Unraveling the Impact of Genetic Mutations on Future Generations

Regarding the structure of the human genome, it is only a matter of time until detrimental genes, which have the potential to jeopardize future generations, emerge within a population.

Mutations tend to gather in the gene pool, primarily influenced by factors such as the size of a population and practices like endogamy within small communities, as indicated by researchers.

However, knowledge regarding the consequences of a population’s mutation load is grounded in genetic theory, with limited direct proof of its impact on evolutionary fitness and fertility.

In a groundbreaking study conducted by the University of California, Davis, new evidence has emerged, offering rare direct insights into how increased homozygosity, signifying the presence of two identical alleles in a genome, has adverse effects on the fertility of a human population.

This study was published on October 17^th in the Proceedings of the National Academy of Sciences journal.

People have known since Darwin that if you take people who are first cousins and they have children together, the children are more likely to develop certain diseases or be less healthy.”

Brenna Henn, Associate Professor, Anthropology, College of Letters and Science, University of California-Davis

The study investigates the implications of homozygosity within the Himba community of Namibia, an insular agro-pastoralist group where marriages between individuals sharing common ancestry are common.

This research was spearheaded by Natalie Swinford, who earned her doctoral degree in evolutionary anthropology and human population genetics in 2022, along with Henn.

They’re what we call an ‘endogamous population,’ meaning people are meeting their partners just from within that Himba group.”

Brenna Henn, Associate Professor, Anthropology, College of Letters and Science, University of California-Davis

Henn added, “They also have a unique system of marriage and reproduction, where men and women can have multiple boyfriends or girlfriends during their marriage. That means there are a lot of half-siblings in the population. That’s a unique feature and it means that we can leverage that social structure to look at different genetic effects.”

Echoes in the Genome

In the research, genetic data were collected from 681 individuals belonging to the Himba population. Through genetic analysis, it was discovered that the Himba exhibit elevated levels of inbreeding, as evidenced by specific genetic markers known as "runs of homozygosity" or ROH. These markers were not only numerous but also notably extended in the genomes of the Himba individuals under investigation, indicating a high probability that their parents shared a common ancestor.

It was intriguing to note that, despite the Himba population's historical inclination toward consanguinity, none of the individuals in the study sample had parents who were true first cousins. The lengths of the ROH within their genomes told a different story.

The researchers also observed that these genetic effects could accumulate and become more pronounced over time. Therefore, bottleneck events, such as a population decline leading to increased inbreeding, might not reveal their genetic consequences until several generations later. The study's findings pointed to the occurrence of such events within the past 12 to 18 generations within the Himba population.

People may not be full first-cousins. But they may be half-cousins once removed and then their grandparents might have been half-cousins. Anytime something like that happens, it’s going to contribute to there being identical DNA in the offspring.”

Brenna Henn, Associate Professor, Anthropology, College of Letters and Science, University of California-Davis

A Negative Effect on Fertility

The Himba community follows a pronatalist approach, actively encouraging their members to have a substantial number of children. Typically, births occur at relatively short intervals, typically spanning one to three years, according to researchers.

To assess the impact of extended runs of homozygosity (ROH) on fertility, the scientists examined the reproductive success of post-reproductive women within their study population. Reproductive success, as defined by the researchers, referred to the number of children who survived to at least five years of age.

Using statistical models, the research team investigated the relationship between the extent of ROH in an individual's genome and the number of children a woman had. Their findings indicated that as the proportion of an individual's genome affected by ROH increased, it became more likely for a woman to have fewer children in comparison to women with a lower ROH impact.

“This means that a woman who has parents who are more related is more likely to have fewer children throughout her lifetime than a woman who has parents who are less related,” stated Swinford.