NSF Org:	DEB Division Of Environmental Biology
Recipient:	UNIVERSITY OF CHICAGO
Initial Amendment Date:	February 4, 1994
Latest Amendment Date:	February 4, 1994
Award Number:	9317683
Award Instrument:	Standard Grant
Program Manager:	Mark Courtney DEB  Division Of Environmental Biology BIO  Directorate for Biological Sciences
Start Date:	February 1, 1994
End Date:	June 30, 1997 (Estimated)
Total Intended Award Amount:	$145,000.00
Total Awarded Amount to Date:	$145,000.00
Funds Obligated to Date:	FY 1994 = $145,000.00
History of Investigator:	Deborah Charlesworth (Principal Investigator) debchar@pondside.uchicago.edu Brian Charlesworth (Co-Principal Investigator)
Recipient Sponsored Research Office:	University of Chicago 5801 S ELLIS AVE CHICAGO IL  US  60637-5418 (773)702-8669
Sponsor Congressional District:	01
Primary Place of Performance:	University of Chicago 5801 S ELLIS AVE CHICAGO IL  US  60637-5418
Primary Place of Performance Congressional District:	01
Unique Entity Identifier (UEI):	ZUE9HKT2CLC9
Parent UEI:	ZUE9HKT2CLC9
NSF Program(s):	POPULATION DYNAMICS
Primary Program Source:	app-0194
Program Reference Code(s):	9169, ENVI
Program Element Code(s):	117400
Award Agency Code:	4900
Fund Agency Code:	4900
Assistance Listing Number(s):	47.074

ABSTRACT

9317683 Charlesworth Mutation of genes to alleles with deleterious effects on survival or fertility occurs in the populations of all living organisms, and the net rate of mutation summed up over all the loci in the genome of any organism is now thought to be very high. Severely deleterious mutations are the cause of many diseases in human populations, and mutations with lesser effects are probably most important in human disease, though little is known about these as they are difficult to study. In a preliminary study, the investigators found that the occurrence of deleterious mutations in a region of the genome affects the evolution of DNA sequences in the same region. They have found that genetic variability at nucleotide sites that themselves do not affect fitness can be greatly reduced in such a region. The investigators will quantify this effect in relation to distances between the genes on the genetic map, and will extend studies to sequence differences that do have slight fitness effects. It is important in interpreting such data to include such biologically important phenomena as deleterious mutations of loci nearby in the genetic map to those under study. This has not previously been done in theoretical studies. %%% Results will have implications for the interpretation of data on variability within populations and on evolutionary divergence between populations. Such divergence in DNA sequences has b een used as a "molecular clock" to date the times of origin of species, and has also been used to infer that natural selection caused the observed differences. When other loci in the genetic background are included in the models, in addition to the loci under study, the inference of natural selection may become less certain, and that the rate of the molecular clock may prove to be influenced by the locations of genes in the genetic map, and by the level of inbreeding populations.

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