Dear all,
please be sure to mark your calendars for the next lecture in our
invited speakers series.
Our guest will be Eugene Gardner, a postdoctoral research
associate at Trinity Hall in Cambridge, and he will present his
most recent work on Wednesday 23/03/2022 at 17:20 at
Malostranské náměstí. The lecture hall will be announced later.
Please see the details below.
Best wishes,
Petr Danecek
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Speaker: Eugene Gardner
Title: Investigating the Genetics
of Sexual Reproduction in 200,000 Humans
Abstract: Why genes in the human genome are
under significant constraint remains a mystery. New genetic
variants arise in the germline due to mutation. While the
majority are genetically neutral and have no effect on
phenotype, some variants confer either an advantage and proceed
towards fixation via positive selection, or a disadvantage and
are removed from the gene pool by negative selection. The
context of where a given variant arises in the genome strongly
predicts whether it is eliminated or becomes fixed, with the
function of the gene impacted among the most predictive for
coding variation. Genes that are depleted of deleterious genetic
variation (DGV) due to negative selection are said to be
“constrained”. Depending on the method of calculation and
dataset used, the human genome contains ~3,000 such genes. While
genes associated with dominant diseases such as developmental
disorders are among the most constrained genes in the human
genome, well-characterised gene-disease pairs only comprise ~35%
of all genes determined to be under significant constraint.
Based on the principles of evolution, it can be assumed that
natural selection shapes genic constraint by reducing an
individual’s ability to pass on their genes via sexual
reproduction. As part of recent work, using sequencing data for
200,000 humans from the UK Biobank Study, we have shown that
genetic variants that damage these genes are associated with
markedly reduced reproductive success, primarily due to
increased childlessness, with a stronger effect in males than in
females. We provided evidence that increased childlessness is
likely mediated by genetically associated cognitive and
behavioural traits, which may mean male carriers are less likely
to find reproductive partners. This reduction in reproductive
success may account for 20% of purifying selection against
heterozygous variants that ablate protein-coding genes. While
this genetic association could only account for a very minor
fraction of the overall likelihood of being childless (less than
1%), especially when compared to more influential
sociodemographic factors, it may influence how genes evolve over
time.