Mark Welch, D. Lab

David Mark Welch
Director of the BPC
Associate Scientist

p: 508 289 7377
f: 508 457 4727

Dr. David Mark Welch is an evolutionary biologist with a background in biochemistry and molecular biology.  His research spans processes of metazoan genome evolution to how rare and unknown microbes shape ecosystems, and is united by an overarching interest is the molecular mechanisms by which natural selection and evolutionary history create biological diversity.  As a graduate student with Matthew Meselson, Mark Welch found the first molecular evidence for the long-term absence of meiosis in an animal, which ushered in a new interest in using molecular genetic tools to study asexual evolution.  His continued research in this area led to a mature theory uniting unique aspects of the ecology, genome evolution, and DNA repair processes of these animals, bdelloid rotifers, to explain their unexpected evolutionary success.  Elements of this synthesis have been confirmed and expanded with the recent sequencing of a complete bdelloid genome, an effort of Mark Welch, JBPC scientist Irina Arkhipova, and an international team of collaborators.  The focus of his lab’s current research in this area is the novel antioxidant and DNA repair pathways of bdelloids.  The Mark Welch lab is also leveraging previous work exploring the ecological and evolutionary dynamics of sex and speciation in rotifers to investigate cellular, molecular, and genetic processes of aging from the perspective of evolutionary ecology and comparative genomics. Through collaborations with other scientists at the JBPC, Mark Welch extends his exploration of biological diversity to the realm of microbes. He led the development of the bioinformatics tools necessary to analyze the first massively-parallel tag sequence datasets that demonstrated the existence of a “rare biosphere” of microbial taxa.  The rare biosphere is predominantly made up of microbes that are very different from known species and may serve as a vast reservoir of genomic innovation, which could explain how microbial communities recover from environmental catastrophe and why every new microbial genome sequenced offers so much genetic novelty.

The Consequences of Long-Term Asexuality

The bdelloid rotifer Macrotrachela quadricornifera

While there is a rich body of theory supporting various explanations for the prevalence of sex, what has been lacking is an experimental model of long-term asexual evolution– an exception to the general rule that the loss of sex leads rapidly to extinction. The class Bdelloidea, a group of more than 370 species of micro-invertebrates in the basal metazoan phylum Rotifera, may be such a system.
Bdelloid rotifers are common aquatic invertebrates a few tenths of a millimeter long. Characterized by their ciliated head structure and bilateral ovaries, they have ganglia; muscles; digestive and secretory organs; photosensitive and tactile sensory organs; and structures for crawling, feeding, and swimming. Bdelloid eggs are produced from oocytes by two mitotic divisions, without chromosome pairing and without reduction in chromosome number, each oocyte yielding one egg and two polar bodies. Measured values of the DNA content of bdelloid oocyte nuclei range from approximately 500 to 2,000 Mbp, depending on species.

Despite much observation of field and laboratory populations since bdelloid rotifers were described by Leeuwenhoek more than 300 years ago, neither meiosis, males, hermaphrodites, nor vestigial male structures have ever been demonstrated. Cytological and molecular genetic studies have provided evidence that bdelloids evolved from a common ancestor that lost sexual recombination (meiosis and syngamy) about 100 million years ago.
Our laboratory, in collaboration with the laboratory of Adjunct Scientist Matthew Meselson at at Harvard University, is investigating the evolution of bdelloid genomes using a combination of cytology, genomic sequencing, phylogenetics, and bioinformatics. This project is funded by the Division of Molecular and Cellular Biosciences of the NSF.
In collaboration with the laboratory of John Logsdon at the University of Iowa, we are investigating the fate in bdelloid genomes of genes that encode proteins primarily or exclusively used in meiosis in other metazoans. Canonical preservation of these “meiosis specific” genes in bdeloids would suggest that bdelloids still engage in meiosis or in some sort of meiosis-like process. The loss of some genes and the novel evolution of others may indicate that the retained genes have been co-opted for other functions, such as the repair of DNA damage associated with desiccation. This project is funded by the Division of Genetics and Develpmental Biology of the NIGMS.

The picture above shows the bdelloid rotifer Macrotrachela quadricornifera.  The large oval is an embryo which will undergo direct development into a juvenile.  The inset shows the oocytes (collection of small cicles) in an ovary surrounded by the nuclei of the vitallarium (larger cicles) which provides nutrients to the developing embryo.  An oocyte will develop without chromosome reduction or pairing into an embryo, which will be a  clone of the mother.  A female produces 15-30 eggs during a 25-40 day lifespan under laboratory conditions. 

The Ecological and Evolutionary Dynamics of Sex

The bdelloid rotifer Macrotrachela quadricornifera

The paradox of sex is particularly striking in cyclically parthenogenetic species, where the majority of reproduction is asexual but environmental cues trigger episodic sexual reproduction. Populations of cyclically parthenogenetic species readily lose the ability to undergo meiosis, becoming obligately asexual, yet both sexual and asexual reproduction are maintained at the species level. This suggests a dynamic interaction between reproductive mode, fitness, and population ecology. Of central importance to understanding this dynamic is the evolution and ecological role of the genes that determine the frequency and prevalence of sex in cyclically parthenogenetic populations. Ultimately, these genes influence genomic diversity, rates of adaptation and speciation, and levels of biocomplexity in ecosystems.
In collaboration with Terry Snell and Julia Kubanek at Georgia Tech, we are isolating and characterizing the genes responsible for inducing mixis and for mate recognition in monogonont rotifers&emdash;one of the largest, most successful groups of cyclical parthenogens. The Snell laboratory has purified the Mixis Induction Protein and the Mate Recognition Protein from the monogonont B. plicatilis, and we have used the N-terminal sequence of MRP to isolate a candidate MRP gene. We are currently isolating a gene corresponding to the N-terminus of MIP, while the Snell lab is working to eliminate mate recognition through RNAi using the candidate MRP gene. This project, which is funded is funded the NSF Biocomplexity in the Environment Program, employs a combination of biochemical, genetic, genomic, bioinformatic, and modeling approaches to investigate natural and laboratory populations that have lost or maintained sex under a variety of ecological conditions. By tracking the evolution of these genes and their interaction with the genome and the environment we hope to understand how genotype and environment interact to regulate sex and determine its frequency in cyclical parthenogens.

The monogonont rotifer Brachionus plicatilis (see picture above, carrying a developing egg) is facultatively sexual.  Reproduction is generally asexual (amictic).  When a population reaches a certain density, a percentage of females will produce daughters that will then produce eggs by meiosis.  The Snell lab has determined that the mixis inducing factor is a secreted peptide.  If unfertilized, a haploid egg produced by a mictic female will develop into a highly reduced, haploid male that will attempt to mate with a mictic female.  Males recognize a 28 kD peptide on the corona of the female called the Mate Recognition Protein; the Snell lab has isolated and characterized this protein and we have isolated the gene which encodes it.  Fertilized haploid eggs become diploid resting eggs capable of desiccation tolerance and over-wintering.   Resting eggs develop into amictic females.  The sexual cycle is not required for short-term evolutionary success and it is often lost in laboratory cultures.

Monogonont Rotifers as a Model to Investigate the Biology of Aging
The traditional non-vertebrate metazoan model systems C. elegans and D. melanogaster are more closely related to each other than originally thought (both belong to the Ecdysozoa superphylum), and both have undergone extensive gene loss since they and humans shared a common ancestor. It is likely that new genes with relevance to human aging are yet to be identified in non-Ecdysozoan animal groups. Rotifera is a large, diverse phylum evolutionarily distinct from Ecdysozoa; in fact, rotifers occupy the basal position among triploblast animals that nematodes were assumed to before the discovery of their closer affiliation to arthropods in the 1990s. In addition to the short generation time and ease of culturing common to many model systems, monogonont rotifers have specific features that make them an attractive model system for aging studies, including: 1) a history of aging related research extending back nearly a century; 2) asexual propagation of clonal cultures, so that experiments can take place in the same genetic background, without the potential inbreeding depression imposed on isogenic lines; 3) sexual and asexual reproduction in the same genetic background; 4) haploid males, allowing direct expression of alleles and simplifying crosses in the absence of complex marker chromosomes; 5) production of highly stable diapausing eggs; 5) many closely related strains and species that differ in life history traits; and 6) A well developed tool box of genetic resources including partially sequenced genomes and transcriptomes, and a working RNAi protocol.
In collaboration with Terry Snell at Georgia Tech, we are determining the effects on aging rate and longevity of dietary restriction, oxidative stress, and elevated temperature in multiple closely related strains of the Brachionus plicatilis species complex under both sexual and asexual growth conditions, including quantification of oxidative damage of proteins, lipids, and DNA. We will identify genes involved in aging and longevity by examining the transcription profiles of rotifers of different ages under these conditions and confirm the activity of specific genes by RNAi, qtPCR, and quantification of oxidative damage. To understand the role of diapause in aging we will examine the mechanisms by which diapause in Brachionus alters tissue homeostasis, suspends metabolism during dormancy, and stimulates tissue repair following dormancy; and by examining the effect of aging on rotifers that have been kept in a dormant state for up to 25 years. Our goal is to determine which theories of aging best account for differences in aging rate and longevity in rotifers and to identify new genes involved in regulating these processes; and to understand the relationships between aging and reproductive mode (sexual vs asexual) and between aging, homeostasis, and tissue repair associated with diapause. This project is funded by the National Institute on Aging.

Exploring Microbial Diversity and the Rare Biosphere
In traditional studies of microbial diversity based on Sanger sequencing of clone libraries, a few dominant populations have masked the presence thousands of low-abundance phylotypes, many of which are very different from anything in reference databases. This vast realm of highly diverse, low-abundance phylotypes constitutes the rare biosphere. The sum of all different kinds of organisms in the rare biosphere represents a significant fraction of complete microbial communities and has temporal and spatial dimensions that impact our perceptions of microbial ecology. Competing hypotheses about the distribution of the rare biosphere include 1) A large number of highly-diverse, low-abundance phylotypes are globally distributed 2) The rare biosphere represents the dispersion of microbes from a large number of yet to be discovered sites with abundant, endemic populations and 3) Low-abundance taxa are vestiges of the legacy of microbes that previously dominated a microbial community. We are testing these hypotheses using our database of more than 30 million V6 tag sequences from dozens of projects representing more than 700 samples, including all 13 of the aquatic Long Term Ecological Research Sites funded by the NSF; Ocean Drilling Project sites in the Atlantic and Pacific; time series sampling from the Hawaiian Ocean Time Series and the North Sea; and additional sites in marine surface and deep water, kelp, coral, sediment, basalt, coastal estuaries, marshes, and sand. Key questions include: Does membership in the rare biosphere across spatial-temporal boundaries correlate with chemical and physical gradients or with differences in the dominant members of the microbial community? Are some members of the rare biosphere always part of the long tail in diverse ecosystems? Which microbial taxa define a planet-wide rare biosphere? This project is funded by the Alfred P. Sloan Foundation.


Kristin Gribble
Assistant Research Scientist
p: 508 289 7194
f: 508 457 4727


Bette Hecox-Lea
Research Assistant II

p: 508 289 7196
f: 508 457 4727


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