Research Projects
Dr. Makova is interested in molecular evolution,
population genetics, evolutionary genomics, bioinformatics, and
human genetics. The laboratory employs a combination of molecular
and computational approaches. Some of the current projects include:
- Male mutation bias, or male-driven
evolution. As the number of cell
divisions is higher in the male germ line compared to the female
germ line, the number of mutations originating in males is also
higher than in females. The underlying assumption is that mutations
are replication-driven. Y chromosome mutates faster than X, while
autosomes have intermediate mutation rate. This is because Y
is carried only by males, autosomes spend equal amount of time
in males and females, and X spends 1/3 of time in males and 2/3
of time in females. Thus, by studying mutations on different
types of chromosomes, one can investigate the male-to-female
mutation rate ratio. The research focuses on estimating the male-to-female
mutation rate ratio for different types of mutations (nucleotide
substitutions, insertions and deletions, changes in the microsatellite
repeat number) and for different organisms (primates, rodents
as well as other mammals). This project is critical for genetic
counseling (how important is the age of a male at the time of
reproduction?) as well as for our understanding of mutation mechanisms.
- Evolution of gene expression.
While we now have some information
about the evolution of the protein coding genes, there is a paucity
of knowledge about evolution of gene expression. For instance,
does the divergence in gene expression correlate with the protein
sequence divergence? In other words, are the evolution of coding
region and the evolution of mRNA expression coupled? One can
have some insight into this question by analyzing the tempo of
expression divergence between duplicate genes in a genome. A
general picture is now achievable thanks to the advent of microarray
gene expression technology and the complete sequences of many
genomes. Another area of interest is population genetics and
molecular evolution of promoters.
- Human population genomics.
With the completion of the Human
Genome Project, it is possible to study human population genetics
on a whole-genome scale. Such approach is more robust compared
with the earlier single locus studies. Specific questions include
detecting positive selection and studying patterns of linkage
disequilibrium. Population genetics and molecular evolution of
genes important for human skin pigmentation are of particular
interest. The results of this investigation will provide direct
information on the usefulness of particular populations and of
particular genetic polymorphisms for disease gene identification
studies. This project is pursued in collaboration with Dr. Mark
Shriver from the Anthropology Department.