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Full Abstracts – EVOLUTION AND QUANTITATIVE GENETICS I
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108
A genome wide association study reveals genetic evidence of the mutation accumulation theory of aging in age-specific fecundity in
Drosophila
melanogaster
.
Mary F. Durham
1
, Michael Magwire
2
, Jeff Leips
1
. 1) Dept Biological Sci, Univ Maryland, Baltimore County, Baltimore, MD; 2) Department
of Genetics, N.C. State University, Raleigh, NC.
Senescence is a phenomenon experienced by virtually all organisms and despite decades of research on a myriad of species and age-related diseases,
mechanisms of aging remain poorly understood, especially at the genetic level. Evolutionary theories of aging are centered on lifespan and reproduction
since organisms must survive long enough to reproduce in order to contribute alleles to subsequent generations and thereby maintain alleles that influence
senescence in a population. Additionally, senescence is often believed to be due to trade-offs between lifespan and fecundity or early-age vs. late-age
fecundity. Although it is clear that lifespan and age-specific fecundity are genetically controlled, the specific genes influencing natural variation in these
traits and their relationship with each other, as well as their influences on aging are largely unknown. The goal of this work was to identify genes influencing
mated lifespan and age-specific fecundity in
Drosophila melanogaster
. To do this we completed a genome wide association study (GWAS) using the
Drosophila
Genome Reference Panel (DGRP) to reveal candidate genes affecting these traits. We quantified lifespan as days lived and estimated age-
specific fecundity as a two-day egg total every other week for each female until death. Our results indicate that there is extensive natural genetic variation in
lifespan and age-specific reproduction. We identified over 2000 candidate single nucleotide polymorphisms (SNPs) involved in lifespan and age-specific
fecundity. Our data also provide solid support for the mutation accumulation theory of aging as we see a significant increase in the number of genes
contributing to variation in fecundity with increasing age. These results shed light on our understanding of the genetic mechanisms that drive lifespan, age-
specific fecundity and senescence.
109
Strong Purifying Selection at Synonymous Sites in
D. melanogaster
.
David S. Lawrie
1
, Philipp W. Messer
2
, Ruth Hershberg
3
, Dmitri A. Petrov
2
. 1) Dept.
of Genetics, Stanford University, Stanford, CA; 2) Dept. of Biology, Stanford University, Stanford, CA; 3) The Ruth and Burce Rappaport Faculty of
Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Synonymous sites are generally assumed to be subject to weak selective constraint. For this reason, they are often neglected as a possible source of
important functional variation. We use site frequency spectra from deep population sequencing data to show that contrary to this expectation a substantial
proportion of synonymous sites in
D. melanogaster
evolve under very strong selective constraint while few, if any, synonymous sites appear to be under
weak constraint. Linking polymorphism with divergence data, we further find that the proportion of synonymous sites exposed to strong purifying selection
is higher for those positions that show slower evolution on the Drosophila phylogeny. However, fewer synonymous sites are conserved across the entire tree
than expected given the estimated percentage of strongly constrained sites. Together, these results suggest that the strong constraint at synonymous sites is
episodic, such that any particular position may spend part of its evolutionary history evolving under tight constraint and part evolving neutrally or almost
neutrally. This model of episodic strong selection appears to explain the rates of evolution of synonymous sites better than the alternative model of consistent
weak selection.
110
Small-scale Hitchhiking Effects in
Drosophila
.
Grace Y C Lee, David J Begun, Charles H Langley. Ctr Population Biol, Univ California, Davis, Davis,
CA.
Accumulated evidence suggests that beneficial substitutions are common in
Drosophila
. Selective fixation of initially rare alleles leads to a transient
reduction of nearby neutral genetic variation, a phenomenon known as “genetic hitchhiking” or “selective sweep”. The physical extent and magnitude of
reduced variation depends on the intensity of selection and the time since fixation of the favored variants. Previous estimates of selection coefficient for
weakly beneficial mutations suggested that the extent of selective sweep of these prevalent variants is expected to be within hundreds of base pairs, which
may play an important role in the overall genome-wide pattern of polymorphism. Here, we used the population genomic data of
D. melanogaster
and
D.
simulans
, two species that have similar geographic distribution and demographic histories yet significantly different patterns of genetic variation, to examine
the extent of small-scale (several hundreds to a few thousands of base pairs) genetic hitchhiking around substitutions in regions with high recombination.
Our preliminary analysis found variants fixed from ancestral polymorphism show a weaker reduction in nearby neutral polymorphism than those that are not.
Surprisingly, amino acid fixations at sites that substituted multiple times over the phylogeny showed stronger hitchhiking effects than those at sites that are
highly conserved. We also observed substitutions leading to changes in amino acid polarities or charges have different levels of trough in neighboring
diversity. Although selection for codon bias is generally viewed as a weak selective force, especially in
D. melanogaster
, its effect on variation reduction is
readily detectable. We will also present similar analyses from noncoding regions.