Department of Biology

Program

Evolution, Ecology & Behavior

Research Areas

• Chromatin, Chromosomes, and Genome Integrity
• Evolution
• Genomics and Bioinformatics

Education

Ph.D., University of Minnesota, 1977

Awards

Member, US National Academy of Sciences, 2009

Fellow, American Academy of Arts and Sciences, 2002

 

Research Description

Our research is focused on mechanisms of evolution at the gene, genomic, cellular, and phenotypic levels, with special attention being given to the roles of mutation, random genetic drift, and recombination. For these purposes, we are currently utilizing several model systems, the microcrustacean Daphnia, the nematode Caenorhabditis, the ciliate Paramecium, and the unicellular alga Chlamydomonas.  In addition, comparative analyses of completely sequenced genomes are being performed to shed light on issues concerning the origins of genomic and gene-structural complexity. Most of our empirical work is integrated with the development and use of mathematical theory in an effort to develop a formal understanding of the constraints on the evolutionary process. Evolution is a population-level process, and the underlying philosophy of our research is that "nothing in evolution makes sense except in the light of population genetics."

The Evolution of Genome Complexity.

Despite the common view that a causal link exists between complexity at the genomic and organismal levels, little thought has gone into the mechanisms that are responsible for the origin of the fundamental features of the eukaryotic genome. Using population-genetic principles as a guide to understanding the evolution of duplicate genes, introns, mobile-genetic elements, and regulatory-region complexity, our work is advancing the hypothesis that much of eukaryotic genomic complexity initially evolved as a passive indirect response to reduced population size (relative to the situation in prokaryotes).

One of the primary goals of our work on gene duplication is to explain the shortcomings of the classical model, which postulates that the usual fates of duplicated genes are either conversion to a nonfunctional pseudogene or acquisition of a new function. We believe that duplicate genes are frequently preserved through a partitioning of functions of ancestral genes, rather than by the evolution of new functions. We have developed methods to estimate the rate of origin and loss of duplicate genes, and are currently extending this work to understand the evolutionary dynamics of duplication spans internal to genes. Our empirical work on the evolutionary fates of duplicate genes is focused on the genomes in the Paramecium aurelia complex, which are products of an ancient polyploidization event that appear to have generated a species radiation.

In addition, we have recently shown that the modular regulatory-region architecture common in eukaryotes can spontaneously emerge in populations of sufficiently small size. These results, along with our theoretical work on network evolution, challenge the popular idea that modularity arises as a direct consequence of selection for morphological complexity, and by extension raise questions about the common assumption that natural selection was responsible for the emergence of multicellularity.

Our work on intron evolution is focused on the hypothesis that newly arisen introns are typically mildly deleterious, and a major goal is to understand how introns eventually came to be integrated into fundamental aspects of gene-transcript processing.  We are currently attempting to learn how the complex intron-splicing machinery, the spliceosome, evolved and diversified among various phylogenetic lineages. We have hypothesized that intron proliferation was facilitated by the evolution of nonsense-mediated decay (NMD), an mRNA surveillance mechanism that uses exon-junction information as an orientation mechanism for identifying aberrant premature stop codons. Empirical work in this area is being pursued with Daphnia populations, which have revealed an unprecedented level of intron gain (to the extent that presence/absence polymorphisms, as well as parallel intron gains, can be found within populations). We hope that the latter work in particular will eventually yield an answer to the long-term mystery as to the origins of introns.

Finally, as an initial foray into microbial evolution, we are studying the evolution of a unique series of endosymbiotic bacterial species inhabiting Paramecium. Known as “killer” bacteria because of their effects on non-killer bearing Paramecium, these microbes are providing us with a unique perspective on the consequences of a reduction in global effective population size on the evolution of genomic architecture. Complete-genome sequencing of several strains has revealed an enormous proliferation of mobile-genetic elements.

The Role of Mutation in Evolution.

Although mutations provide the ultimate material upon which natural selection depends, most mutations are deleterious, and in certain population settings, can lead to a substantial fitness load. We are attempting to quantify rates and phenotypic effects of mutations, with an ultimate goal of evaluating their contribution to both adaptive progress and extinction risk. This work exploits a mutation-accumulation strategy in which lines are propagated as single individuals to minimize the ability of natural selection to influence the fate of newly arisen mutations. Our long-term lines of Daphnia, C. elegans, and Paramecium, in some cases exceeding thousands of generations of divergence, are providing an unprecedented opportunity for studying the mutation process. Molecular analyses of these lines by complete-genome sequencing are yielding the first direct quantitative estimates of the rate and spectrum of mutations at the DNA level, revealing substantially higher estimates than had previously been obtained by indirect phylogenetic comparisons. Our work on mutation extends to the development of population-genetic theory for the evolution of the mutation rate itself, and to obtaining a general understanding of the consequences of somatic mutations for the evolution of multicellularity.

The Role of Recombination in Evolution.

Sexual recombination provides a powerful means for producing multi-locus genotypes with high fitness, but also has the negative side-effect of breaking apart the very same coadaptive complexes of genes. A great deal of theory has been developed to help explain the phylogenetic distribution of recombination, but the key biological observations for testing the various hypotheses remain to be developed. To this end, we are exploiting the microcrustacean Daphnia pulex, which consists of both sexual and asexual races of various evolutionary ages. An additional remarkable feature of this system is its "living-fossil" record -- from the sediment cores of lakes, resting eggs from the past 200 years can be hatched and maintained clonally, and DNA can be extracted from remnants of up to 2000 years old.

With numerous collaborators, we have initiated a Daphnia Genomics Consortium (http://daphnia.cgb.indiana.edu/ ), the goals of which are to catalogue, map, and characterize the functions of the majority of genes in D. pulex. These tools will then be exploited to understand the molecular mechanisms of phenotypic evolution in the context of natural ecological settings, a luxury that is not available to most model invertebrate systems. Recent tool development includes: sequencing of the complete genome; a high-density genetic map based on ~200 microsatellite loci; complete sequencing of a full-length cDNA library of ~200,000 transcripts; and production of microarrays for functional analysis.

With colleagues, we are now using the D. pulex system to improve our understanding of the evolutionary causes and consequences of recombination. Specific projects include: the isolation and characterization of the genes responsible for meiosis suppression in obligate asexuals; quantification of the rate of accumulation of deleterious mutations in asexual vs. sexual lineages; estimation of the rate and tempo of allele and genotype turnover in natural populations; and quantification of the influence of recombination on the activity of mobile genetic elements. To this end, we are sequencing several complete genomes of obligately asexual lineages of Daphnia and their closely related sexual relatives in an effort to find the molecular signature of recombination suppression.

Methodology for the Analysis of High-Throughput Genomic Data.

The rapid emergence of technological innovations in genome sequencing has resulted in a situation where it will soon be possible to sequence multiple genomes from natural populations. In anticipation of such data, and the enormous challenges that come with them (most notably, incomplete sampling of parental alleles and errors in sequence reads), we have begun to develop a new generation of maximum-likelihood methods for estimating a broad array of population-genetic parameters, including nucleotide heterozygosity, linkage disequilibrium, and the allele-frequency spectrum.

Select Publications

Ossowski, S., K. Schneeberger, J. Lucas-Lledó, N. Warthmann, R. M. Clark, R. G. Shaw, D. Weigel, and M. Lynch. 2009. The rate and molecular spectrum of spontaneous mutations in Arabidopsis thaliana. Science 327: 92-94.

Li, W. A. E. Tucker, W. Sung, W. K. Thomas, M. Lynch. 2009. Extensive, recent intron gains in Daphnia populations. Science 326: 1260-1262.

Gao, X., and M. Lynch. 2009. Ubiquitous internal gene duplication and intron creation in eukaryotes. Proc. Natl. Acad. Sci. USA 106: 20818-20823.

Rho, M., M. Zhou, X. Gao, S. Kim, H. Tang, and M. Lynch. 2009. Parallel mammalian genome contractions following the KT boundary. Genome Biology and Evolution 2009: 2-12.

Catania, F., F. Wurmser, A. A. Potekhin, E. Przyboś, and M. Lynch. 2009. Genetic diversity in the Paramecium aurelia complex. Mol. Biol. Evol. 26: 421-431.

Denver, D. D., P. C. Dolan, L. J. Wilhelm, W. Sung, J. I. Lucas-Lledó, D. K. Howe, S. C. Lewis, K. Okamoto, M. Lynch, W. K. Thomas, and C. F. Baer. 2009. A genome-wide view of  Caenorhabditis elegans base-substitution mutation processes. Proc. Natl. Acad. Sci. USA 106: 16310-16314.

Lynch, M. 2008. Estimation of nucleotide diversity, disequilibrium coefficients, and mutation rates from high-coverage genome-sequencing projects. Mol. Biol. Evol. 25: 2421-2431.

Lynch, M. 2008. The cellular, developmental, and population-genetic determinants of mutation-rate evolution. Genetics 180: 933-943.

Lynch, M., A. Seyfert, B. Eads, and E. Williams. 2008. Localization of the genetic determinants of meiosis suppression in Daphnia pulex. Genetics 180: 317-327.

Lynch, M. 2007. The frailty of adaptive hypotheses for the origins of organismal complexity. Proc. Natl. Acad. Sci. USA 104 (Suppl.): 8597-8604.

Lynch, M. 2007. The Origins of Genome Architecture. Sinauer Assocs., Inc., Sunderland, MA.

Lynch, M., B. Koskella, and S. Schaack. 2006. Mutation pressure and the evolution of organelle genome architecture. Science 311: 1727-1730.

Paland, S., and M. Lynch. 2006. Transitions to asexuality result in excess amino-acid substitutions. Science 311: 990-902.

Lynch, M. 2006. The origins of eukaryotic gene structure. Mol. Biol. Evol. 23: 450-468.

Lynch, M., and J. B. Walsh. 1998. Genetics and Analysis of Quantitative Traits. 980 pp. Sinauer Assocs., Inc., Sunderland, MA.