Keller Lukas

Untersuchung einer Gemspopulation ohne Kontakt zu Nutztieren
Anthelminthic resistance across intestinal parasites of different host species

Project Number: CH-2507
Project Type: Master
Project Duration: 04/01/2005 - 03/31/2007 project completed
Funding Source: other ,
Project Leader: Prof. Lukas Keller
Institut für Evolutionsbiologie und Umweltwissenschaften
Universität Zürich
Winterthurerstr. 190
8057 Zürich
Phone: ; +41 (0) 44 635 47 50
FAX: +41 (0) 44 635 68 18
e-Mail: lukas.keller(at)

related to this project.
for which the project has a relevance.

Research Areas:

fundamental biology

genetic drift

Today measuring the main population genetics variables is no longer as challenging as it was before all the modern molecular tools were invented. But just knowing the parameters doesn't enlighten the whole history of evolution. Parameter values can only be properly interpreted if the forces are understood that have led to their present state. Thus, a better understanding is needed of the processes that can alter the gene pool.
Mutation and genetic drift are stochastic processes that affect allele frequencies independently in each population1,2. Gene flow is the counterpoise that equalises allele frequencies among populations. Assuming that there is no selection, this leads to an equilibrium. Hence, by looking at where this equilibrium lies, you can conclude how strong gene flow is compared to drift. Therefore, to measure gene flow, people often focus on silent mutations in the DNA or on mutations in a non coding region, for instance in microsatellites. From that they deduce how distinct the populations are. Assuming equilibrium conditions, you can come up with a measure of gene flow. This approach has a big disadvantage. Genetic drift is linked to the population size, which is not necessarily constant over time. Thus, gene flow is variable, too, and an equilibrium will not be attained.
Alternative approaches consider selection acting as an additional force on a population's gene pool. Selection leads to local adaptation of the population. Selection is directional and can affect a population much more strongly than genetic drift. Gene flow introduces different alleles from population underlying other selective pressures. In most cases these introduced alleles are selected away before long in the new location. Thus, for selected alleles, the similarities in allele frequencies brought about by gene flow require ongoing gene flow.
The big challenge in estimating the gene flow versus selection is to understand what alleles are favoured in what intensity by what selective regime. Seldom all factors are known. Fortunately there is an actual case for my study.

Leading questions:
o Is there an exchange of nematodes and thus gene flow between domestic and wild animals? A strong indication would be the discovery of resistant nematodes in wild animals. Because there is no selection for BZ resistance in wild animals, any resistant worm must have entered the population through gene flow.
o How extensive is gene flow between domestic and wild animals? What is the observed frequency of susceptible and resistant alleles?
o Can I detect a reduced frequency of resistant worms in domestic animals that experience high rates of exchange with nematodes of wild ungulates? Is gene flow high enough to thwart local adaptation of domestic worm populations under selection of the drug?
o Does gene flow vary for different resistance alleles (different codons)? The proportion of every allele can reveal something about the gene flow pattern. In the present study and time permitting, I focus on the mutations at residues 167 and 200 on both isotypes I and II.
o Does gene flow vary in different nematode species? If possible I will investigate Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus colubriformis. In these species, several studies have investigated BZ resistance and sequences of the relevant parts of the genome are available17. All species vary in some parameter of population dynamics; therefore different levels of gene flow can be expected. Larvae of Haemonchus contortus are supposed not to survive strong winters in higher altitude areas. And Trichostrongylus colubriformis may disperse less than the others due to laying fewer eggs.
o What levels of gene flow can be observed among wild animals? If there are resistance alleles in some populations of wild animals that meet with domestic ones, do they also spread into isolated populations? I therefore would like to measure allele frequencies in an isolated population, although I don't know yet if such a population exists in the crowded Swiss Alps. Further contact to game wardens is necessary to determine the feasibility of this part of the project.
o What spatial patterns of the spread of resistance genes would we expect theoretically? I will write a computer programme to test the influence of several parameters and to get a rough idea of what can be expected theoretically. The programme should assist me in determining the quantitative dimension of the problem.
o What would be the predictions for different encounter rates of wild and domestic animals?
o What effects have differing movement rates of domestic animals within Switzerland and across the borders to other countries?
o What are the effects of different selection regimes due to variable application of anthelmintica?
o There is debate whether the BZ mutations conferring resistance are costly to the organism in the absence of the drug or not8,18,19. Such costs would cause selection against resistant alleles in wild animal populations. The programme will allow me to determine the effects of various levels of costs on resistance evolution.

The investigation should be carrying out in areas where wild and domestic animals meet often enough to expect an exchange of gastrointestinal nematodes. The wild animal populations should live next to other populations of wild animals which meet domestic animals much less frequently. I could then compare the two populations and measure gene flow among wild animal populations. I haven't identified such a site yet but I am working with game wardens to identify suitable areas.
The decision what kind of host I will investigate depends on the study site. For domestic animals, one has to take into account that sheep are four times more common in the Alps than goats. But goats are more closely related to Alpine ibex and Alpine chamois and would therefore be a more desirable study species. Alpine ibex would be the preferred wild species because it is even closer related to goats than chamois4. But the habitats of Alpine ibex are probably more removed from the pastures of domestic animals. Furthermore the congruence in the spectrum of common gastrointestinal nematodes is greater between Alpine chamois and domestic animals than between Alpine ibex and domestics.

Last update: 12/16/16
Source of data: ProClim- Research InfoSystem (1993-2020)
Update the data of project: CH-2507

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