary Incompatibilities From Protein Sequences , 1975 .

[17]  B. Gaut,et al.  Molecular evolution of the Adh1 locus in the genus Zea. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. McDowell,et al.  Structure and evolution of the actin gene family in Arabidopsis thaliana. , 1996, Genetics.

[19]  Wen-Hsiung Li,et al.  Fundamentals of molecular evolution , 1990 .

[20]  D. Bhattacharya,et al.  The origin and evolution of green algal and plant actins. , 1999, Molecular biology and evolution.

[21]  M. Goodman,et al.  Phylogenetic scanning: a computer-assisted algorithm for mapping gene conversions and other recombinational events , 1991, Comput. Appl. Biosci..

[22]  Simon Easteal,et al.  A program for calculating and displaying compatibility matrices as an aid in determining reticulate evolution in molecular sequences , 1996, Comput. Appl. Biosci..

[23]  E. L. Simons,et al.  Tarsius delta- and beta-globin genes: conversions, evolution, and systematic implications. , 1989, The Journal of biological chemistry.

[24]  T. Ohta,et al.  Gene conversion generates hypervariability at the variable regions of kallikreins and their inhibitors. , 1992, Molecular phylogenetics and evolution.

[25]  M. Goodman,et al.  Fetal recruitment of anthropoid γ-globin genes: Findings from phylogenetic analyses involving the 5′-flanking sequences of the ψγ1 globin gene of spider monkey Ateles geoffroyi , 1992 .

[26]  K. Rice,et al.  Molecular evolution of the small subunit of ribulose bisphosphate carboxylase: nucleotide substitution and gene conversion. , 1989, Genetics.

[27]  S. Easteal,et al.  The partition matrix: exploring variable phylogenetic signals along nucleotide sequence alignments. , 1997, Molecular biology and evolution.

[28]  E. Betrán,et al.  The estimation of the number and the length distribution of gene conversion tracts from population DNA sequence data. , 1997, Genetics.