Nothing in biology makes sense except in the light of evolution.

-Theodosius Dobzhansky

Nothing in evolution makes sense except in the light of biology,

and nothing in biology makes sense except in a systemic view.

-Xianfa Xie

The goal of my scientific research is to integrate different fields of biology and other related sciences (particularly chemistry, geology, and physics) to reach a holistic understanding of biology and evolution, and further use that knowledge to address important problems facing the human society and the natural world today, including health, agriculture, environmental protection, and biodiversity conservation.

My initial research focus was in evolutionary biology, using a combination of DNA sequence and ecological data and employing phylogenetics, population genetics, and statistical methods to study the history and mechanisms of evolution. Always wanting to know exactly how things work, I studied the algorithms and computational processes underlying the many existing methods in evolutionary analysis, only to realize the inadequacies and uncertainties of many of them, which prompted me to develop new methods or modifications for improvement. Meanwhile, I believe one cannot really understand how evolution occurs without understanding the molecular mechanisms of inheritance, development, and the effects of environment, which pushs me to seek insights from all the other fields of biology. Furthermore, I once strongly felt that biological research based on single genes or sporadically discovered pairwise interactions between molecules could not provide a global view and the real picutre of biological processes, which motivates me to pursue genomic and systems biological studies.

So my current research is highly interdisciplinary. I am trying to understand important biological, medical, agronomic, and evolutionary questions by integrating all fields of biology and related sciences, and by using a combination of computational methods and large-scale biological datasets.

The following is a list and description of my research experience and interests. I still have many of the interests today, while studying them with different priorities.

 

I. SPECIATION


How new species have evolved is the central question in evolutionary biology and was once called by Charles Darwin as “the mystery of mysteries”. Two opposing views have been proposed to explain the origin of new species (i.e., speciation), one requiring geographic isolation (allopatric speciation) and the other not (sympatric speciation). The maggot fly Rhagoletis pomonella has been a textbook example for sympatric speciation, as historical records showed that this species shifted from its ancestral host plant hawthorns to newly introduced apples about 150 years ago in the Hudson Valley area in the United States. The whole species complex, including not only R. pomonella but also several other species, was also proposed to have evolved through shifting to new host plants in sympatry (i.e., within the same geographic range).

 

Rhagoletis pomonella species complex

To test this hypothesis, I carried out a large-scale evolutionary study using the DNA sequence of 15 genes distributed across the fly's nuclear genome as well as a mitochondrial gene (CO II) from a sample of 15 populations representing all the major taxon groups, including previously unstudied Mexican R. pomonella-like fly populations. This constituted the largest molecular dataset that has ever generated for this species group.

Evolutionary analyses including phylogenetic reconstruction and population genetic studies yielded a series of significant findings regarding the evolution of new species. My study revealed that chromosomal inversiion and ecological differentiation are two important mechanisms for speciation. Most surprisingly, it revealed allopatric speciation by geographic isolation has played a more important role in the evolution of this species complex and cast into question the R. pomonella species as a textbook model system for sympatric speciation .


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II. THE EVOLUTIONARY GENOMICS OF RICE DOMESTICATION

 

As the staple food for half of the world population, rice is arguably the most important crop plant. The domestication of rice and other plants and animals also helped Darwin to formulate his theory of natural selection. The domesticated rice is widely different from the wild rice species. Besides, there exists tremendous genetic and ecological variation even among domesticated rice varieties. Using large-scale DNA sequence datasets from both genome wide and targeted regions, I studied the evolutionary history of Asian domesticated rice and whether different rice varieties were domesticated on the same genetic basis.

 

rice fieldrice anatomy

 

Through a comprehensive set of phylogenetic and population genetic analyses, in which I developed new methods to address the various problems encountered by other similar studies, my study revealed that each domesticated rice variety has a distinct origin and different rice varieties were domesticated on different genetic basis for the same agriculturally important traits.


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III. INTEGRATIVE ANALYSIS OF RICE GENOMICS, TRANSCRIPTOMICS, AND EPIGENOMICS

 

To better understand the differentiation between the domesticated and wild rice requires comparative studies at the genomic (looking at DNA sequence), transcriptomic (examining gene expression), and epigenomic (studying the mechanisms regulating gene expression) levels. In collaboration with colleagues, we generated such data using next-generation sequencing technologies, particularly revealing the rice epigenome for the first time.

Through a detailed analysis of these huge datasets at all three levels, by using high-performance computing facilities and methods, we found the wild rice and domesticated rice varieties differ not only in DNA sequence but also in gene expression and DNA methylation across the genomes. By correlating the data at genomic, transcriptomic, and epigenomic levels, our study revealed new molecular mechanisms underlying gene expression regulation and genomic evolution. Besides, we identified candidate genes that showed significant gene expressional changes associated with DNA methylation difference, which may have been involved in the differentiation of domesticated rice from the its wild progenitor.


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IV. EPIGENETICS AND TRANSPOSABLE ELEMENTS


Transposable elements (TEs) and other repeat sequences were generally considered as junks by early geneticists or nuisances in today’s genomic sequencing projects. However, they occupy a great proportion of eukaryotic genomes and are often the major genomic component distinguishing closely related organisms. I am interested in the various, ofen significant, roles played by transposable elements and sequence repeats in genomic evolution.

Epigenetics is a new area that grows out of the traditional field of genetics dominated by DNA sequence study. However, epigenetic changes, i.e., modifications (e.g. methylation and acetylation) of DNA or chromatin without changing the primary DNA sequence, are prevalent in plants, fungi, and animals and could result in significant phenotypic divergence.

The above two areas have just begun to be connected in some studies on plants. Once connected, however, they demonstrate extraordinary power in understanding some of the most fundamental problems in evolutionary biology, ecology, and biology in general.


I am interested in studying how the epigenetic regulation system of TEs and sequence repeats incorporates environmental stimuli to create functional novelties of ecological and evolutionary significance. I am also interested in examining these questions in relation to agriculture and human health, for the latter of which I am particularly interested in how the diet and chemical pollutants from the environment could alter the epigenetic states of human genome and cause diseases like cancer.


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V. MOLECULAR EVOLUTION OF YEAST SOCIAL ADHESINS

 

beer yeastbeer chemistrybeer bread

 

Currently I am studying how the genes encoding proteins involved in cell-cell interactions have evolved in yeast, particularly in the Brewer’s or Baker’s yeast, Saccharomyces cerevisiae, and its most closely related species, S. paradoxus. These “social” genes, which include those involved in mate recognition (sexual reproduction), flocculation (precipitation in fermentation), biofilm formation, pathogen-host attachment, are of both theoretical significance (to study the genetic basis of speciation in yeast) and practical importance (to brewing industry, medical treatment, and environmental protection). Using comparative genomic and evolutionary bioinformatic methods, my study has revealed several particular patterns in the evolution of these “social” genes, particularly the sexual adhesins.


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VI. BIOINFORMATICS FOR POPULATION GENETICS, PHYLOGENOMICS, AND SYSTEMS BIOLOGY


Through my research in evolutionary and population genetics, I have come to realize the gross inadequencies of the many methods that are commonly used in these fields to purportedly address some important biological or evolutionary questions, like recombination and selection. I am interested in reassessing these methods and develop biologically more realistic ones.

As the genomic data become increasingly available, it is becoming possible to construct phylogeny based on whole-genome data. The latter offers several advantages over traditional approach based on just one or a few loci. However, several important theoretical and technical problems have to be solved before phylogenomic analysis can be put into good use. I am interested in addressing these problems and developing methods for phylogenomic construction.

The newly emerged field of systems biology, though still varying significantly in research topics and methods, holds great promises to address biological questions using a comprehensive approach. To realize such potential would require developing biologically more realistic models and integrating biologically more relevant data in a better way, which is the purpose of my study.


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VI. NEW EVOLUTIONARY SYNTHESIS AND INTEGRATIVE BIOLOGY


The famous saying of the evolutionary biologist Dobzhansky that "Nothing in biology makes sense except in the light of evolution" is only half true. In my opinion, nothing in evolution makes sense except in the light of biology. Traditionally, the field of evolutionary biology has almost exclusively relied on naturalistic observations, mathematical modeling, and unfortunately a simplistic understanding of biology. Over the last decade or so, the limitation of the current working paradigm, the ambiguity of some key concepts, and the falsehood of many conventional “wisdoms” in the field have become painfully clear to me, which propells me to reach for a comprehensive new understanding of biological evolution by integrating information at molecular, genomic, and population levels and perspectives from genetics, epigenetics, structural biology, development, and ecology, together with some critical theoretical thinking.

 

integrate biology for evolution

 

 

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VII. THE HISTORY, PHILOSOPHY, AND SOCIOLOGY OF SCIENCE


Science is supposed to be logical, objective, and universal. In reality, just like many other ideas, science is often a product of specific social, cultural, and personal experience. The acceptance or refusal of a scientific theory and the pursuit or abandonment of a certain research direction have not always been based on true scientific merits. Scientists are humans too: they can be very personal, emotional, and political; they also make mistakes, even big ones; they also compete, increasingly fiercely, for job, money, fame, or anything else. Each of these factors could play very important roles in the development of one's scientific position or academic career.

The development of a scientific field has rarely been a process of systematically and constantly examining scientific ideas based on facts and scientific merits. Instead, it is very dependent on history and tradition. Inadvently, this process has led some errorneous theories to be accepted, even for a long time, while some right ones were refuted for reasons other than scientific. There are plenty of unfortunate examples like this in the history of science.

I am interested in studying the history and mechanism for a scientific theory's emergence, evolution, acceptance, or refusal in all relevant social, cultural, and personal background, during which its scientific merits will be better judged. My focus is in biology, some of the questions I am particularly interested in include:

1. What social and academic environments created the rise and/or fall of different evolutionary theories?
2. How has people's understanding of genetics evolved? How has the concept of gene evolved?
3. What was expected, what has been achieved, and what else needs to be done in genomics?
4. How has pop culture affected scientific understanding and communication as a whole?
5.How have the traditional publication mechanism, its characteristic journalistic quest for sensation, and its increasing commercialization for benefit affected scientific publication and progress? How can the publication process be improved to facilitate real, faster, and greater progress in science?

 

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Collaborations?

 

I seem to have more research ideas than that I can find enough time to work on. Though some of my ideas might seem ahead of their time, but I have found they would eventually be recognized or accepted by the scientific community. For example, quite some years ago when I was a graduate student, I was pondering if other biochemical factors than DNA could also affect inheritance. This would include epigenetic modifications on DNA but might also include other small molecules (like small RNAs as we know today). However, this sounded heretic to many others at that time. But a few years later, there was a burst of interests in epigenetics, starting in molecular biology. Now, it is one of the hottest fields in biology, and epigenetic regulation has been found to play critical roles in major biological processes (like cell differentication and tissue/organ formation) and the occurrence of environmentally-caused diseases (like cancer).

 

So I welcome collaborations in research and writing, particularly in evolutionary biology, genomics, bioinformatics, and science education. The interdisciplinary approach I take in research and the diverse set of expertises I have developed should hopefully make our collaborations easier, more meaningful, and more fruitful.


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