Peter Kerpedjiev needed a crash course in genetics. A software engineer with some training in bioinformatics, he was pursuing a PhD and thought it would really help to know some fundamentals of biology. “If I wanted to have an intelligent conversation with someone, what genes do I need to know about?” he wondered.

Kerpedjiev went straight to the data. For years, the US National Library of Medicine (NLM) has been systematically tagging almost every paper in its popular PubMed database that contains some information about what a gene does. Kerpedjiev extracted all the papers marked as describing the structure, function or location of a gene or the protein it encodes.

Sorting through the records, he compiled a list of the most studied genes of all time — a sort of ‘top hits’ of the human genome, and several other genomes besides.

Heading the list, he found, is a gene called TP53. Three years ago, when Kerpedjiev first did his analysis, researchers had scrutinized the gene or the protein it produces, p53, in some 6,600 papers. Today, that number is at about 8,500 and counting. On average, around two papers are published each day describing new details of the basic biology of TP53.

Its popularity shouldn’t come as news to most biologists. The gene is a tumour suppressor, and widely known as the ‘guardian of the genome’. It is mutated in roughly half of all human cancers. “That explains its staying power,” says Bert Vogelstein, a cancer geneticist at the Johns Hopkins University School of Medicine in Baltimore, Maryland. In cancer, he says, “there’s no gene more important”.

But some chart-topping genes are less well known — including some that rose to prominence in bygone eras of genetic research, only to fall out of fashion as technology progressed. “The list was surprising,” says Kerpedjiev, now a postdoc studying genomic-data visualization at Harvard Medical School in Boston, Massachusetts. “Some genes were predictable; others were completely unexpected.”

The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome and the mitochondrial genome. Human genomes include both protein-coding DNA genes and noncoding DNA. Haploid human genomes, which are contained in germ cells (the egg and sperm gamete cells created in the meiosis phase of sexual reproduction before fertilization creates a zygote) consist of 3 055 000 000 DNA base pairs, while diploid genomes (found in somatic cells) have twice the DNA content. While there are significant differences among the genomes of human individuals (on the order of 0.1% due to single-nucleotide variants and 0.6% when considering indels), these are considerably smaller than the differences between humans and their closest living relatives, the bonobos and chimpanzees (~1.1% fixed single-nucleotide variants and 4% when including indels).

Although the sequence of the human genome has been completely determined by DNA sequencing,

In 2003, scientists reported the sequencing 85% of the entire human genome.

In 2022, scientists reported sequencing the complete female genome. This sequence identified 19,969 protein-coding sequences, accounting for approximately 1.5% of the genome, and 63,494 genes in total, most of them being non-coding RNA genes. genome consists of regulatory DNA sequences, LINEs, SINEs, introns, and sequences for which as yet no function has been determined. The human Y chromosome containing 53 000 000 base pairs, and found in all men, has not yet been sequenced completely.

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