Jody Hey                  Evolutionary Genetics

  Professor    -     Department of Genetics     -   Rutgers University

Hey Lab Research Publications Software, Data Contacts, People

 

Listing of papers on PubMed

To find out more about a research area click on a picture or adjacent text

Genetics of Speciation in the Cichlid fishes of Lake Malawi

The Species Problem

Population Genetics of Caenorhabditis elegans

Genetics of Human Origins

Divergence Population Genetics

Drosophila Speciation Genetics

The Evolutionary Origins of Recombination

Genome Content, Codon Bias and Natural Selection

Much of this work would not have been possible without support from Rutgers University, the National Science Foundation, and the National Institutes of Health.  

 

Genetics of Speciation in the Cichlid Fishes of Lake Malawi

Lake Malawi, like the other Great African Lakes,  is home to hundreds of described species in the family Cichlidae. In the case of Lake Malawi, nearly all of these species arose within the two million years that the lake has been in existence. There are active debates on the actual mode of speciation, and the kinds of divergent natural selection that may have caused the species.  In December of 2002 the Hey lab traveled to Malawi to collect samples from three genera of Mbuna (members of the rock-dwelling species of Lake Malawi).  Our goal is to assess the role that gene exchange plays in the speciation process.  We are using a newly developed type of genetic marker which include Short Tandem Repeat regions (STRs, or microsatellites) and the flanking unique sequence region.  These 'HapSTRs'  (i.e. haplotypes with STRs) should permit high resolution of recent events including gene flow,  as needed for these recently formed species.

Won YJ, Wang Y, Sivasundar A, Raincrow J, Hey J. 2006. Nuclear gene variation and molecular dating of the cichlid species flock of Lake Malawi. Mol Biol Evol 23:828-837.

Won, Y. J., A. Sivasundar, Y. Wang, and J. Hey. 2005. On the origin of Lake Malawi cichlid species: a population genetic analysis of divergence. Proc Natl Acad Sci U S A 102:6581-6586.

Hey, J., Y.-J. Won, A. Sivasundar, R. Nielsen, and J. A. Markert. 2004. Using nuclear haplotypes with microsatellites to study gene flow between recently separated Cichlid species. Molecular Ecology 13: 909-919

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The Population Genetics of Caenorhabditis elegans

The soil nematode C. elegans has rapidly become the model organism of choice for many genetic, developmental, and functional studies.  However little is known about its evolutionary history or of its basic population biology.  What few studies that have been done reveal a surprisingly low amount of genetic variation at the DNA sequence level.   We are beginning investigations of the structure of natural populations of C. elegans.

Recently with grad student Arjun Sivasundar we developed a new method for sampling C. elegans from nature using a novel RNA interference (RNAi) approach.

Sivasundar, A., and J. Hey. 2005. Sampling from Natural Populations with RNAi Reveals High Outcrossing and Population Structure in Caenorhabditis elegans. Current Biology 15:1598-1602.

Sivasundar, A., and J. Hey. 2003. Population Genetics of Caenorhabditis elegans. The paradox of low polymorphism in a widespread species. Genetics 163:147-57.

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Divergence Population Genetics 

          Divergence Population Genetics (DPG) is a name given to the study of population, or species, divergence using population genetics.  Traditionally population genetic theory was fairly limited with regard to discerning the parameters associated with the divergence of populations.  In recent years newer likelihood methods, based on coalescent theory, have lead to new methods for studying the roles of genetic drift, mutation, and natural selection in the divergence of populations. 

         The coalescent is a stochastic process (or a family of stochastic processes) that are very useful for modeling the depths of gene trees (branching evolutionary trees that describe the ancestry of a set of homologous DNA sequences). Coalescent models are analytically tractable, easily simulated, and are explicitly focused on the properties of samples of DNA sequences (and not on entire populations of items). Thus they are very suitable for developing probabilistic models of evolutionary processes and their effects on the gene trees of DNA sequences. Most of my theoretical research has been directed at coalescent models within the context of species divergence, particularly on the use of fixed and shared differences between species to estimate parameters in speciation models.

        Recent theoretical and statistical work has focused on the "Isolation with Migration" model of population divergence.  This is a general model, with many parameters, that can encapsulate many of the processes that evolutionary biologists think about when wondering how divergence has occurred.  Much of this work has been done in collaboration with Rasmus Nielsen (University of Copenhagen).

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Drosophila Speciation Genetics

Research on the genetics of speciation, and of species divergence, is difficult. Genetics can be done on organisms from closely related populations that may be incipient species, however it is not known whether present day incipient species are representative of speciation events that occurred long ago and that have lead to what are now clearly unambiguous species. On the other hand, genetics cannot usually be done on clearly distinct species that have separated long ago, for the simple reason that they cannot usually be crossed to yield fertile progeny. In recent years we have bridged a gap of sorts and undertaken the approach of comparing the DNA sequences from individuals randomly sampled from closely related, yet clearly distinct, species. A typical data set includes multiple sequences for a nuclear gene randomly drawn from each of two or more closely related species. Furthermore, we typically extend these data sets to include multiple genetic loci. One of the major discoveries to come from this research is that the age of variation within species is often as great or greater than the time since the formation of sister taxa. In short, closely related species often reveal DNA sequence variation that is shared since the time of common ancestry. The presence of this variation means that it is possible to ask questions about forces (traditionally associated with population genetics) over a time frame that is more often associated with macroevolutionary issues (i.e. the divergence of species). In effect, we are doing population genetics on relatively ancient speciation events (105 - 106 years, which is ancient from the viewpoint of traditional population genetics). Much of the research also focuses on the variation that is observed among loci in the history they reveal. This variation among loci can reveal historical patterns of gene flow and natural selection associated with species formation.

In practice this research entails a large amount of PCR and DNA sequencing. The analysis of the data also often entails a fair amount of theoretical work, both analytical and via computer simulation. In general the empirical research focus is very closely linked with the use of coalescent models and my theoretical research.

To date this research has been carried out on several species groups of Drosophila. Including the D. melanogaster complex; the virilis phylad of the D. virilis group; and in D. pseudoobscura and close relatives.

The Drosophila melanogaster  species complex.

Drosophila pseudoobscura  and closely related species.

Drosophila virilis and closely related species.

Other Related Papers

  • Wakeley, J. an J. Hey. 1998. Testing speciation models with DNA sequence data. pp157-175 in Molecular Approaches to Ecology and Evolution. edited by R. DeSalle and B. Schierwater. Birkhäuser-Verlag, Basel.

  • Wakeley, J., and J. Hey, 1997. Estimating ancestral population parameters. Genetics 145: 847-855 .

  • Hey, J., 1994 Bridging phylogenetics and population genetics with gene tree models. in B. Schierwater, B. Streit, G. Wagner and R. DeSalle, eds. Molecular Approaches to Ecology and Evolution. Birkhäuser-Verlag, Basel.

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The Genetics of Human Origins

Patterns of DNA sequence variation within and among human populations shows a great deal of variation from one gene to another.  A fundamental question that arises in many evolutionary genetic contexts is: How much of this variation can be explained by historical demographic processes that act on all the genes in the genome, and how much remains to be explained by natural selection that acts on localized areas (individual genes and tightly linked genes) of the genome.  

Recently we have devised new approaches that permit us to develop more detailed pictures of how populations spread and diverged.  These methods make use of the 'Isolation with Migration' model, and have been developed in collaboration with Dr. Rasmus Nielsen (University of Copenhagen and Cornell University).

Several years ago I noticed that DNA sequence variation in nuclear genes did not show the same patterns as found in the DNA of the human mitochondria.   More recently, with Eugene Harris, we observed strongly contrasting patterns of variation at two X-linked genes, PDHA1  and Factor IX.  The human PDHA1 gene appears to have had an ancestral DNA that existed about 1.9 Million years ago.   We also observed a fixed DNA sequence difference at PDHA1 between samples collected within and outside of Africa.  When we studied the same samples at a different locus,  the gene for clotting factor IX,  we found a much shorter history with common ancestry less than 300,000 years.   The presence of such widely varying histories, for two randomly sampled X chromosome genes, suggests that human history has been one that elevates variation among loci, such that no-one locus can be expected to be a good indicator of human history.

 

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The Species Problem

One of the most pernicious uncertainties in evolutionary biology is the meaning of the word "species". This question, and the general absence of consensus on the best methods to identify species, have been called the species problem. The debate has raged at various levels and on various fronts for several decades, and it ranges over very practical applied aspects as well as over very theoretical and philosophical aspects. The debate is also played out on two very different fronts: the systematic front, where researchers are most concerned with methods of identification and classification; and the population biology front, where researchers are most concerned with a species as a kind (what kind?) of natural group- a level of biological organization.

The species problem is not just an academic debate, for it has a large effect on the way that biologists work to discover and preserve biological diversity.  In recent years, discussions over how to identify species and define "species"  have come to the fore in the literature on biological conservation.  Nor will they dissipate without some widespread recognition of the basic causes of our uncertainty.   

Recently I wrote a piece commenting on the use of the "concept" in the history of the species problem before and after Ernst Mayr's famous 1942 book (Mayr E. 1942. Systematics and the origin of species. Columbia University Press, New York.).

Hey J. 2006. On the failure of modern species concepts. Trends Ecol Evol 21:447-450.

A few years ago,  with several colleagues, we wrote an essay on confronting species uncertainty

Hey, J., R. S. Waples, M. L. Arnold, R. K. Butlin, and R. G. Harrison. 2003. Understanding and confronting species uncertainty in biology and conservation. Trends in Ecology and Evolution 18:597-603.

 Abstract: Recent essays on the species problem have emphasized the commonality that many species concepts have with basic evolutionary theory. Although true, such consensus fails to address the nature of the ambiguity that is associated with species-related research. We argue that biologists who endure the species problem can benefit from a synthesis in which individual taxonomic species are used as hypotheses of evolutionary entities. We discuss two sources of species uncertainty: one that is a semantic confusion, and a second that is caused by the inherent uncertainty of evolutionary entities. The former can be dispelled with careful communication, whereas the latter is a conventional scientific uncertainty that can only be mitigated by research. This scientific uncertainty cannot be `solved' or stamped out, but neither need it be ignored or feared.

Debates over species tend to be repetitive and obdurate, and biologists rarely treat the species-problem questions as they do other scientific questions.  In particular, they do not ask of what new information is needed to address the problem.   While on sabbatical in 1998 and 1999 I began a book that addresses both the evolutionary and the human cognitive aspects of the species problem.   The book was published in June 2001 by Oxford University Press.  It is entitled: Genes, Categories and Species: the evolutionary and cognitive causes of the species problem.   It contains a forward by John Maynard Smith. 

A short essay on the species problem, that describes some of the main themes developed in Genes, Categories, and Species was published in Trends in Ecology and Evolution

Hey, J., 2001 The mind of the species problem. Tr. Ecol. Evol. 16: 326-329.

Biologists often wish that the species problem would go away or that it can be ignored.  One of the best examples occurred in the founding of the All Species Foundation, which had the mission of discovering all (literally) species on the planet within a generation.   In 2002 several evolutionary biologists and I wrote a letter to the All Species Foundation, expressing strong support for the general goals of conservation and discovery, as well as strong concern that conservation and discovery efforts will be hampered if biologists  overlook the basic sources of species uncertainty.  To read the letter, click here. 

Well before Genes, Categories and Species , I spent a fair bit of time puzzling over the reality of species and definitions of the word "species".  The manuscript that resulted from those efforts is entitled "A Reduction of "Species" and a Resolution of the Species Problem" and it is available here.

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Genome Content, Codon Bias and Natural Selection

In some single celled organisms, it has been known for some time that natural selection acts on codon usage. However multicellular eukaryotes are expected to have smaller effective population sizes, and it had often been assumed that synonymous variation in protein coding regions of eukaryote genomes was not under selection. With Richard Kliman we investigated both the natural selection and mutational contributions to codon bias variation among the genes of Drosophila melanogaster. Perhaps our most significant finding was that regions of the genome that experience reduced recombination also have much reduced codon bias. Since natural selection is expected to be less effective in regions with low crossing over rates, this observation is exactly as expected if natural selection has contributed to the high codon bias observed in some genes.

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The Evolutionary Origins of Recombination

Recombination is the process whereby a segment of DNA breaks with a contiguous segment, and rejoins with a different DNA. It is a nearly ubiquitous process, occurring in prokaryotes, as well as eukaryotes. However the evolutionary advantage of recombination, the reason why it has evolved, is not known - though there are a large list of possible candidates. An investigation of this molecular behavior was done from a selfish gene perspective. The result is a very general expectation that recombination is expected to evolve as a byproduct of the conflicts that occur when multiple sites are simultaneously under linkage and selection.

Hey, J. 2004. What's so hot about recombination hotspots. Public Library of Science 2:0730-0733.    Full Text

Hey, J. 1998. Selfish genes, pleiotropy and the origin of recombination. Genetics 149: 2089-2097.

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web page last updated July 23, 2007 .