Coalescent Time Estimation

We developed an estimator of first coalescent time, which is the time when a copy of a gene most recently shared ancestry with other copies of that gene. This is also an estimate of the upper bound of when a mutation has arisen, and it can be used to study the ages of alleles that are found in a population. The method can be applied to the very rarest alleles found only once in a sample, even in studies of many thousands of genomes. We tested the method extensively, found it performs well, and can be used under a wide variety of conditions. We applied it to 1000 Genomes project data (26 populations) and the UK10K data (over 7000 genomes) and found clear evidence that alleles that change proteins are younger than alleles that do not, as expected. We also observed wide variation in the ages of alleles at low frequency among the 1000 Genome project populations, indicating that our method could be used to study the demographic history of human populations. Going forward, the estimator should be useful for many kinds of questions in population genomics, particularly as sample sizes continue to grow.

Divergence Population Genetics

How have populations diverged to become new species?  One way to answer is to sample the genes from the populations and species in question,  and then figure out how divergence happened using the patterns of variation you find in the genes.  We call this process  "Divergence Population Genetics"  (or sometimes just "DPG") because it uses method of population genetics and applies them to questions on divergence.

Chichlid Fishes of the African Great Lakes

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 few 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 and again in May of 2008 the Hey lab traveled to Malawi to study the divergence among the Mbuna (members of the rock-dwelling species of Lake Malawi).

Evolution of Humans and Apes

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As shown in this famous figure from Huxley's  1863 book "Evidence on Man's Place in Nature",  humans have a great deal of similarity with the other great apes.  Today we know that this similarity extends also to the DNA level were humans and chimpanzees are about 99% identical. 

Based on fossil evidence modern humans appear to have evolved in Africa over 150,000 years ago.  In the time since then our ancestors came to populate,  not only Africa but much of the remainder of the globe.  It is possible, using data from present-day peoples and population genetic methods, to figure out many of the details of this history.

The evolutionary lineage leading to modern humans appears to have separated from the lineage leading to our sister species,  chimpanzees and bonobos,   about 6 or 7 mililion years ago.   We can study this divergence process, as well as the divergence of chimpanzees and bonobos from each other,  using many of the same population genetic tools that we use to study the spread of human populations.

Understanding Species and Populations

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In the 20th century the modern concept of a biological population was developed.  Biological populations are interbreeding communities of organisms that share in the evolutionary process.  However populations are not always easy to study or identify.

At or above the level of populations,  biologists also work with species. The idea of a species, or a kind of organism, has been around for a very long time - perhaps into the very roots of human language. 

Paradoxically  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.

Other Projects

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Evolution in the genus Drosophilia

For many years research in the Hey lab was primarily focused on the evolution of flies in the genus Drosophilia.

Caenorhabditis elegans population genetics

The soil nematode C. elegans has rapidly become the model organism of choice for many genetic, developmental, and functional studies. However until recently little was 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.

With grad student Arjun Sivasundar we undertook the study of poplymorphism and outcrossing levels in natural populations.

Genome Content, Codon Bias, Recombination and Natural Selection

Because of the redundancy of the genetic code the genomes of most species use multiple codons for the 18 amino acids that have multiple codons.  Unequal usage of codons (called "codon bias") can be used as an indicator of natural selection acting on codon usage,  generally to optimize the process of protein translation.  With Richard Kliman we investigated both the natural selection and mutational contributions to codon bias variation among the genes of Drosophila melanogaster.  We found 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.

Over time this work lead to new investigations on the origins of recombination and the interaction between recombination and natural selection.