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Genetics
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Research Interests
My research
is motivated by a desire to answer one of the fundamental questions in evolutionary
biology – the genetic changes that underlie phenotypic differences between
species. Both genetic and phenotypic changes between closely related species
have been well documented, but very little about the connections between the
two is known. One way to understand the genetic changes of species differentiation
is to study the genetics of individual traits that contribute to any form of
reproductive isolation, such as habitat shift, premating isolation, etc., between
closely related species. The main goal of my research is to make a connection
between genotypic and phenotypic changes that occur during species divergence,
and my basic approach is to use genetic tools to study those phenotypic differences.
My current projects and related works are summarized as follows:
A.
Molecular genetics and evolution of reproductive isolation
Since Dobzhansky’s first study of reproductive isolation, much effort has
been put into genetic studies of species differences. Several genetic elements,
especially those involved in hybrid male sterility between D. simulans
and D. mauritiana, have been precisely mapped (see a recent review by
Wu and Hollocher, 1998) but none of them had been characterized at molecular
level. Among those hybrid male sterility elements, a strong genetic factor,
Odysseus (Ods) (Perez
et al., 1993), appeared most promising for molecular cloning. Since 1996,
I have been working on this gene while carrying out other projects. In early
1998, I showed that a paired-type homeobox gene (OdsH, homeobox at Ods
site) is the Ods element (Ting
et al., 1998). This may be the first gene of postmating reproductive isolation
characterized at the molecular level since Dobzhansky’s pioneering work.
Because most homeobox genes play an important role in gene regulation, it is
likely that OdsH also acts as a transcription factor. If so, the result
supports the hypothesis that regulatory changes are crucial in speciation. I
have subsequently found that this gene is a duplicated copy of another conservative
homeobox gene in Drosophila. One of the consequences of gene duplication
may be rapid functional divergence, leading to speciation.
(1) Molecular cloning of Odysseus
I first mapped the Ods locus of hybrid male sterility to an 8kb genomic
fragment by positional cloning, and then further refined the mapping to less
than 3 kb. From the DNA sequence analysis, I found that this 3kb region contains
part of a paired-type homeobox gene and named it OdsH. The OdsH is
almost certainly the genetic locus of Ods although the final proof is
still in progress.
OdsH has undergone rapid evolution even between very closely related species.
In the past half million years, this homeodomain has experienced more amino
acid substitutions than in the preceding 700 million years and, during this
period, has also evolved faster than other parts of the protein or even the
introns. It was inevitable to conclude that such a rapid sequence divergence
is driven by positive selection and the reproductive isolation is a consequence
of this rapid divergence (Ting
et al., 1998).
(2)
The phylogenetic history of Odysseus
Molecular differentiation between races or closely related species is often
incongruent with the reproductive divergence of the taxa of interest. Shared
ancient polymorphism and/or introgression during secondary contact may be responsible
for the incongruence. At loci contributing to speciation, these two complications
should be minimized; hence, their variation may more faithfully reflect the
history of the species’ reproductive differentiation. I analyzed DNA polymorphism
at the Odysseus (OdsH) locus of hybrid sterility between Drosophila
mauritiana and D. simulans and were able to verify such a prediction.
Interestingly, DNA variation only a short distance away (1.8 kb) appears not
to be influenced by the forces that shape the recent evolution of the OdsH
coding region. This locus may thus represent a test case of inferring phylogeny
of very closely related species. (Ting
et al., 2000)
(3)
Gene duplication leading to the formation of OdsH (work in progress)
Recently, more precise genetic mapping has shown that another homeobox gene,
unc-4, is located less than 50 kb from OdsH. Both OdsH
and unc-4 in Drosophila belong to the paired-type homeodomain
protein family and the intron/exon junctions of these two genes are identical.
Phylogenetic analysis shows that these two genes probably arose through recent
gene duplication and OdsH in all species has evolved at a very high rate.
In contrast, the amino acid sequences of unc-4 are nearly identical between
D. melanogaster and D. tessieri. This sequence conservation indicates
strong selective constraint on unc-4 in the Drosophila lineage.
The sequence divergence between OdsH and unc-4 could have been
initiated by relaxation of selection right after the duplication event. Subsequently,
a new male germline function acquired by OdsH has led to its rapid evolution.
Hybrid male sterility could be one of the consequences of these events.
B. Genetic
analysis of sexual isolation
In order to understand the genetic architecture of species divergence, the second
part of my thesis focused on the genetic analysis of premating isolation in
D. melanogaster. D. melanogaster females from Zimbabwe and nearby
regions (the Z-type) would mate only with males of the same geographical origin
but not with the regular D. melanogaster males (the M-type, which is
cosmopolitan in distribution). Variations in mating preference among natural
isolates of D. melanogaster have been measured. Through a survey of four
populations in southern Africa and five cosmopolitan lines, we observed extensive
genetic variation in mating preference as well as positive correlation between
sexes. The populations are highly differentiated and represent various stages
of evolution between the African and the cosmopolitan type of sexual behaviors.
The genetic variations in these sexual characters coupled with their pattern
of evolution have implications for models of speciation by sexual selection.
The genes for the behaviors are mapped to all three major chromosomes with the
same ranking and comparable magnitude of effects for both sexes: III > II
>> X Ž 0 (III, II and X designate the effects of the three chromosomes).
Whole-chromosome effects for Z-maleness appear nearly additively and show little
dominance. Various intermediate genotypes can be arranged on a linear additive
scale according to their Z-maleness. Such a continuous, linear male trait may
indicate that the effects of multiple cues interact additively in male sexual
behavior. One the other hand, chromosomal effects for Z-femaleness are more
complex - epistatic interactions are evident in certain genetic backgrounds
and Z-dominance, though incomplete, can often be seen.
The chromosomal effects are strong enough to allow further characterization
at the genic level. At least four different chromosomal segments responsible
for either male or female behavior are identified on the third chromosome alone.
Since we mapped both male genes and female genes in different regions of the
chromosome, it is possible to further characterize the genetic interactions
between them.
In summary, the work on both premating and postmating reproductive isolation demonstrate the importance of bridging the genotypic and the phenotypic changes in species divergence. One can expect to have much better understanding of species differences as the molecular characterization of reproductive isolation progresses.
Ting, C.-T., S. C. Tsaur, M.-L. Wu and C.-I Wu 1998 A rapidly evolving homeobox at the site of a hybrid sterility gene. Science 282:1501-1504. MEDLINE
Tsaur, S. C., C.-T. Ting and C. -I Wu 1998 Positive selection driving the evolution of a gene of male reproduction, Acp26Aa of Drosophila: II. Divergence vs. polymorphism. Mol. Biol. Evol. 15:1040-1046. MEDLINE
Hollocher, H., C.-T. Ting, M.-L Wu, and C. -I Wu 1997 Incipient speciation by sexual isolation in Drosophila melanogaster: extensive genetic divergence without reinforcement. Genetics 147:1191-1201. MEDLINE
Hollocher, H., C.-T. Ting, F. Pollack, and C. -I Wu 1997 Incipient speciation by sexual isolation in Drosophila melanogaster: variation in mating preference and correlation between sexes. Evolution 51(4):1175-1181.