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RESEARCH INTERESTS
Genetics, molecular biology, microbiology
Ciliate macronuclear development
Transposon biology
Chromosome elimination and other 'selfish' genetic phenomena
PUBLICATIONS
Poster
Development of a somatic 'gene readout' organelle, the macronucleus
"Selfish genes" - such as transposons, meiotic drive genes and -
potentially, imprint-instructed genes - succeed with only secondary regard
for the fitness of the organism carrying them. We study a family of
notably "considerate," "get-out-of-the-way" transposons in the ciliated
protozoan Oxytricha. In collaboration with Jon Seger, I also
explore the evolutionary consequences of conflicts of interest between
maternally and paternally inherited genes, as reflected by paternal genome
elimination in male scale insects, and paternal X chromosome inactivation
in mammals.
A ciliate develops separate germline and somatic nuclei, the micronucleus
and the macronucleus ("MAC"), from mitotic daughters of the zygotic
nucleus. Genes are expressed only from the somatic nucleus. As the MAC
develops it undergoes massive rearrangements -- chromosome breakage +
telomere formation, amplification, precise excision of germline-limited
segments. These rearrangements have attracted attention as possible novel
forms of gene regulation, as in immune cells, but we believe that the
rearrangements are more plausibly the result of many selfish DNAs that
have invaded the ciliate germline.
TBE transposons have been highly successful in Oxytricha (~2000
TBE1s in the micronucleus), apparently because they are quantitatively and
precisely excised from the developing somatic nucleus. As a result, TBE1
copies can insert with relative abandon in the germline genome, without
compromising host fitness, because the resulting mutations are not
expressed. TBE1s are precisely excised as 4.1kbp circles carrying one
copy of the original target duplication, leaving the target "healed" in
the mature macronuclear genes, as if the elements were never there.
TBE1s carry three genes, for transposase, and for two other proteins of no
known function. The function but not the sequences these genes has been
conserved in most of the ~2000 members, a very striking but unexplained
phenomenon, as existing theory does not predict that genes of such
transposons in eukaryotes should be maintained by purifying selection. A
dynamic mathematical model for the evolution of eukaryotic transposons has
been developed by David Witherspoon, a graduate student in my lab. This
model suggests that "trait-group selection" could maintain transposases
under conditions that seem plausible for many ciliates and other
eukaryotes. For example, there are conserved transposases on the Tec
elements of another ciliate species.
In many scale insects (Coccoidea, or "coccids"), the maternal and paternal
chromosome sets are differentially imprinted. The paternal set ("P-set")
is not passed on in sperm. We believe this is caused by a novel mutation
only expressed from the M-set; a powerful selection exists for it, since
it enjoys a 2x increase in fitness, being transmitted through males
without the usual 2x "cost of meiosis." A powerful selection also exists
for P-set counter-mutations. We postulate that a long series of P-vs.-M
mutational "battles" in the past ~300 million years has produced the known
variety of P-set exclusion systems: early heterochromatic inactivation
with meiotic elimination, and male parthenogenic development (from egg
with only M-set). In some coccids, the P-set evades elimination, possibly
by lacking an imprint, or by mimicking the maternal imprint. CpG
methylation likely is involved in coccid imprinting, and we will study
methylation patterns in these putative "escapee" coccids.
Selected publications
Witherspoon DJ. Selection on transposons by horizontal transfer or group
selection: Evidence from Tam3 of Antirrhinum majus. Submitted.
Witherspoon D, Doak TG, Jahn CL, Herrick G. Selection on the genes of
Tec1 and Tec2 transposons of Euplotes crassus: evolutionary
appearance of a programmed frame shift in a Tec2 gene encoding a
tyrosine-type, site-specific recombinase. Submitted.
Witherspoon DJ (1999) Selective constraints on P-element evolution. Mol.
Biol. Evol. 16:472-478.
Herrick G, Seger J (1999) Imprinting and paternal genome elimination in
insects. In Genomic Imprinting: An Interdisciplinary Approach (ed
R. Ohlsson). Springer-Verlag.
Witherspoon D, Doak TG, Williams KR, Seger J, Herrick G (1997) Selection
on the protein-coding genes of the TBE1 family of transposable elements in
the ciliates Oxytricha fallax and O. trifallax. Mol. Biol.
Evol. 14:696-706.
Klobutcher LA, Herrick, G (1997) Developmental genome reorganization in
ciliated protozoa: the transposon link. Prog. Nucleic Acid Res. and Mol.
Biol. 56:1-62.
Seegmiller A, Williams KR, and Herrick, G (1997) Two two-gene
macronuclear chromosomes of the hypotrichous ciliates Oxytricha
fallax and O. trifallax generated by alternative processing of
the 81 locus. Dev. Genet. 20: 438-357.
Doak TG, Doerder FP, Jahn CJ, Herrick G (1994) A family of transposase
genes in transposons found in prokaryotes, multicellular eukaryotes and
ciliated protozoans. Proc. Natl. Acad. Sci. USA 91:942-946.
Williams K, Doak TG, Herrick G (1993) Precise excision of Oxytricha
trifallax telomere-bearing elements and formation of circles closed by
a copy of the flanking target duplication. EMBO J. 12:4593-4601.
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