Dear all,
just a gentle reminder the next seminar will take place this
Wednesday, the details are below. We look forward to seeing you all.
Best wishes,
Petr Danecek
---------------------------------
Title: Investigating the Genetics of
Sexual Reproduction in 200,000 Humans
Speaker: Eugene Gardner
Date and time: Wednesday 23/03/2022 - 17:20
Location: MFF UK, Malostranské nám. 25, lecture hall S9
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.