Living Columns & Blogs

How many genes does it take to make a person?

Editor’s note: The Focus on Research column highlights different research projects and topics being explored at Penn State. Each column will feature the work of a different researcher from across all disciplines. The following is the first of a two-part installment that originally appeared on The Conversation.

We humans like to think of ourselves as on the top of the heap compared to all other living things on the planet. Life has evolved over 3 billion years from simple one-celled creatures through to multicellular plants and animals coming in all shapes and sizes and abilities. In addition to growing ecological complexity, over the history of life we’ve also seen the evolution of intelligence, complex societies and technological invention, until we arrive today at people flying around the world at 35,000 feet discussing the in-flight movie.

It’s natural to think of the history of life as progressing from the simple to the complex, and to expect this to be reflected in increasing gene numbers. We fancy ourselves leading the way with our superior intellect and global domination; the expectation was that because we’re the most complex creature, we’d have the most elaborate set of genes.

This presumption seems logical, but the more researchers figure out about various genomes, the more flawed it seems. About a half-century ago the estimated number of human genes was in the millions. Today we’re down to about 20,000.

As researchers devise new ways to count not just the genes an organism has, but also the ones it has that are superfluous, there’s a clear convergence between the number of genes in what we’ve always thought of as the simplest lifeforms — viruses — and the most complex — us. It’s time to rethink the question of how the complexity of an organism is reflected in its genome.

Counting up the genes

We can think of all our genes together as the recipes in a cookbook for us. They’re written in the letters of the bases of DNA — abbreviated as ACGT. The genes provide instructions on how and when to assemble the proteins that you’re made of and that carry out all the functions of life within your body. A typical gene requires about 1,000 letters. Together with the environment and experience, genes are responsible for what and who we are — so it’s interesting to know how many genes add up to a whole organism.

When we’re talking about numbers of genes, we can display the actual count for viruses, but only the estimates for human beings for an important reason. One challenge counting genes in eukaryotes — which include us, bananas and yeast like Candida — is that our genes are not lined up like ducks in a row.

Our genetic recipes are arranged as if the cookbook’s pages have all been ripped out and mixed up with three billion other letters, about 50 percent of which actually describe inactivated, dead viruses. So in eukaryotes it’s hard to count up the genes that have vital functions and separate them from what’s extraneous.

Flourishing with even fewer

The number of genes we need for a healthy life is probably even lower than the current estimate of 20,000 in our entire genome. One author of a recent study has reasonably extrapolated that the count for essential genes for human beings may be much lower.

These researchers looked at thousands of healthy adults, looking for naturally occurring “knockouts,” in which the functions of particular genes are absent. All our genes come in two copies — one from each parent. Usually, one active copy can compensate if the other is inactive, and it is difficult to find people with both copies inactivated because inactivated genes are naturally rare.

Knockout genes are fairly easy to study with lab rats, using modern genetic engineering techniques to inactivate both copies of particular genes of our choice, or even remove them altogether, and see what happens. But human studies require populations of people living in communities with 21st century medical technologies and known pedigrees suited to the genetic and statistical analyses required. Icelanders are one useful population, and the British-Pakistani people of this study are another.

This research found more than 700 genes which can be knocked out with no obvious health consequences. For instance, one surprising discovery was that the PRDM9 gene — which plays a crucial role in the fertility of mice — can also be knocked out in people with no ill effects.

Extrapolating the analysis beyond the human knockouts study leads to an estimate that only 3,000 human genes are actually needed to build a healthy human. This is in the same ballpark as the number of genes in “giant viruses.” Pandoravirus, recovered from 30,000-year-old Siberian ice in 2014, is the largest virus known to date and has 2,500 genes.

So what genes do we need? We don’t even know what a quarter of human genes actually do, and this is advanced compared to our knowledge of other species.

Sean Nee is a research professor of ecosystem science and management at Penn State.