Number of protein-coding genes. About 20,000 human proteins have been annotated in databases such as Uniprot. Historically, estimates for the number of protein genes have varied widely, ranging up to 2,000,000 in the late 1960s, but several researchers pointed out in the early 1970s that the estimated mutational load from deleterious mutations placed an upper limit of approximately 40,000 for the total number of functional loci (this includes protein-coding and functional non-coding genes). The number of human protein-coding genes is not significantly larger than that of many less complex organisms, such as the roundworm and the fruit fly. This difference may result from the extensive use of alternative pre-mRNA splicing in humans, which provides the ability to build a very large number of modular proteins through the selective incorporation of exons.