This week marks the 20th anniversary of the publication of the first drafts of the Human Genome sequence. Science choose to celebrate the achievement with a series of articles that had little to say about the scientific discoveries arising out of the sequencing project; one of the articles praised the opennesss of sequence data without mentioning that the journal had violated its own policy on openness by publishing the Celera sequence [The 20th anniversary of the human genome sequence: 1. Access to the data and the complicity of Science].

I've decided to post a few articles about the human genome beginning with one on finishing the sequence. In this post I'll summarize the latest data on the number of genes in the human genome.

The first drafts of the genome sequence predicted somewhere between 30,000 and 35,000 genes based largely on software predictions. In spite of what you might have read elsewhere, this number was very close to the predictions made by knowledgeable scientists dating back to the 1970s [False history and the number of genes].

We know more about protein-coding genes than noncoding genes. The number of predicted protein-coding genes dropped steadily for about 15 years following publication of the draft sequences but it is beginning to stabilize around 19,500 genes [How many protein-coding genes in the human genome?]. That number is likely to fall to about 19,000 in the future because there are hundreds of predicted protein-coding genes that are missing a protein There will never be an exact number because some people have more genes than others.

The number of noncoding genes is still up in the air. Here's a brief summary of the most likely numbers ...

• ribosomal RNA genes: There are mutliple copies of the large ribosomal RNA operon and multiple copies of 5S RNA genes. A good estimate of the average number in a typical human genome is about 300.
• small nuclear RNAs (snRNAs) genes: Some of the main spliceosomal RNAs (U1, U2, U4, U5 and U6) are produced from a single gene but in other cases there are mutliple copies. There are a number of extra spliceosomal RNA genes such as U4atac and U7. The total number of snRNA genes is about 20.
• small nucleolar RNA (snoRNA) genes: These are genes involved in modifying ribosomal RNAs. There are more than 100 snoRNA genes.
• microRNA (miRNA) genes: Nobody knows exactly how many miRNA genes there are in the human genome. The predictions range from 100-1000 but the algorithms for detecting these genes aren't very good. It's likely that most of the predicted genes are pseudogenes. A good estimate is 100 miRNA genes.
• short interfering RNA (siRNA) genes: This is the same situation as with miRNA genes. The best guess is 100 siRNA genes.
• PIWI-interacting RNA (piRNA) genes: There are several thousand predicted piRNA genes in our genome but it's almost certain that most of them are nonfunctional. It's safe to assume there are about 100 functional genes in this category.
• long noncoding RNA (lncRNA) genes: This is an extemely heterogeneous category consisting of RNAs that are at least 1000 nucleotides in length with, in most cases, no substantial open reading frame. Some lncRNAs have a function but these are rare. It's likely that there are no more than 1000 lncRNA genes and the remaing transcripts are junk RNA.

The total number of noncoding RNA genes comes to less than 2000 but I usually feel quite generous in estimating this number so let's say that there are about 5,000. If we round up the total number of protein-coding genes to 20,000 then I'm estimating that there are no more than 25,000 genes in our genome.

Most of the sequence databases list more genes and the "extra" genes are mostly noncoding genes; for example, Ensembl estimates 23,997 noncding genes in the latest build (GRCh38.p13) [Human assembly and gene annotation]. About 17,000 of these genes are lncRNA genes but there's no evidence that these are functional genes. Until that evidence become available (I'm not holding my breath) we should stick with the best estimate of functional lncRNA genes [How many lncRNAs are functional?] [Functional RNAs?].